Clinical Clinical PharmacologyPharmacologybreast cancer breast cancer byby

DrWaleed ElnahasDrWaleed ElnahasLecturer of surgical oncologyLecturer of surgical oncology

Hosam ElghadbanHosam ElghadbanAssistant Lecturer of surgeryAssistant Lecturer of surgery

IncidenceIncidence Age- Age- 40-50 yr 40-50 yr

NO age is immuneNO age is immune after puberty after puberty

Sex- Sex-

= 991 = 991 (the commonest tumor in female)(the commonest tumor in female)

Side- Side-

Left gt right Left gt right

Bilateral-----raquo Simultaneous Bilateral-----raquo Simultaneous 11

-----raquo Metachronous -----raquo Metachronous 55

Site- Site-

Upper outer quadrant 60 -----raquo most of mammary Upper outer quadrant 60 -----raquo most of mammary tissue tissue

Geographic- Geographic-

West West gt east gt east

Developed gt Developed gt developing developing

Etiology Etiology (predisposing factors)(predisposing factors)

1-Genetic1-Genetic

A-Young age lt 30 yrA-Young age lt 30 yr

b- Mostly Bilateralb- Mostly Bilateral

c- Multiple relatives with cancer breast (gt3) c- Multiple relatives with cancer breast (gt3)

-Hereditary breast cancer 5ndash10-Hereditary breast cancer 5ndash10 BRCA-1 BRCA-1 Long arm of chromosome 17qLong arm of chromosome 17q BRCA-2 BRCA-2 Long arm of chromosome 13qLong arm of chromosome 13q Li-Fraumeni syndrome P53 Li-Fraumeni syndrome P53 Short arm chromosome Short arm chromosome

17p17p

2- Endocrinal (Hormonal)2- Endocrinal (Hormonal)

- Not married null Para elderly primigravida - Not married null Para elderly primigravida (gt 35 yr) and non-lactating female (gt 35 yr) and non-lactating female

- Early menarche or late menopause due to - Early menarche or late menopause due to prolonged exposure to estrogenprolonged exposure to estrogen

3- Exposure to radiation3- Exposure to radiation

- Nuclear war - Nuclear war

- Medical purposes (diagnostic or therapeutic - Medical purposes (diagnostic or therapeutic being greater for exposures in childhood and being greater for exposures in childhood and adolescence than after age of 40 years)adolescence than after age of 40 years)

4-drugs estrogen contraceptive pills more 4-drugs estrogen contraceptive pills more than 10 years (uncertain)than 10 years (uncertain)

pathologypathology World Health Organization Classification of World Health Organization Classification of

Carcinoma of the Breast Carcinoma of the Breast Noninvasive carcinomaNoninvasive carcinoma

-Ductal carcinoma -Ductal carcinoma in situin situ -Lobular carcinoma -Lobular carcinoma in situin situ Invasive carcinomaInvasive carcinoma

-Invasive ductal carcinoma -- 80-Invasive ductal carcinoma -- 80

-Invasive lobular carcinoma ndash 10-Invasive lobular carcinoma ndash 10

-Mucinous carcinoma -- 2-Mucinous carcinoma -- 2

-Medullary carcinoma ndash 5-Medullary carcinoma ndash 5

-Papillary carcinoma -- 1-Papillary carcinoma -- 1

-Tubular carcinoma ndash 1-Tubular carcinoma ndash 1

-Adenoid cystic carcinoma-Adenoid cystic carcinoma

-Secretory (juvenile) carcinoma-Secretory (juvenile) carcinoma

-Apocrine carcinoma-Apocrine carcinoma

-Carcinoma with metaplasia (metaplastic carcinoma)-Carcinoma with metaplasia (metaplastic carcinoma)

-Inflammatory carcinoma-Inflammatory carcinoma

-Other sarcoma lymphoma and melanoma-Other sarcoma lymphoma and melanoma Pagets disease of the nipplePagets disease of the nipple

SpreadSpreadDirect spread-Direct spread-

11 Intrinsic Intrinsic to surrounding breast tissue to surrounding breast tissue

2 2 ExtrinsicExtrinsic

To the skin causing ulceration amp To the skin causing ulceration amp fungation fungation

To deep structures Pectoral fascia To deep structures Pectoral fascia pectoral muscles amp chest wallpectoral muscles amp chest wall

Lymphatic spread-Lymphatic spread-

Haematogenous spread- Haematogenous spread-

Transcoelomic spread-Transcoelomic spread-

Clinical pictureClinical picture Symptoms Symptoms

A- AsymptomaticA- Asymptomatic- - discovered discovered accidentally during screening programs accidentally during screening programs

B- SymptomaticB- Symptomatic- -

1 Mass 1 Mass ((commonest presentationcommonest presentation) )

2 Pain2 Pain ( (Very Rare 10Very Rare 10))

3 Nipple discharge 3 Nipple discharge - Bloody discharge - Bloody discharge in duct carcinoma in duct carcinoma

4 Skin amp nipple manifestations4 Skin amp nipple manifestations

5 Manifestations of metastasis- 5 Manifestations of metastasis-

Signs Signs

A) General examinationsA) General examinations

1 Chest signs of pleural effusion or 1 Chest signs of pleural effusion or mediastinal LNmediastinal LN

2 Abdominal examination2 Abdominal examination

- Hepatomegaly - Ascites- Hepatomegaly - Ascites

3 PR or PV nodules in the 3 PR or PV nodules in the Douglasrsquo pouch or Krukenbergrsquos Douglasrsquo pouch or Krukenbergrsquos tumortumor

4 Bone for tenderness swelling amp 4 Bone for tenderness swelling amp pathological fracturepathological fracture

B) Local examinationB) Local examination

1- inspection1- inspection

BreastBreast compared to healthy side compared to healthy side

Nipple amp areola Nipple amp areola may showmay show

the skinthe skin

1) Skin dimpling Tethering amp Puckering1) Skin dimpling Tethering amp Puckering

2) ulceration amp fungation 2) ulceration amp fungation

3) Peau drsquoorange (Pitted edema) 3) Peau drsquoorange (Pitted edema)

4) Cancerous satellite nodules (late sign) 4) Cancerous satellite nodules (late sign)

5) Cancer en cuirasse5) Cancer en cuirasse

The massThe mass the axillathe axilla The armThe arm

2- palpation2- palpation palpate breasts with both the flat of your palpate breasts with both the flat of your

hand and fingers hand and fingers with flat fingers compress breast tissue with flat fingers compress breast tissue follow systematically in a circular follow systematically in a circular

pattern around the nipple or along the pattern around the nipple or along the radial lines (simulate a clock) or vertical radial lines (simulate a clock) or vertical segments and feel the entire breast segments and feel the entire breast including the tail near the axillaincluding the tail near the axilla

Examine criteria of the mass site size shape consistency

Examine axillary lymph nodes

American Joint Committee on Cancer TNM Staging System for Breast American Joint Committee on Cancer TNM Staging System for Breast Cancer Cancer

Primary Tumor (T)Primary Tumor (T) TX Primary tumor cannot be assessedTX Primary tumor cannot be assessed T0 No evidence of primary tumorT0 No evidence of primary tumor Tis Carcinoma Tis Carcinoma in situin situ

Note Pagets disease associated with a tumor is classified according Note Pagets disease associated with a tumor is classified according to the size of the tumor to the size of the tumor

T1 Tumor 2 cm or less in greatest dimensionT1 Tumor 2 cm or less in greatest dimension

T1mic Microinvasion 01 cm or less in greatest dimensionT1mic Microinvasion 01 cm or less in greatest dimension

T1a Tumor more than 01 cm but not more than 05 cm in greatest T1a Tumor more than 01 cm but not more than 05 cm in greatest dimension dimension

T1b Tumor more than 05 cm but not more than 1 cm in greatest T1b Tumor more than 05 cm but not more than 1 cm in greatest dimension dimension

T1c Tumor more than 1 cm but not more than 2 cm in greatest T1c Tumor more than 1 cm but not more than 2 cm in greatest dimensiondimension

T2 Tumor more than 2 cm but not more than 5 cm in greatest T2 Tumor more than 2 cm but not more than 5 cm in greatest dimensiondimension

T3 Tumor more than 5 cm in greatest dimensionT3 Tumor more than 5 cm in greatest dimension T4a Extension to chest wall not including pectoralis muscleT4a Extension to chest wall not including pectoralis muscle

T4b Edema (including peau dorange) or ulceration of the skin of the T4b Edema (including peau dorange) or ulceration of the skin of the breast or satellite skin nodules confined to the same breast breast or satellite skin nodules confined to the same breast

T4c Both T4a and T4bT4c Both T4a and T4b

T4d Inflammatory carcinomaT4d Inflammatory carcinoma

Regional Lymph Nodes (N) Regional Lymph Nodes (N) NX Regional lymph nodes cannot be assessed (eg NX Regional lymph nodes cannot be assessed (eg

previously removed) previously removed) N0 No regional lymph node metastasisN0 No regional lymph node metastasis N1 Metastasis to movable ipsilateral axillary lymph N1 Metastasis to movable ipsilateral axillary lymph

node(s)node(s) N2 N2

N2a Metastases in ipsilateral axillary lymph nodes N2a Metastases in ipsilateral axillary lymph nodes fixed to one another (matted) or to other structures fixed to one another (matted) or to other structures

N2b Metastasis only in N2b Metastasis only in clinically apparentclinically apparent ipsilateral ipsilateral internal mammary nodes and in theinternal mammary nodes and in the absence absence of of clinically evident axillary lymph node metastasis clinically evident axillary lymph node metastasis

N3N3

N3a Metastasis in ipsilateral infraclavicular lymph N3a Metastasis in ipsilateral infraclavicular lymph node(s)node(s)

N3b Metastasis in ipsilateral internal mammary N3b Metastasis in ipsilateral internal mammary lymph node(s) and axillary lymph node(s) lymph node(s) and axillary lymph node(s)

N3c Metastasis in ipsilateral supraclavicular lymph N3c Metastasis in ipsilateral supraclavicular lymph node(s)node(s)

M ( METASTASIS)M ( METASTASIS)

MX metastasis can no be assessedMX metastasis can no be assessed

M0 no metastasisM0 no metastasis

M1 metastasisM1 metastasis

American Cancer SocietyAmerican Cancer SocietyScreening RecommendationsScreening Recommendations

Annual mammogramsAnnual mammograms starting at starting at age 40age 40

Clinical breast examsClinical breast examsndash every year starting at age 40every year starting at age 40ndash every 3 years for women age every 3 years for women age 20-3920-39

Self-breast examsSelf-breast exams monthly starting monthly starting at age 20at age 20

Breast Self-Exam ndash Step Breast Self-Exam ndash Step 11 Begin by looking at your breasts in the mirror Begin by looking at your breasts in the mirror

with your shoulders straight and yourwith your shoulders straight and your

arms on your hipsarms on your hips Heres what you should look forHeres what you should look for

Breasts that are their usual size shape and colorBreasts that are their usual size shape and color

--Breasts that are evenly shaped without visible --Breasts that are evenly shaped without visible distortion or swellingdistortion or swelling

If you see any of the following changes bring If you see any of the following changes bring them to your doctors attentionthem to your doctors attention

--Dimpling puckering or bulging of the skin--Dimpling puckering or bulging of the skin

--A nipple that has changed position or become --A nipple that has changed position or become inverted (pushed inward instead ofinverted (pushed inward instead of

sticking out)sticking out) --Redness soreness rash or swelling--Redness soreness rash or swelling

Breast Self-Exam ndash Step Breast Self-Exam ndash Step 22

Raise your arms and look for the Raise your arms and look for the

samesame

changeschanges

Breast Self-Exam ndash Step Breast Self-Exam ndash Step 33 Feel your breasts while lying down using Feel your breasts while lying down using

your right hand to feel your left breast and your right hand to feel your left breast and then your left hand to feel your right breast then your left hand to feel your right breast Use a firm smooth touch with the first few Use a firm smooth touch with the first few fingers of your hand keeping the fingersfingers of your hand keeping the fingers

flat and togetherflat and together

Cover the entire breast from top to Cover the entire breast from top to bottom side to sidemdashfrom your bottom side to sidemdashfrom your collarbone to the top of your abdomen collarbone to the top of your abdomen and from your armpit to your cleavageand from your armpit to your cleavage

Breast Self-Exam ndash Step Breast Self-Exam ndash Step 44

Finally feel your breasts while you are Finally feel your breasts while you are standing or sitting Many women find standing or sitting Many women find that the easiest way to feel their breasts that the easiest way to feel their breasts is when their skin is wet and slippery is when their skin is wet and slippery so they like to do this step in the so they like to do this step in the shower Cover your entire breast using shower Cover your entire breast using the same hand movements described in the same hand movements described in Step 3Step 3

InvestigationsInvestigations

Mammography (conrsquot)Mammography (conrsquot) 1048698 1048698 Standard mammography Standard mammography depends on depends on

density of the tissue and its ability to stop density of the tissue and its ability to stop xrayxray

beam from exposing film placed on the other beam from exposing film placed on the other side of the breastside of the breast

Digital mammography Digital mammography works on the same works on the same principle but there is also some ability to principle but there is also some ability to manipulate the image by computer Main manipulate the image by computer Main advantage is storage of the filmsadvantage is storage of the films

UltrasoundUltrasound

Since solid tissue andSince solid tissue and collections of fluid look thecollections of fluid look the same on mammographysame on mammography ultrasound is very useful in ultrasound is very useful in telling whether a mass istelling whether a mass is solid or fluid and if solid ifsolid or fluid and if solid if characteristics arecharacteristics are suspicioussuspicious CystCyst

MRIMRI MRI relies on completely different type of MRI relies on completely different type of

wavewave

energy a strong magnet that affects the energy a strong magnet that affects the charge incharge in

the nuclei As magnetic force is applied and the nuclei As magnetic force is applied and thenthen

released different types of tissue send back released different types of tissue send back different types of radio wavesdifferent types of radio waves

MRI can be extremely useful in very denseMRI can be extremely useful in very dense

breasts hereditary casesbreasts hereditary cases

Fine needle aspiration of a palpable mass

1048698 Fine needle aspiration takes individual cells out ofmass Can be done for palpable or non-palpablemasses Does not show architecture especially wallof duct so best used to confirm strong suspicions

Fine Needle Aspiration

C0 No epithelial cellsC1 InadequateC2 BenignC3 AtypiaC4 SuspiciousC5 Malignant

1048698 Core biopsy can also bedone on palpable and non palpableabnormalities and on microcalcifications

Core Biopsy

B1 Normal tissue unsatisfactoryB2 BenignB3 Lesion uncertain malignant potentialB4 Suspicion of malignancyB5a In situ malignancyB5b Invasive malignancy

Investigations for Investigations for metastasismetastasis

1- abdominal ultrasound1- abdominal ultrasound

2- chest x ray or CT2- chest x ray or CT

3- bone survey or bone scan3- bone survey or bone scan

Established prognostic Established prognostic factorsfactors

bull Nodal status Nodal status bull Tumor size Tumor size bull Lymph node Lymph node bull Grade Grade bull ERPR StatusERPR Statusbull Age Age bull Lymphatic invasionLymphatic invasionbull Histological tumor typeHistological tumor type bull Perinodular infiltrationPerinodular infiltration

TREATMENT OPTIONS FOR PRIMARY OPERABLE BREAST CANCER Objective Options

Local control Lumpectomy Lumpectomy with breast irradiation Mastectomy

Regional control Axillary lymph node dissection Regional irradiation

Control of occult Chemotherapymicrometastatic disease Hormone therapy

Improved function and cosmesis Breast-conserving therapy Reconstruction (immediate or delayed)

Localized breast cancer Surgery is mainstay Halsted 1882 radical mastectomy

John Hopkins

Metastatic breast cancer Systemic treatment

Radical mastectomy A Entire breast and a

chest wall muscle is removed

LNs in the level 1 (B) and level 2 (C ) and even sometimes more distant lymph node groups (D E and F) were also removed

Modified radical mastectomy (MRM)

A Entire breast is removed

Classically some lymph nodes in the level 1 (B) and level 2 (C ) were removed called an axillary lymph node dissection

MRM = simple mastectomy + ALND

Breast conserving surgery

Also called lumpectomy with safety margin with axillary clearance or sentinel lymph node biopsy

RT should be followed

Adjuvant systemic treatment

Hypothesis Eradicate micrometastasis From effective treatment for overt

(macro) metastasis

Chemotherapy Hormone therapy

Adjuvant chemotherapy

CMF first generation 1970s Cyclophosphamide Methotrexate 5-FU

Benefit in Distant recurrence Survival

Adjuvant chemotherapy

CAF or CEF 2nd generation 1980s Cyclophophamide Adramycin(or Epirubicin) 5-FU

More toxic than CMF CAF better than CMF in high-risk group

Axilla LN+ LN- but tumor large or other risk factor

Adjuvant chemotherapy

Incorporate Taxane TAC 3rd generation mid-1990s

Taxotere Adriamycin Cyclophosphamide

More toxic than CAF Better than CAF in high-risk group

Need more time to observe

Adjuvant Herceptin(HER-2 (Human Epidermal growth factor Receptor 2) also

known as proto-oncogene Neu Over expression of this gene is correlated with higher aggressiveness in breast cancer

HER2 is a cell membrane surface-bound receptor tyrosine kinase and is normally involved in the signal transduction pathways leading to cell growth and differentiation)

Effective in Her2+ pts ICH3+ FISH+

Herceptin + adjuvant chemotherapy Optimal role to be defined

Concurrent or sequential Maintenance Duration

IncidenceIncidence Age- Age- 40-50 yr 40-50 yr

NO age is immuneNO age is immune after puberty after puberty

Sex- Sex-

= 991 = 991 (the commonest tumor in female)(the commonest tumor in female)

Side- Side-

Left gt right Left gt right

Bilateral-----raquo Simultaneous Bilateral-----raquo Simultaneous 11

-----raquo Metachronous -----raquo Metachronous 55

Site- Site-

Upper outer quadrant 60 -----raquo most of mammary Upper outer quadrant 60 -----raquo most of mammary tissue tissue

Geographic- Geographic-

West West gt east gt east

Developed gt Developed gt developing developing

Etiology Etiology (predisposing factors)(predisposing factors)

1-Genetic1-Genetic

A-Young age lt 30 yrA-Young age lt 30 yr

b- Mostly Bilateralb- Mostly Bilateral

c- Multiple relatives with cancer breast (gt3) c- Multiple relatives with cancer breast (gt3)

-Hereditary breast cancer 5ndash10-Hereditary breast cancer 5ndash10 BRCA-1 BRCA-1 Long arm of chromosome 17qLong arm of chromosome 17q BRCA-2 BRCA-2 Long arm of chromosome 13qLong arm of chromosome 13q Li-Fraumeni syndrome P53 Li-Fraumeni syndrome P53 Short arm chromosome Short arm chromosome

17p17p

2- Endocrinal (Hormonal)2- Endocrinal (Hormonal)

- Not married null Para elderly primigravida - Not married null Para elderly primigravida (gt 35 yr) and non-lactating female (gt 35 yr) and non-lactating female

- Early menarche or late menopause due to - Early menarche or late menopause due to prolonged exposure to estrogenprolonged exposure to estrogen

3- Exposure to radiation3- Exposure to radiation

- Nuclear war - Nuclear war

- Medical purposes (diagnostic or therapeutic - Medical purposes (diagnostic or therapeutic being greater for exposures in childhood and being greater for exposures in childhood and adolescence than after age of 40 years)adolescence than after age of 40 years)

4-drugs estrogen contraceptive pills more 4-drugs estrogen contraceptive pills more than 10 years (uncertain)than 10 years (uncertain)

pathologypathology World Health Organization Classification of World Health Organization Classification of

Carcinoma of the Breast Carcinoma of the Breast Noninvasive carcinomaNoninvasive carcinoma

-Ductal carcinoma -Ductal carcinoma in situin situ -Lobular carcinoma -Lobular carcinoma in situin situ Invasive carcinomaInvasive carcinoma

-Invasive ductal carcinoma -- 80-Invasive ductal carcinoma -- 80

-Invasive lobular carcinoma ndash 10-Invasive lobular carcinoma ndash 10

-Mucinous carcinoma -- 2-Mucinous carcinoma -- 2

-Medullary carcinoma ndash 5-Medullary carcinoma ndash 5

-Papillary carcinoma -- 1-Papillary carcinoma -- 1

-Tubular carcinoma ndash 1-Tubular carcinoma ndash 1

-Adenoid cystic carcinoma-Adenoid cystic carcinoma

-Secretory (juvenile) carcinoma-Secretory (juvenile) carcinoma

-Apocrine carcinoma-Apocrine carcinoma

-Carcinoma with metaplasia (metaplastic carcinoma)-Carcinoma with metaplasia (metaplastic carcinoma)

-Inflammatory carcinoma-Inflammatory carcinoma

-Other sarcoma lymphoma and melanoma-Other sarcoma lymphoma and melanoma Pagets disease of the nipplePagets disease of the nipple

SpreadSpreadDirect spread-Direct spread-

11 Intrinsic Intrinsic to surrounding breast tissue to surrounding breast tissue

2 2 ExtrinsicExtrinsic

To the skin causing ulceration amp To the skin causing ulceration amp fungation fungation

To deep structures Pectoral fascia To deep structures Pectoral fascia pectoral muscles amp chest wallpectoral muscles amp chest wall

Lymphatic spread-Lymphatic spread-

Haematogenous spread- Haematogenous spread-

Transcoelomic spread-Transcoelomic spread-

Clinical pictureClinical picture Symptoms Symptoms

A- AsymptomaticA- Asymptomatic- - discovered discovered accidentally during screening programs accidentally during screening programs

B- SymptomaticB- Symptomatic- -

1 Mass 1 Mass ((commonest presentationcommonest presentation) )

2 Pain2 Pain ( (Very Rare 10Very Rare 10))

3 Nipple discharge 3 Nipple discharge - Bloody discharge - Bloody discharge in duct carcinoma in duct carcinoma

4 Skin amp nipple manifestations4 Skin amp nipple manifestations

5 Manifestations of metastasis- 5 Manifestations of metastasis-

Signs Signs

A) General examinationsA) General examinations

1 Chest signs of pleural effusion or 1 Chest signs of pleural effusion or mediastinal LNmediastinal LN

2 Abdominal examination2 Abdominal examination

- Hepatomegaly - Ascites- Hepatomegaly - Ascites

3 PR or PV nodules in the 3 PR or PV nodules in the Douglasrsquo pouch or Krukenbergrsquos Douglasrsquo pouch or Krukenbergrsquos tumortumor

4 Bone for tenderness swelling amp 4 Bone for tenderness swelling amp pathological fracturepathological fracture

B) Local examinationB) Local examination

1- inspection1- inspection

BreastBreast compared to healthy side compared to healthy side

Nipple amp areola Nipple amp areola may showmay show

the skinthe skin

1) Skin dimpling Tethering amp Puckering1) Skin dimpling Tethering amp Puckering

2) ulceration amp fungation 2) ulceration amp fungation

3) Peau drsquoorange (Pitted edema) 3) Peau drsquoorange (Pitted edema)

4) Cancerous satellite nodules (late sign) 4) Cancerous satellite nodules (late sign)

5) Cancer en cuirasse5) Cancer en cuirasse

The massThe mass the axillathe axilla The armThe arm

2- palpation2- palpation palpate breasts with both the flat of your palpate breasts with both the flat of your

hand and fingers hand and fingers with flat fingers compress breast tissue with flat fingers compress breast tissue follow systematically in a circular follow systematically in a circular

pattern around the nipple or along the pattern around the nipple or along the radial lines (simulate a clock) or vertical radial lines (simulate a clock) or vertical segments and feel the entire breast segments and feel the entire breast including the tail near the axillaincluding the tail near the axilla

Examine criteria of the mass site size shape consistency

Examine axillary lymph nodes

American Joint Committee on Cancer TNM Staging System for Breast American Joint Committee on Cancer TNM Staging System for Breast Cancer Cancer

Primary Tumor (T)Primary Tumor (T) TX Primary tumor cannot be assessedTX Primary tumor cannot be assessed T0 No evidence of primary tumorT0 No evidence of primary tumor Tis Carcinoma Tis Carcinoma in situin situ

Note Pagets disease associated with a tumor is classified according Note Pagets disease associated with a tumor is classified according to the size of the tumor to the size of the tumor

T1 Tumor 2 cm or less in greatest dimensionT1 Tumor 2 cm or less in greatest dimension

T1mic Microinvasion 01 cm or less in greatest dimensionT1mic Microinvasion 01 cm or less in greatest dimension

T1a Tumor more than 01 cm but not more than 05 cm in greatest T1a Tumor more than 01 cm but not more than 05 cm in greatest dimension dimension

T1b Tumor more than 05 cm but not more than 1 cm in greatest T1b Tumor more than 05 cm but not more than 1 cm in greatest dimension dimension

T1c Tumor more than 1 cm but not more than 2 cm in greatest T1c Tumor more than 1 cm but not more than 2 cm in greatest dimensiondimension

T2 Tumor more than 2 cm but not more than 5 cm in greatest T2 Tumor more than 2 cm but not more than 5 cm in greatest dimensiondimension

T3 Tumor more than 5 cm in greatest dimensionT3 Tumor more than 5 cm in greatest dimension T4a Extension to chest wall not including pectoralis muscleT4a Extension to chest wall not including pectoralis muscle

T4b Edema (including peau dorange) or ulceration of the skin of the T4b Edema (including peau dorange) or ulceration of the skin of the breast or satellite skin nodules confined to the same breast breast or satellite skin nodules confined to the same breast

T4c Both T4a and T4bT4c Both T4a and T4b

T4d Inflammatory carcinomaT4d Inflammatory carcinoma

Regional Lymph Nodes (N) Regional Lymph Nodes (N) NX Regional lymph nodes cannot be assessed (eg NX Regional lymph nodes cannot be assessed (eg

previously removed) previously removed) N0 No regional lymph node metastasisN0 No regional lymph node metastasis N1 Metastasis to movable ipsilateral axillary lymph N1 Metastasis to movable ipsilateral axillary lymph

node(s)node(s) N2 N2

N2a Metastases in ipsilateral axillary lymph nodes N2a Metastases in ipsilateral axillary lymph nodes fixed to one another (matted) or to other structures fixed to one another (matted) or to other structures

N2b Metastasis only in N2b Metastasis only in clinically apparentclinically apparent ipsilateral ipsilateral internal mammary nodes and in theinternal mammary nodes and in the absence absence of of clinically evident axillary lymph node metastasis clinically evident axillary lymph node metastasis

N3N3

N3a Metastasis in ipsilateral infraclavicular lymph N3a Metastasis in ipsilateral infraclavicular lymph node(s)node(s)

N3b Metastasis in ipsilateral internal mammary N3b Metastasis in ipsilateral internal mammary lymph node(s) and axillary lymph node(s) lymph node(s) and axillary lymph node(s)

N3c Metastasis in ipsilateral supraclavicular lymph N3c Metastasis in ipsilateral supraclavicular lymph node(s)node(s)

M ( METASTASIS)M ( METASTASIS)

MX metastasis can no be assessedMX metastasis can no be assessed

M0 no metastasisM0 no metastasis

M1 metastasisM1 metastasis

American Cancer SocietyAmerican Cancer SocietyScreening RecommendationsScreening Recommendations

Annual mammogramsAnnual mammograms starting at starting at age 40age 40

Clinical breast examsClinical breast examsndash every year starting at age 40every year starting at age 40ndash every 3 years for women age every 3 years for women age 20-3920-39

Self-breast examsSelf-breast exams monthly starting monthly starting at age 20at age 20

Breast Self-Exam ndash Step Breast Self-Exam ndash Step 11 Begin by looking at your breasts in the mirror Begin by looking at your breasts in the mirror

with your shoulders straight and yourwith your shoulders straight and your

arms on your hipsarms on your hips Heres what you should look forHeres what you should look for

Breasts that are their usual size shape and colorBreasts that are their usual size shape and color

--Breasts that are evenly shaped without visible --Breasts that are evenly shaped without visible distortion or swellingdistortion or swelling

If you see any of the following changes bring If you see any of the following changes bring them to your doctors attentionthem to your doctors attention

--Dimpling puckering or bulging of the skin--Dimpling puckering or bulging of the skin

--A nipple that has changed position or become --A nipple that has changed position or become inverted (pushed inward instead ofinverted (pushed inward instead of

sticking out)sticking out) --Redness soreness rash or swelling--Redness soreness rash or swelling

Breast Self-Exam ndash Step Breast Self-Exam ndash Step 22

Raise your arms and look for the Raise your arms and look for the

samesame

changeschanges

Breast Self-Exam ndash Step Breast Self-Exam ndash Step 33 Feel your breasts while lying down using Feel your breasts while lying down using

your right hand to feel your left breast and your right hand to feel your left breast and then your left hand to feel your right breast then your left hand to feel your right breast Use a firm smooth touch with the first few Use a firm smooth touch with the first few fingers of your hand keeping the fingersfingers of your hand keeping the fingers

flat and togetherflat and together

Cover the entire breast from top to Cover the entire breast from top to bottom side to sidemdashfrom your bottom side to sidemdashfrom your collarbone to the top of your abdomen collarbone to the top of your abdomen and from your armpit to your cleavageand from your armpit to your cleavage

Breast Self-Exam ndash Step Breast Self-Exam ndash Step 44

Finally feel your breasts while you are Finally feel your breasts while you are standing or sitting Many women find standing or sitting Many women find that the easiest way to feel their breasts that the easiest way to feel their breasts is when their skin is wet and slippery is when their skin is wet and slippery so they like to do this step in the so they like to do this step in the shower Cover your entire breast using shower Cover your entire breast using the same hand movements described in the same hand movements described in Step 3Step 3

InvestigationsInvestigations

Mammography (conrsquot)Mammography (conrsquot) 1048698 1048698 Standard mammography Standard mammography depends on depends on

density of the tissue and its ability to stop density of the tissue and its ability to stop xrayxray

beam from exposing film placed on the other beam from exposing film placed on the other side of the breastside of the breast

Digital mammography Digital mammography works on the same works on the same principle but there is also some ability to principle but there is also some ability to manipulate the image by computer Main manipulate the image by computer Main advantage is storage of the filmsadvantage is storage of the films

UltrasoundUltrasound

Since solid tissue andSince solid tissue and collections of fluid look thecollections of fluid look the same on mammographysame on mammography ultrasound is very useful in ultrasound is very useful in telling whether a mass istelling whether a mass is solid or fluid and if solid ifsolid or fluid and if solid if characteristics arecharacteristics are suspicioussuspicious CystCyst

MRIMRI MRI relies on completely different type of MRI relies on completely different type of

wavewave

energy a strong magnet that affects the energy a strong magnet that affects the charge incharge in

the nuclei As magnetic force is applied and the nuclei As magnetic force is applied and thenthen

released different types of tissue send back released different types of tissue send back different types of radio wavesdifferent types of radio waves

MRI can be extremely useful in very denseMRI can be extremely useful in very dense

breasts hereditary casesbreasts hereditary cases

Fine needle aspiration of a palpable mass

1048698 Fine needle aspiration takes individual cells out ofmass Can be done for palpable or non-palpablemasses Does not show architecture especially wallof duct so best used to confirm strong suspicions

Fine Needle Aspiration

C0 No epithelial cellsC1 InadequateC2 BenignC3 AtypiaC4 SuspiciousC5 Malignant

1048698 Core biopsy can also bedone on palpable and non palpableabnormalities and on microcalcifications

Core Biopsy

B1 Normal tissue unsatisfactoryB2 BenignB3 Lesion uncertain malignant potentialB4 Suspicion of malignancyB5a In situ malignancyB5b Invasive malignancy

Investigations for Investigations for metastasismetastasis

1- abdominal ultrasound1- abdominal ultrasound

2- chest x ray or CT2- chest x ray or CT

3- bone survey or bone scan3- bone survey or bone scan

Established prognostic Established prognostic factorsfactors

bull Nodal status Nodal status bull Tumor size Tumor size bull Lymph node Lymph node bull Grade Grade bull ERPR StatusERPR Statusbull Age Age bull Lymphatic invasionLymphatic invasionbull Histological tumor typeHistological tumor type bull Perinodular infiltrationPerinodular infiltration

TREATMENT OPTIONS FOR PRIMARY OPERABLE BREAST CANCER Objective Options

Local control Lumpectomy Lumpectomy with breast irradiation Mastectomy

Regional control Axillary lymph node dissection Regional irradiation

Control of occult Chemotherapymicrometastatic disease Hormone therapy

Improved function and cosmesis Breast-conserving therapy Reconstruction (immediate or delayed)

Localized breast cancer Surgery is mainstay Halsted 1882 radical mastectomy

John Hopkins

Metastatic breast cancer Systemic treatment

Radical mastectomy A Entire breast and a

chest wall muscle is removed

LNs in the level 1 (B) and level 2 (C ) and even sometimes more distant lymph node groups (D E and F) were also removed

Modified radical mastectomy (MRM)

A Entire breast is removed

Classically some lymph nodes in the level 1 (B) and level 2 (C ) were removed called an axillary lymph node dissection

MRM = simple mastectomy + ALND

Breast conserving surgery

Also called lumpectomy with safety margin with axillary clearance or sentinel lymph node biopsy

RT should be followed

Adjuvant systemic treatment

Hypothesis Eradicate micrometastasis From effective treatment for overt

(macro) metastasis

Chemotherapy Hormone therapy

Adjuvant chemotherapy

CMF first generation 1970s Cyclophosphamide Methotrexate 5-FU

Benefit in Distant recurrence Survival

Adjuvant chemotherapy

CAF or CEF 2nd generation 1980s Cyclophophamide Adramycin(or Epirubicin) 5-FU

More toxic than CMF CAF better than CMF in high-risk group

Axilla LN+ LN- but tumor large or other risk factor

Adjuvant chemotherapy

Incorporate Taxane TAC 3rd generation mid-1990s

Taxotere Adriamycin Cyclophosphamide

More toxic than CAF Better than CAF in high-risk group

Need more time to observe

Adjuvant Herceptin(HER-2 (Human Epidermal growth factor Receptor 2) also

known as proto-oncogene Neu Over expression of this gene is correlated with higher aggressiveness in breast cancer

HER2 is a cell membrane surface-bound receptor tyrosine kinase and is normally involved in the signal transduction pathways leading to cell growth and differentiation)

Effective in Her2+ pts ICH3+ FISH+

Herceptin + adjuvant chemotherapy Optimal role to be defined

Concurrent or sequential Maintenance Duration

Etiology Etiology (predisposing factors)(predisposing factors)

1-Genetic1-Genetic

A-Young age lt 30 yrA-Young age lt 30 yr

b- Mostly Bilateralb- Mostly Bilateral

c- Multiple relatives with cancer breast (gt3) c- Multiple relatives with cancer breast (gt3)

-Hereditary breast cancer 5ndash10-Hereditary breast cancer 5ndash10 BRCA-1 BRCA-1 Long arm of chromosome 17qLong arm of chromosome 17q BRCA-2 BRCA-2 Long arm of chromosome 13qLong arm of chromosome 13q Li-Fraumeni syndrome P53 Li-Fraumeni syndrome P53 Short arm chromosome Short arm chromosome

17p17p

2- Endocrinal (Hormonal)2- Endocrinal (Hormonal)

- Not married null Para elderly primigravida - Not married null Para elderly primigravida (gt 35 yr) and non-lactating female (gt 35 yr) and non-lactating female

- Early menarche or late menopause due to - Early menarche or late menopause due to prolonged exposure to estrogenprolonged exposure to estrogen

3- Exposure to radiation3- Exposure to radiation

- Nuclear war - Nuclear war

- Medical purposes (diagnostic or therapeutic - Medical purposes (diagnostic or therapeutic being greater for exposures in childhood and being greater for exposures in childhood and adolescence than after age of 40 years)adolescence than after age of 40 years)

4-drugs estrogen contraceptive pills more 4-drugs estrogen contraceptive pills more than 10 years (uncertain)than 10 years (uncertain)

pathologypathology World Health Organization Classification of World Health Organization Classification of

Carcinoma of the Breast Carcinoma of the Breast Noninvasive carcinomaNoninvasive carcinoma

-Ductal carcinoma -Ductal carcinoma in situin situ -Lobular carcinoma -Lobular carcinoma in situin situ Invasive carcinomaInvasive carcinoma

-Invasive ductal carcinoma -- 80-Invasive ductal carcinoma -- 80

-Invasive lobular carcinoma ndash 10-Invasive lobular carcinoma ndash 10

-Mucinous carcinoma -- 2-Mucinous carcinoma -- 2

-Medullary carcinoma ndash 5-Medullary carcinoma ndash 5

-Papillary carcinoma -- 1-Papillary carcinoma -- 1

-Tubular carcinoma ndash 1-Tubular carcinoma ndash 1

-Adenoid cystic carcinoma-Adenoid cystic carcinoma

-Secretory (juvenile) carcinoma-Secretory (juvenile) carcinoma

-Apocrine carcinoma-Apocrine carcinoma

-Carcinoma with metaplasia (metaplastic carcinoma)-Carcinoma with metaplasia (metaplastic carcinoma)

-Inflammatory carcinoma-Inflammatory carcinoma

-Other sarcoma lymphoma and melanoma-Other sarcoma lymphoma and melanoma Pagets disease of the nipplePagets disease of the nipple

SpreadSpreadDirect spread-Direct spread-

11 Intrinsic Intrinsic to surrounding breast tissue to surrounding breast tissue

2 2 ExtrinsicExtrinsic

To the skin causing ulceration amp To the skin causing ulceration amp fungation fungation

To deep structures Pectoral fascia To deep structures Pectoral fascia pectoral muscles amp chest wallpectoral muscles amp chest wall

Lymphatic spread-Lymphatic spread-

Haematogenous spread- Haematogenous spread-

Transcoelomic spread-Transcoelomic spread-

Clinical pictureClinical picture Symptoms Symptoms

A- AsymptomaticA- Asymptomatic- - discovered discovered accidentally during screening programs accidentally during screening programs

B- SymptomaticB- Symptomatic- -

1 Mass 1 Mass ((commonest presentationcommonest presentation) )

2 Pain2 Pain ( (Very Rare 10Very Rare 10))

3 Nipple discharge 3 Nipple discharge - Bloody discharge - Bloody discharge in duct carcinoma in duct carcinoma

4 Skin amp nipple manifestations4 Skin amp nipple manifestations

5 Manifestations of metastasis- 5 Manifestations of metastasis-

Signs Signs

A) General examinationsA) General examinations

1 Chest signs of pleural effusion or 1 Chest signs of pleural effusion or mediastinal LNmediastinal LN

2 Abdominal examination2 Abdominal examination

- Hepatomegaly - Ascites- Hepatomegaly - Ascites

3 PR or PV nodules in the 3 PR or PV nodules in the Douglasrsquo pouch or Krukenbergrsquos Douglasrsquo pouch or Krukenbergrsquos tumortumor

4 Bone for tenderness swelling amp 4 Bone for tenderness swelling amp pathological fracturepathological fracture

B) Local examinationB) Local examination

1- inspection1- inspection

BreastBreast compared to healthy side compared to healthy side

Nipple amp areola Nipple amp areola may showmay show

the skinthe skin

1) Skin dimpling Tethering amp Puckering1) Skin dimpling Tethering amp Puckering

2) ulceration amp fungation 2) ulceration amp fungation

3) Peau drsquoorange (Pitted edema) 3) Peau drsquoorange (Pitted edema)

4) Cancerous satellite nodules (late sign) 4) Cancerous satellite nodules (late sign)

5) Cancer en cuirasse5) Cancer en cuirasse

The massThe mass the axillathe axilla The armThe arm

2- palpation2- palpation palpate breasts with both the flat of your palpate breasts with both the flat of your

hand and fingers hand and fingers with flat fingers compress breast tissue with flat fingers compress breast tissue follow systematically in a circular follow systematically in a circular

pattern around the nipple or along the pattern around the nipple or along the radial lines (simulate a clock) or vertical radial lines (simulate a clock) or vertical segments and feel the entire breast segments and feel the entire breast including the tail near the axillaincluding the tail near the axilla

Examine criteria of the mass site size shape consistency

Examine axillary lymph nodes

American Joint Committee on Cancer TNM Staging System for Breast American Joint Committee on Cancer TNM Staging System for Breast Cancer Cancer

Primary Tumor (T)Primary Tumor (T) TX Primary tumor cannot be assessedTX Primary tumor cannot be assessed T0 No evidence of primary tumorT0 No evidence of primary tumor Tis Carcinoma Tis Carcinoma in situin situ

Note Pagets disease associated with a tumor is classified according Note Pagets disease associated with a tumor is classified according to the size of the tumor to the size of the tumor

T1 Tumor 2 cm or less in greatest dimensionT1 Tumor 2 cm or less in greatest dimension

T1mic Microinvasion 01 cm or less in greatest dimensionT1mic Microinvasion 01 cm or less in greatest dimension

T1a Tumor more than 01 cm but not more than 05 cm in greatest T1a Tumor more than 01 cm but not more than 05 cm in greatest dimension dimension

T1b Tumor more than 05 cm but not more than 1 cm in greatest T1b Tumor more than 05 cm but not more than 1 cm in greatest dimension dimension

T1c Tumor more than 1 cm but not more than 2 cm in greatest T1c Tumor more than 1 cm but not more than 2 cm in greatest dimensiondimension

T2 Tumor more than 2 cm but not more than 5 cm in greatest T2 Tumor more than 2 cm but not more than 5 cm in greatest dimensiondimension

T3 Tumor more than 5 cm in greatest dimensionT3 Tumor more than 5 cm in greatest dimension T4a Extension to chest wall not including pectoralis muscleT4a Extension to chest wall not including pectoralis muscle

T4b Edema (including peau dorange) or ulceration of the skin of the T4b Edema (including peau dorange) or ulceration of the skin of the breast or satellite skin nodules confined to the same breast breast or satellite skin nodules confined to the same breast

T4c Both T4a and T4bT4c Both T4a and T4b

T4d Inflammatory carcinomaT4d Inflammatory carcinoma

Regional Lymph Nodes (N) Regional Lymph Nodes (N) NX Regional lymph nodes cannot be assessed (eg NX Regional lymph nodes cannot be assessed (eg

previously removed) previously removed) N0 No regional lymph node metastasisN0 No regional lymph node metastasis N1 Metastasis to movable ipsilateral axillary lymph N1 Metastasis to movable ipsilateral axillary lymph

node(s)node(s) N2 N2

N2a Metastases in ipsilateral axillary lymph nodes N2a Metastases in ipsilateral axillary lymph nodes fixed to one another (matted) or to other structures fixed to one another (matted) or to other structures

N2b Metastasis only in N2b Metastasis only in clinically apparentclinically apparent ipsilateral ipsilateral internal mammary nodes and in theinternal mammary nodes and in the absence absence of of clinically evident axillary lymph node metastasis clinically evident axillary lymph node metastasis

N3N3

N3a Metastasis in ipsilateral infraclavicular lymph N3a Metastasis in ipsilateral infraclavicular lymph node(s)node(s)

N3b Metastasis in ipsilateral internal mammary N3b Metastasis in ipsilateral internal mammary lymph node(s) and axillary lymph node(s) lymph node(s) and axillary lymph node(s)

N3c Metastasis in ipsilateral supraclavicular lymph N3c Metastasis in ipsilateral supraclavicular lymph node(s)node(s)

M ( METASTASIS)M ( METASTASIS)

MX metastasis can no be assessedMX metastasis can no be assessed

M0 no metastasisM0 no metastasis

M1 metastasisM1 metastasis

American Cancer SocietyAmerican Cancer SocietyScreening RecommendationsScreening Recommendations

Annual mammogramsAnnual mammograms starting at starting at age 40age 40

Clinical breast examsClinical breast examsndash every year starting at age 40every year starting at age 40ndash every 3 years for women age every 3 years for women age 20-3920-39

Self-breast examsSelf-breast exams monthly starting monthly starting at age 20at age 20

Breast Self-Exam ndash Step Breast Self-Exam ndash Step 11 Begin by looking at your breasts in the mirror Begin by looking at your breasts in the mirror

with your shoulders straight and yourwith your shoulders straight and your

arms on your hipsarms on your hips Heres what you should look forHeres what you should look for

Breasts that are their usual size shape and colorBreasts that are their usual size shape and color

--Breasts that are evenly shaped without visible --Breasts that are evenly shaped without visible distortion or swellingdistortion or swelling

If you see any of the following changes bring If you see any of the following changes bring them to your doctors attentionthem to your doctors attention

--Dimpling puckering or bulging of the skin--Dimpling puckering or bulging of the skin

--A nipple that has changed position or become --A nipple that has changed position or become inverted (pushed inward instead ofinverted (pushed inward instead of

sticking out)sticking out) --Redness soreness rash or swelling--Redness soreness rash or swelling

Breast Self-Exam ndash Step Breast Self-Exam ndash Step 22

Raise your arms and look for the Raise your arms and look for the

samesame

changeschanges

Breast Self-Exam ndash Step Breast Self-Exam ndash Step 33 Feel your breasts while lying down using Feel your breasts while lying down using

your right hand to feel your left breast and your right hand to feel your left breast and then your left hand to feel your right breast then your left hand to feel your right breast Use a firm smooth touch with the first few Use a firm smooth touch with the first few fingers of your hand keeping the fingersfingers of your hand keeping the fingers

flat and togetherflat and together

Cover the entire breast from top to Cover the entire breast from top to bottom side to sidemdashfrom your bottom side to sidemdashfrom your collarbone to the top of your abdomen collarbone to the top of your abdomen and from your armpit to your cleavageand from your armpit to your cleavage

Breast Self-Exam ndash Step Breast Self-Exam ndash Step 44

Finally feel your breasts while you are Finally feel your breasts while you are standing or sitting Many women find standing or sitting Many women find that the easiest way to feel their breasts that the easiest way to feel their breasts is when their skin is wet and slippery is when their skin is wet and slippery so they like to do this step in the so they like to do this step in the shower Cover your entire breast using shower Cover your entire breast using the same hand movements described in the same hand movements described in Step 3Step 3

InvestigationsInvestigations

Mammography (conrsquot)Mammography (conrsquot) 1048698 1048698 Standard mammography Standard mammography depends on depends on

density of the tissue and its ability to stop density of the tissue and its ability to stop xrayxray

beam from exposing film placed on the other beam from exposing film placed on the other side of the breastside of the breast

Digital mammography Digital mammography works on the same works on the same principle but there is also some ability to principle but there is also some ability to manipulate the image by computer Main manipulate the image by computer Main advantage is storage of the filmsadvantage is storage of the films

UltrasoundUltrasound

Since solid tissue andSince solid tissue and collections of fluid look thecollections of fluid look the same on mammographysame on mammography ultrasound is very useful in ultrasound is very useful in telling whether a mass istelling whether a mass is solid or fluid and if solid ifsolid or fluid and if solid if characteristics arecharacteristics are suspicioussuspicious CystCyst

MRIMRI MRI relies on completely different type of MRI relies on completely different type of

wavewave

energy a strong magnet that affects the energy a strong magnet that affects the charge incharge in

the nuclei As magnetic force is applied and the nuclei As magnetic force is applied and thenthen

released different types of tissue send back released different types of tissue send back different types of radio wavesdifferent types of radio waves

MRI can be extremely useful in very denseMRI can be extremely useful in very dense

breasts hereditary casesbreasts hereditary cases

Fine needle aspiration of a palpable mass

1048698 Fine needle aspiration takes individual cells out ofmass Can be done for palpable or non-palpablemasses Does not show architecture especially wallof duct so best used to confirm strong suspicions

Fine Needle Aspiration

C0 No epithelial cellsC1 InadequateC2 BenignC3 AtypiaC4 SuspiciousC5 Malignant

1048698 Core biopsy can also bedone on palpable and non palpableabnormalities and on microcalcifications

Core Biopsy

B1 Normal tissue unsatisfactoryB2 BenignB3 Lesion uncertain malignant potentialB4 Suspicion of malignancyB5a In situ malignancyB5b Invasive malignancy

Investigations for Investigations for metastasismetastasis

1- abdominal ultrasound1- abdominal ultrasound

2- chest x ray or CT2- chest x ray or CT

3- bone survey or bone scan3- bone survey or bone scan

Established prognostic Established prognostic factorsfactors

bull Nodal status Nodal status bull Tumor size Tumor size bull Lymph node Lymph node bull Grade Grade bull ERPR StatusERPR Statusbull Age Age bull Lymphatic invasionLymphatic invasionbull Histological tumor typeHistological tumor type bull Perinodular infiltrationPerinodular infiltration

TREATMENT OPTIONS FOR PRIMARY OPERABLE BREAST CANCER Objective Options

Local control Lumpectomy Lumpectomy with breast irradiation Mastectomy

Regional control Axillary lymph node dissection Regional irradiation

Control of occult Chemotherapymicrometastatic disease Hormone therapy

Improved function and cosmesis Breast-conserving therapy Reconstruction (immediate or delayed)

Localized breast cancer Surgery is mainstay Halsted 1882 radical mastectomy

John Hopkins

Metastatic breast cancer Systemic treatment

Radical mastectomy A Entire breast and a

chest wall muscle is removed

LNs in the level 1 (B) and level 2 (C ) and even sometimes more distant lymph node groups (D E and F) were also removed

Modified radical mastectomy (MRM)

A Entire breast is removed

Classically some lymph nodes in the level 1 (B) and level 2 (C ) were removed called an axillary lymph node dissection

MRM = simple mastectomy + ALND

Breast conserving surgery

Also called lumpectomy with safety margin with axillary clearance or sentinel lymph node biopsy

RT should be followed

Adjuvant systemic treatment

Hypothesis Eradicate micrometastasis From effective treatment for overt

(macro) metastasis

Chemotherapy Hormone therapy

Adjuvant chemotherapy

CMF first generation 1970s Cyclophosphamide Methotrexate 5-FU

Benefit in Distant recurrence Survival

Adjuvant chemotherapy

CAF or CEF 2nd generation 1980s Cyclophophamide Adramycin(or Epirubicin) 5-FU

More toxic than CMF CAF better than CMF in high-risk group

Axilla LN+ LN- but tumor large or other risk factor

Adjuvant chemotherapy

Incorporate Taxane TAC 3rd generation mid-1990s

Taxotere Adriamycin Cyclophosphamide

More toxic than CAF Better than CAF in high-risk group

Need more time to observe

Adjuvant Herceptin(HER-2 (Human Epidermal growth factor Receptor 2) also

known as proto-oncogene Neu Over expression of this gene is correlated with higher aggressiveness in breast cancer

HER2 is a cell membrane surface-bound receptor tyrosine kinase and is normally involved in the signal transduction pathways leading to cell growth and differentiation)

Effective in Her2+ pts ICH3+ FISH+

Herceptin + adjuvant chemotherapy Optimal role to be defined

Concurrent or sequential Maintenance Duration

2- Endocrinal (Hormonal)2- Endocrinal (Hormonal)

- Not married null Para elderly primigravida - Not married null Para elderly primigravida (gt 35 yr) and non-lactating female (gt 35 yr) and non-lactating female

- Early menarche or late menopause due to - Early menarche or late menopause due to prolonged exposure to estrogenprolonged exposure to estrogen

3- Exposure to radiation3- Exposure to radiation

- Nuclear war - Nuclear war

- Medical purposes (diagnostic or therapeutic - Medical purposes (diagnostic or therapeutic being greater for exposures in childhood and being greater for exposures in childhood and adolescence than after age of 40 years)adolescence than after age of 40 years)

4-drugs estrogen contraceptive pills more 4-drugs estrogen contraceptive pills more than 10 years (uncertain)than 10 years (uncertain)

pathologypathology World Health Organization Classification of World Health Organization Classification of

Carcinoma of the Breast Carcinoma of the Breast Noninvasive carcinomaNoninvasive carcinoma

-Ductal carcinoma -Ductal carcinoma in situin situ -Lobular carcinoma -Lobular carcinoma in situin situ Invasive carcinomaInvasive carcinoma

-Invasive ductal carcinoma -- 80-Invasive ductal carcinoma -- 80

-Invasive lobular carcinoma ndash 10-Invasive lobular carcinoma ndash 10

-Mucinous carcinoma -- 2-Mucinous carcinoma -- 2

-Medullary carcinoma ndash 5-Medullary carcinoma ndash 5

-Papillary carcinoma -- 1-Papillary carcinoma -- 1

-Tubular carcinoma ndash 1-Tubular carcinoma ndash 1

-Adenoid cystic carcinoma-Adenoid cystic carcinoma

-Secretory (juvenile) carcinoma-Secretory (juvenile) carcinoma

-Apocrine carcinoma-Apocrine carcinoma

-Carcinoma with metaplasia (metaplastic carcinoma)-Carcinoma with metaplasia (metaplastic carcinoma)

-Inflammatory carcinoma-Inflammatory carcinoma

-Other sarcoma lymphoma and melanoma-Other sarcoma lymphoma and melanoma Pagets disease of the nipplePagets disease of the nipple

SpreadSpreadDirect spread-Direct spread-

11 Intrinsic Intrinsic to surrounding breast tissue to surrounding breast tissue

2 2 ExtrinsicExtrinsic

To the skin causing ulceration amp To the skin causing ulceration amp fungation fungation

To deep structures Pectoral fascia To deep structures Pectoral fascia pectoral muscles amp chest wallpectoral muscles amp chest wall

Lymphatic spread-Lymphatic spread-

Haematogenous spread- Haematogenous spread-

Transcoelomic spread-Transcoelomic spread-

Clinical pictureClinical picture Symptoms Symptoms

A- AsymptomaticA- Asymptomatic- - discovered discovered accidentally during screening programs accidentally during screening programs

B- SymptomaticB- Symptomatic- -

1 Mass 1 Mass ((commonest presentationcommonest presentation) )

2 Pain2 Pain ( (Very Rare 10Very Rare 10))

3 Nipple discharge 3 Nipple discharge - Bloody discharge - Bloody discharge in duct carcinoma in duct carcinoma

4 Skin amp nipple manifestations4 Skin amp nipple manifestations

5 Manifestations of metastasis- 5 Manifestations of metastasis-

Signs Signs

A) General examinationsA) General examinations

1 Chest signs of pleural effusion or 1 Chest signs of pleural effusion or mediastinal LNmediastinal LN

2 Abdominal examination2 Abdominal examination

- Hepatomegaly - Ascites- Hepatomegaly - Ascites

3 PR or PV nodules in the 3 PR or PV nodules in the Douglasrsquo pouch or Krukenbergrsquos Douglasrsquo pouch or Krukenbergrsquos tumortumor

4 Bone for tenderness swelling amp 4 Bone for tenderness swelling amp pathological fracturepathological fracture

B) Local examinationB) Local examination

1- inspection1- inspection

BreastBreast compared to healthy side compared to healthy side

Nipple amp areola Nipple amp areola may showmay show

the skinthe skin

1) Skin dimpling Tethering amp Puckering1) Skin dimpling Tethering amp Puckering

2) ulceration amp fungation 2) ulceration amp fungation

3) Peau drsquoorange (Pitted edema) 3) Peau drsquoorange (Pitted edema)

4) Cancerous satellite nodules (late sign) 4) Cancerous satellite nodules (late sign)

5) Cancer en cuirasse5) Cancer en cuirasse

The massThe mass the axillathe axilla The armThe arm

2- palpation2- palpation palpate breasts with both the flat of your palpate breasts with both the flat of your

hand and fingers hand and fingers with flat fingers compress breast tissue with flat fingers compress breast tissue follow systematically in a circular follow systematically in a circular

pattern around the nipple or along the pattern around the nipple or along the radial lines (simulate a clock) or vertical radial lines (simulate a clock) or vertical segments and feel the entire breast segments and feel the entire breast including the tail near the axillaincluding the tail near the axilla

Examine criteria of the mass site size shape consistency

Examine axillary lymph nodes

American Joint Committee on Cancer TNM Staging System for Breast American Joint Committee on Cancer TNM Staging System for Breast Cancer Cancer

Primary Tumor (T)Primary Tumor (T) TX Primary tumor cannot be assessedTX Primary tumor cannot be assessed T0 No evidence of primary tumorT0 No evidence of primary tumor Tis Carcinoma Tis Carcinoma in situin situ

Note Pagets disease associated with a tumor is classified according Note Pagets disease associated with a tumor is classified according to the size of the tumor to the size of the tumor

T1 Tumor 2 cm or less in greatest dimensionT1 Tumor 2 cm or less in greatest dimension

T1mic Microinvasion 01 cm or less in greatest dimensionT1mic Microinvasion 01 cm or less in greatest dimension

T1a Tumor more than 01 cm but not more than 05 cm in greatest T1a Tumor more than 01 cm but not more than 05 cm in greatest dimension dimension

T1b Tumor more than 05 cm but not more than 1 cm in greatest T1b Tumor more than 05 cm but not more than 1 cm in greatest dimension dimension

T1c Tumor more than 1 cm but not more than 2 cm in greatest T1c Tumor more than 1 cm but not more than 2 cm in greatest dimensiondimension

T2 Tumor more than 2 cm but not more than 5 cm in greatest T2 Tumor more than 2 cm but not more than 5 cm in greatest dimensiondimension

T3 Tumor more than 5 cm in greatest dimensionT3 Tumor more than 5 cm in greatest dimension T4a Extension to chest wall not including pectoralis muscleT4a Extension to chest wall not including pectoralis muscle

T4b Edema (including peau dorange) or ulceration of the skin of the T4b Edema (including peau dorange) or ulceration of the skin of the breast or satellite skin nodules confined to the same breast breast or satellite skin nodules confined to the same breast

T4c Both T4a and T4bT4c Both T4a and T4b

T4d Inflammatory carcinomaT4d Inflammatory carcinoma

Regional Lymph Nodes (N) Regional Lymph Nodes (N) NX Regional lymph nodes cannot be assessed (eg NX Regional lymph nodes cannot be assessed (eg

previously removed) previously removed) N0 No regional lymph node metastasisN0 No regional lymph node metastasis N1 Metastasis to movable ipsilateral axillary lymph N1 Metastasis to movable ipsilateral axillary lymph

node(s)node(s) N2 N2

N2a Metastases in ipsilateral axillary lymph nodes N2a Metastases in ipsilateral axillary lymph nodes fixed to one another (matted) or to other structures fixed to one another (matted) or to other structures

N2b Metastasis only in N2b Metastasis only in clinically apparentclinically apparent ipsilateral ipsilateral internal mammary nodes and in theinternal mammary nodes and in the absence absence of of clinically evident axillary lymph node metastasis clinically evident axillary lymph node metastasis

N3N3

N3a Metastasis in ipsilateral infraclavicular lymph N3a Metastasis in ipsilateral infraclavicular lymph node(s)node(s)

N3b Metastasis in ipsilateral internal mammary N3b Metastasis in ipsilateral internal mammary lymph node(s) and axillary lymph node(s) lymph node(s) and axillary lymph node(s)

N3c Metastasis in ipsilateral supraclavicular lymph N3c Metastasis in ipsilateral supraclavicular lymph node(s)node(s)

M ( METASTASIS)M ( METASTASIS)

MX metastasis can no be assessedMX metastasis can no be assessed

M0 no metastasisM0 no metastasis

M1 metastasisM1 metastasis

American Cancer SocietyAmerican Cancer SocietyScreening RecommendationsScreening Recommendations

Annual mammogramsAnnual mammograms starting at starting at age 40age 40

Clinical breast examsClinical breast examsndash every year starting at age 40every year starting at age 40ndash every 3 years for women age every 3 years for women age 20-3920-39

Self-breast examsSelf-breast exams monthly starting monthly starting at age 20at age 20

Breast Self-Exam ndash Step Breast Self-Exam ndash Step 11 Begin by looking at your breasts in the mirror Begin by looking at your breasts in the mirror

with your shoulders straight and yourwith your shoulders straight and your

arms on your hipsarms on your hips Heres what you should look forHeres what you should look for

Breasts that are their usual size shape and colorBreasts that are their usual size shape and color

--Breasts that are evenly shaped without visible --Breasts that are evenly shaped without visible distortion or swellingdistortion or swelling

If you see any of the following changes bring If you see any of the following changes bring them to your doctors attentionthem to your doctors attention

--Dimpling puckering or bulging of the skin--Dimpling puckering or bulging of the skin

--A nipple that has changed position or become --A nipple that has changed position or become inverted (pushed inward instead ofinverted (pushed inward instead of

sticking out)sticking out) --Redness soreness rash or swelling--Redness soreness rash or swelling

Breast Self-Exam ndash Step Breast Self-Exam ndash Step 22

Raise your arms and look for the Raise your arms and look for the

samesame

changeschanges

Breast Self-Exam ndash Step Breast Self-Exam ndash Step 33 Feel your breasts while lying down using Feel your breasts while lying down using

your right hand to feel your left breast and your right hand to feel your left breast and then your left hand to feel your right breast then your left hand to feel your right breast Use a firm smooth touch with the first few Use a firm smooth touch with the first few fingers of your hand keeping the fingersfingers of your hand keeping the fingers

flat and togetherflat and together

Cover the entire breast from top to Cover the entire breast from top to bottom side to sidemdashfrom your bottom side to sidemdashfrom your collarbone to the top of your abdomen collarbone to the top of your abdomen and from your armpit to your cleavageand from your armpit to your cleavage

Breast Self-Exam ndash Step Breast Self-Exam ndash Step 44

Finally feel your breasts while you are Finally feel your breasts while you are standing or sitting Many women find standing or sitting Many women find that the easiest way to feel their breasts that the easiest way to feel their breasts is when their skin is wet and slippery is when their skin is wet and slippery so they like to do this step in the so they like to do this step in the shower Cover your entire breast using shower Cover your entire breast using the same hand movements described in the same hand movements described in Step 3Step 3

InvestigationsInvestigations

Mammography (conrsquot)Mammography (conrsquot) 1048698 1048698 Standard mammography Standard mammography depends on depends on

density of the tissue and its ability to stop density of the tissue and its ability to stop xrayxray

beam from exposing film placed on the other beam from exposing film placed on the other side of the breastside of the breast

Digital mammography Digital mammography works on the same works on the same principle but there is also some ability to principle but there is also some ability to manipulate the image by computer Main manipulate the image by computer Main advantage is storage of the filmsadvantage is storage of the films

UltrasoundUltrasound

Since solid tissue andSince solid tissue and collections of fluid look thecollections of fluid look the same on mammographysame on mammography ultrasound is very useful in ultrasound is very useful in telling whether a mass istelling whether a mass is solid or fluid and if solid ifsolid or fluid and if solid if characteristics arecharacteristics are suspicioussuspicious CystCyst

MRIMRI MRI relies on completely different type of MRI relies on completely different type of

wavewave

energy a strong magnet that affects the energy a strong magnet that affects the charge incharge in

the nuclei As magnetic force is applied and the nuclei As magnetic force is applied and thenthen

released different types of tissue send back released different types of tissue send back different types of radio wavesdifferent types of radio waves

MRI can be extremely useful in very denseMRI can be extremely useful in very dense

breasts hereditary casesbreasts hereditary cases

Fine needle aspiration of a palpable mass

1048698 Fine needle aspiration takes individual cells out ofmass Can be done for palpable or non-palpablemasses Does not show architecture especially wallof duct so best used to confirm strong suspicions

Fine Needle Aspiration

C0 No epithelial cellsC1 InadequateC2 BenignC3 AtypiaC4 SuspiciousC5 Malignant

1048698 Core biopsy can also bedone on palpable and non palpableabnormalities and on microcalcifications

Core Biopsy

B1 Normal tissue unsatisfactoryB2 BenignB3 Lesion uncertain malignant potentialB4 Suspicion of malignancyB5a In situ malignancyB5b Invasive malignancy

Investigations for Investigations for metastasismetastasis

1- abdominal ultrasound1- abdominal ultrasound

2- chest x ray or CT2- chest x ray or CT

3- bone survey or bone scan3- bone survey or bone scan

Established prognostic Established prognostic factorsfactors

bull Nodal status Nodal status bull Tumor size Tumor size bull Lymph node Lymph node bull Grade Grade bull ERPR StatusERPR Statusbull Age Age bull Lymphatic invasionLymphatic invasionbull Histological tumor typeHistological tumor type bull Perinodular infiltrationPerinodular infiltration

TREATMENT OPTIONS FOR PRIMARY OPERABLE BREAST CANCER Objective Options

Local control Lumpectomy Lumpectomy with breast irradiation Mastectomy

Regional control Axillary lymph node dissection Regional irradiation

Control of occult Chemotherapymicrometastatic disease Hormone therapy

Improved function and cosmesis Breast-conserving therapy Reconstruction (immediate or delayed)

Localized breast cancer Surgery is mainstay Halsted 1882 radical mastectomy

John Hopkins

Metastatic breast cancer Systemic treatment

Radical mastectomy A Entire breast and a

chest wall muscle is removed

LNs in the level 1 (B) and level 2 (C ) and even sometimes more distant lymph node groups (D E and F) were also removed

Modified radical mastectomy (MRM)

A Entire breast is removed

Classically some lymph nodes in the level 1 (B) and level 2 (C ) were removed called an axillary lymph node dissection

MRM = simple mastectomy + ALND

Breast conserving surgery

Also called lumpectomy with safety margin with axillary clearance or sentinel lymph node biopsy

RT should be followed

Adjuvant systemic treatment

Hypothesis Eradicate micrometastasis From effective treatment for overt

(macro) metastasis

Chemotherapy Hormone therapy

Adjuvant chemotherapy

CMF first generation 1970s Cyclophosphamide Methotrexate 5-FU

Benefit in Distant recurrence Survival

Adjuvant chemotherapy

CAF or CEF 2nd generation 1980s Cyclophophamide Adramycin(or Epirubicin) 5-FU

More toxic than CMF CAF better than CMF in high-risk group

Axilla LN+ LN- but tumor large or other risk factor

Adjuvant chemotherapy

Incorporate Taxane TAC 3rd generation mid-1990s

Taxotere Adriamycin Cyclophosphamide

More toxic than CAF Better than CAF in high-risk group

Need more time to observe

Adjuvant Herceptin(HER-2 (Human Epidermal growth factor Receptor 2) also

known as proto-oncogene Neu Over expression of this gene is correlated with higher aggressiveness in breast cancer

HER2 is a cell membrane surface-bound receptor tyrosine kinase and is normally involved in the signal transduction pathways leading to cell growth and differentiation)

Effective in Her2+ pts ICH3+ FISH+

Herceptin + adjuvant chemotherapy Optimal role to be defined

Concurrent or sequential Maintenance Duration

pathologypathology World Health Organization Classification of World Health Organization Classification of

Carcinoma of the Breast Carcinoma of the Breast Noninvasive carcinomaNoninvasive carcinoma

-Ductal carcinoma -Ductal carcinoma in situin situ -Lobular carcinoma -Lobular carcinoma in situin situ Invasive carcinomaInvasive carcinoma

-Invasive ductal carcinoma -- 80-Invasive ductal carcinoma -- 80

-Invasive lobular carcinoma ndash 10-Invasive lobular carcinoma ndash 10

-Mucinous carcinoma -- 2-Mucinous carcinoma -- 2

-Medullary carcinoma ndash 5-Medullary carcinoma ndash 5

-Papillary carcinoma -- 1-Papillary carcinoma -- 1

-Tubular carcinoma ndash 1-Tubular carcinoma ndash 1

-Adenoid cystic carcinoma-Adenoid cystic carcinoma

-Secretory (juvenile) carcinoma-Secretory (juvenile) carcinoma

-Apocrine carcinoma-Apocrine carcinoma

-Carcinoma with metaplasia (metaplastic carcinoma)-Carcinoma with metaplasia (metaplastic carcinoma)

-Inflammatory carcinoma-Inflammatory carcinoma

-Other sarcoma lymphoma and melanoma-Other sarcoma lymphoma and melanoma Pagets disease of the nipplePagets disease of the nipple

SpreadSpreadDirect spread-Direct spread-

11 Intrinsic Intrinsic to surrounding breast tissue to surrounding breast tissue

2 2 ExtrinsicExtrinsic

To the skin causing ulceration amp To the skin causing ulceration amp fungation fungation

To deep structures Pectoral fascia To deep structures Pectoral fascia pectoral muscles amp chest wallpectoral muscles amp chest wall

Lymphatic spread-Lymphatic spread-

Haematogenous spread- Haematogenous spread-

Transcoelomic spread-Transcoelomic spread-

Clinical pictureClinical picture Symptoms Symptoms

A- AsymptomaticA- Asymptomatic- - discovered discovered accidentally during screening programs accidentally during screening programs

B- SymptomaticB- Symptomatic- -

1 Mass 1 Mass ((commonest presentationcommonest presentation) )

2 Pain2 Pain ( (Very Rare 10Very Rare 10))

3 Nipple discharge 3 Nipple discharge - Bloody discharge - Bloody discharge in duct carcinoma in duct carcinoma

4 Skin amp nipple manifestations4 Skin amp nipple manifestations

5 Manifestations of metastasis- 5 Manifestations of metastasis-

Signs Signs

A) General examinationsA) General examinations

1 Chest signs of pleural effusion or 1 Chest signs of pleural effusion or mediastinal LNmediastinal LN

2 Abdominal examination2 Abdominal examination

- Hepatomegaly - Ascites- Hepatomegaly - Ascites

3 PR or PV nodules in the 3 PR or PV nodules in the Douglasrsquo pouch or Krukenbergrsquos Douglasrsquo pouch or Krukenbergrsquos tumortumor

4 Bone for tenderness swelling amp 4 Bone for tenderness swelling amp pathological fracturepathological fracture

B) Local examinationB) Local examination

1- inspection1- inspection

BreastBreast compared to healthy side compared to healthy side

Nipple amp areola Nipple amp areola may showmay show

the skinthe skin

1) Skin dimpling Tethering amp Puckering1) Skin dimpling Tethering amp Puckering

2) ulceration amp fungation 2) ulceration amp fungation

3) Peau drsquoorange (Pitted edema) 3) Peau drsquoorange (Pitted edema)

4) Cancerous satellite nodules (late sign) 4) Cancerous satellite nodules (late sign)

5) Cancer en cuirasse5) Cancer en cuirasse

The massThe mass the axillathe axilla The armThe arm

2- palpation2- palpation palpate breasts with both the flat of your palpate breasts with both the flat of your

hand and fingers hand and fingers with flat fingers compress breast tissue with flat fingers compress breast tissue follow systematically in a circular follow systematically in a circular

pattern around the nipple or along the pattern around the nipple or along the radial lines (simulate a clock) or vertical radial lines (simulate a clock) or vertical segments and feel the entire breast segments and feel the entire breast including the tail near the axillaincluding the tail near the axilla

Examine criteria of the mass site size shape consistency

Examine axillary lymph nodes

American Joint Committee on Cancer TNM Staging System for Breast American Joint Committee on Cancer TNM Staging System for Breast Cancer Cancer

Primary Tumor (T)Primary Tumor (T) TX Primary tumor cannot be assessedTX Primary tumor cannot be assessed T0 No evidence of primary tumorT0 No evidence of primary tumor Tis Carcinoma Tis Carcinoma in situin situ

Note Pagets disease associated with a tumor is classified according Note Pagets disease associated with a tumor is classified according to the size of the tumor to the size of the tumor

T1 Tumor 2 cm or less in greatest dimensionT1 Tumor 2 cm or less in greatest dimension

T1mic Microinvasion 01 cm or less in greatest dimensionT1mic Microinvasion 01 cm or less in greatest dimension

T1a Tumor more than 01 cm but not more than 05 cm in greatest T1a Tumor more than 01 cm but not more than 05 cm in greatest dimension dimension

T1b Tumor more than 05 cm but not more than 1 cm in greatest T1b Tumor more than 05 cm but not more than 1 cm in greatest dimension dimension

T1c Tumor more than 1 cm but not more than 2 cm in greatest T1c Tumor more than 1 cm but not more than 2 cm in greatest dimensiondimension

T2 Tumor more than 2 cm but not more than 5 cm in greatest T2 Tumor more than 2 cm but not more than 5 cm in greatest dimensiondimension

T3 Tumor more than 5 cm in greatest dimensionT3 Tumor more than 5 cm in greatest dimension T4a Extension to chest wall not including pectoralis muscleT4a Extension to chest wall not including pectoralis muscle

T4b Edema (including peau dorange) or ulceration of the skin of the T4b Edema (including peau dorange) or ulceration of the skin of the breast or satellite skin nodules confined to the same breast breast or satellite skin nodules confined to the same breast

T4c Both T4a and T4bT4c Both T4a and T4b

T4d Inflammatory carcinomaT4d Inflammatory carcinoma

Regional Lymph Nodes (N) Regional Lymph Nodes (N) NX Regional lymph nodes cannot be assessed (eg NX Regional lymph nodes cannot be assessed (eg

previously removed) previously removed) N0 No regional lymph node metastasisN0 No regional lymph node metastasis N1 Metastasis to movable ipsilateral axillary lymph N1 Metastasis to movable ipsilateral axillary lymph

node(s)node(s) N2 N2

N2a Metastases in ipsilateral axillary lymph nodes N2a Metastases in ipsilateral axillary lymph nodes fixed to one another (matted) or to other structures fixed to one another (matted) or to other structures

N2b Metastasis only in N2b Metastasis only in clinically apparentclinically apparent ipsilateral ipsilateral internal mammary nodes and in theinternal mammary nodes and in the absence absence of of clinically evident axillary lymph node metastasis clinically evident axillary lymph node metastasis

N3N3

N3a Metastasis in ipsilateral infraclavicular lymph N3a Metastasis in ipsilateral infraclavicular lymph node(s)node(s)

N3b Metastasis in ipsilateral internal mammary N3b Metastasis in ipsilateral internal mammary lymph node(s) and axillary lymph node(s) lymph node(s) and axillary lymph node(s)

N3c Metastasis in ipsilateral supraclavicular lymph N3c Metastasis in ipsilateral supraclavicular lymph node(s)node(s)

M ( METASTASIS)M ( METASTASIS)

MX metastasis can no be assessedMX metastasis can no be assessed

M0 no metastasisM0 no metastasis

M1 metastasisM1 metastasis

American Cancer SocietyAmerican Cancer SocietyScreening RecommendationsScreening Recommendations

Annual mammogramsAnnual mammograms starting at starting at age 40age 40

Clinical breast examsClinical breast examsndash every year starting at age 40every year starting at age 40ndash every 3 years for women age every 3 years for women age 20-3920-39

Self-breast examsSelf-breast exams monthly starting monthly starting at age 20at age 20

Breast Self-Exam ndash Step Breast Self-Exam ndash Step 11 Begin by looking at your breasts in the mirror Begin by looking at your breasts in the mirror

with your shoulders straight and yourwith your shoulders straight and your

arms on your hipsarms on your hips Heres what you should look forHeres what you should look for

Breasts that are their usual size shape and colorBreasts that are their usual size shape and color

--Breasts that are evenly shaped without visible --Breasts that are evenly shaped without visible distortion or swellingdistortion or swelling

If you see any of the following changes bring If you see any of the following changes bring them to your doctors attentionthem to your doctors attention

--Dimpling puckering or bulging of the skin--Dimpling puckering or bulging of the skin

--A nipple that has changed position or become --A nipple that has changed position or become inverted (pushed inward instead ofinverted (pushed inward instead of

sticking out)sticking out) --Redness soreness rash or swelling--Redness soreness rash or swelling

Breast Self-Exam ndash Step Breast Self-Exam ndash Step 22

Raise your arms and look for the Raise your arms and look for the

samesame

changeschanges

Breast Self-Exam ndash Step Breast Self-Exam ndash Step 33 Feel your breasts while lying down using Feel your breasts while lying down using

your right hand to feel your left breast and your right hand to feel your left breast and then your left hand to feel your right breast then your left hand to feel your right breast Use a firm smooth touch with the first few Use a firm smooth touch with the first few fingers of your hand keeping the fingersfingers of your hand keeping the fingers

flat and togetherflat and together

Cover the entire breast from top to Cover the entire breast from top to bottom side to sidemdashfrom your bottom side to sidemdashfrom your collarbone to the top of your abdomen collarbone to the top of your abdomen and from your armpit to your cleavageand from your armpit to your cleavage

Breast Self-Exam ndash Step Breast Self-Exam ndash Step 44

Finally feel your breasts while you are Finally feel your breasts while you are standing or sitting Many women find standing or sitting Many women find that the easiest way to feel their breasts that the easiest way to feel their breasts is when their skin is wet and slippery is when their skin is wet and slippery so they like to do this step in the so they like to do this step in the shower Cover your entire breast using shower Cover your entire breast using the same hand movements described in the same hand movements described in Step 3Step 3

InvestigationsInvestigations

Mammography (conrsquot)Mammography (conrsquot) 1048698 1048698 Standard mammography Standard mammography depends on depends on

density of the tissue and its ability to stop density of the tissue and its ability to stop xrayxray

beam from exposing film placed on the other beam from exposing film placed on the other side of the breastside of the breast

Digital mammography Digital mammography works on the same works on the same principle but there is also some ability to principle but there is also some ability to manipulate the image by computer Main manipulate the image by computer Main advantage is storage of the filmsadvantage is storage of the films

UltrasoundUltrasound

Since solid tissue andSince solid tissue and collections of fluid look thecollections of fluid look the same on mammographysame on mammography ultrasound is very useful in ultrasound is very useful in telling whether a mass istelling whether a mass is solid or fluid and if solid ifsolid or fluid and if solid if characteristics arecharacteristics are suspicioussuspicious CystCyst

MRIMRI MRI relies on completely different type of MRI relies on completely different type of

wavewave

energy a strong magnet that affects the energy a strong magnet that affects the charge incharge in

the nuclei As magnetic force is applied and the nuclei As magnetic force is applied and thenthen

released different types of tissue send back released different types of tissue send back different types of radio wavesdifferent types of radio waves

MRI can be extremely useful in very denseMRI can be extremely useful in very dense

breasts hereditary casesbreasts hereditary cases

Fine needle aspiration of a palpable mass

1048698 Fine needle aspiration takes individual cells out ofmass Can be done for palpable or non-palpablemasses Does not show architecture especially wallof duct so best used to confirm strong suspicions

Fine Needle Aspiration

C0 No epithelial cellsC1 InadequateC2 BenignC3 AtypiaC4 SuspiciousC5 Malignant

1048698 Core biopsy can also bedone on palpable and non palpableabnormalities and on microcalcifications

Core Biopsy

B1 Normal tissue unsatisfactoryB2 BenignB3 Lesion uncertain malignant potentialB4 Suspicion of malignancyB5a In situ malignancyB5b Invasive malignancy

Investigations for Investigations for metastasismetastasis

1- abdominal ultrasound1- abdominal ultrasound

2- chest x ray or CT2- chest x ray or CT

3- bone survey or bone scan3- bone survey or bone scan

Established prognostic Established prognostic factorsfactors

bull Nodal status Nodal status bull Tumor size Tumor size bull Lymph node Lymph node bull Grade Grade bull ERPR StatusERPR Statusbull Age Age bull Lymphatic invasionLymphatic invasionbull Histological tumor typeHistological tumor type bull Perinodular infiltrationPerinodular infiltration

TREATMENT OPTIONS FOR PRIMARY OPERABLE BREAST CANCER Objective Options

Local control Lumpectomy Lumpectomy with breast irradiation Mastectomy

Regional control Axillary lymph node dissection Regional irradiation

Control of occult Chemotherapymicrometastatic disease Hormone therapy

Improved function and cosmesis Breast-conserving therapy Reconstruction (immediate or delayed)

Localized breast cancer Surgery is mainstay Halsted 1882 radical mastectomy

John Hopkins

Metastatic breast cancer Systemic treatment

Radical mastectomy A Entire breast and a

chest wall muscle is removed

LNs in the level 1 (B) and level 2 (C ) and even sometimes more distant lymph node groups (D E and F) were also removed

Modified radical mastectomy (MRM)

A Entire breast is removed

Classically some lymph nodes in the level 1 (B) and level 2 (C ) were removed called an axillary lymph node dissection

MRM = simple mastectomy + ALND

Breast conserving surgery

Also called lumpectomy with safety margin with axillary clearance or sentinel lymph node biopsy

RT should be followed

Adjuvant systemic treatment

Hypothesis Eradicate micrometastasis From effective treatment for overt

(macro) metastasis

Chemotherapy Hormone therapy

Adjuvant chemotherapy

CMF first generation 1970s Cyclophosphamide Methotrexate 5-FU

Benefit in Distant recurrence Survival

Adjuvant chemotherapy

CAF or CEF 2nd generation 1980s Cyclophophamide Adramycin(or Epirubicin) 5-FU

More toxic than CMF CAF better than CMF in high-risk group

Axilla LN+ LN- but tumor large or other risk factor

Adjuvant chemotherapy

Incorporate Taxane TAC 3rd generation mid-1990s

Taxotere Adriamycin Cyclophosphamide

More toxic than CAF Better than CAF in high-risk group

Need more time to observe

Adjuvant Herceptin(HER-2 (Human Epidermal growth factor Receptor 2) also

known as proto-oncogene Neu Over expression of this gene is correlated with higher aggressiveness in breast cancer

HER2 is a cell membrane surface-bound receptor tyrosine kinase and is normally involved in the signal transduction pathways leading to cell growth and differentiation)

Effective in Her2+ pts ICH3+ FISH+

Herceptin + adjuvant chemotherapy Optimal role to be defined

Concurrent or sequential Maintenance Duration

SpreadSpreadDirect spread-Direct spread-

11 Intrinsic Intrinsic to surrounding breast tissue to surrounding breast tissue

2 2 ExtrinsicExtrinsic

To the skin causing ulceration amp To the skin causing ulceration amp fungation fungation

To deep structures Pectoral fascia To deep structures Pectoral fascia pectoral muscles amp chest wallpectoral muscles amp chest wall

Lymphatic spread-Lymphatic spread-

Haematogenous spread- Haematogenous spread-

Transcoelomic spread-Transcoelomic spread-

Clinical pictureClinical picture Symptoms Symptoms

A- AsymptomaticA- Asymptomatic- - discovered discovered accidentally during screening programs accidentally during screening programs

B- SymptomaticB- Symptomatic- -

1 Mass 1 Mass ((commonest presentationcommonest presentation) )

2 Pain2 Pain ( (Very Rare 10Very Rare 10))

3 Nipple discharge 3 Nipple discharge - Bloody discharge - Bloody discharge in duct carcinoma in duct carcinoma

4 Skin amp nipple manifestations4 Skin amp nipple manifestations

5 Manifestations of metastasis- 5 Manifestations of metastasis-

Signs Signs

A) General examinationsA) General examinations

1 Chest signs of pleural effusion or 1 Chest signs of pleural effusion or mediastinal LNmediastinal LN

2 Abdominal examination2 Abdominal examination

- Hepatomegaly - Ascites- Hepatomegaly - Ascites

3 PR or PV nodules in the 3 PR or PV nodules in the Douglasrsquo pouch or Krukenbergrsquos Douglasrsquo pouch or Krukenbergrsquos tumortumor

4 Bone for tenderness swelling amp 4 Bone for tenderness swelling amp pathological fracturepathological fracture

B) Local examinationB) Local examination

1- inspection1- inspection

BreastBreast compared to healthy side compared to healthy side

Nipple amp areola Nipple amp areola may showmay show

the skinthe skin

1) Skin dimpling Tethering amp Puckering1) Skin dimpling Tethering amp Puckering

2) ulceration amp fungation 2) ulceration amp fungation

3) Peau drsquoorange (Pitted edema) 3) Peau drsquoorange (Pitted edema)

4) Cancerous satellite nodules (late sign) 4) Cancerous satellite nodules (late sign)

5) Cancer en cuirasse5) Cancer en cuirasse

The massThe mass the axillathe axilla The armThe arm

2- palpation2- palpation palpate breasts with both the flat of your palpate breasts with both the flat of your

hand and fingers hand and fingers with flat fingers compress breast tissue with flat fingers compress breast tissue follow systematically in a circular follow systematically in a circular

pattern around the nipple or along the pattern around the nipple or along the radial lines (simulate a clock) or vertical radial lines (simulate a clock) or vertical segments and feel the entire breast segments and feel the entire breast including the tail near the axillaincluding the tail near the axilla

Examine criteria of the mass site size shape consistency

Examine axillary lymph nodes

American Joint Committee on Cancer TNM Staging System for Breast American Joint Committee on Cancer TNM Staging System for Breast Cancer Cancer

Primary Tumor (T)Primary Tumor (T) TX Primary tumor cannot be assessedTX Primary tumor cannot be assessed T0 No evidence of primary tumorT0 No evidence of primary tumor Tis Carcinoma Tis Carcinoma in situin situ

Note Pagets disease associated with a tumor is classified according Note Pagets disease associated with a tumor is classified according to the size of the tumor to the size of the tumor

T1 Tumor 2 cm or less in greatest dimensionT1 Tumor 2 cm or less in greatest dimension

T1mic Microinvasion 01 cm or less in greatest dimensionT1mic Microinvasion 01 cm or less in greatest dimension

T1a Tumor more than 01 cm but not more than 05 cm in greatest T1a Tumor more than 01 cm but not more than 05 cm in greatest dimension dimension

T1b Tumor more than 05 cm but not more than 1 cm in greatest T1b Tumor more than 05 cm but not more than 1 cm in greatest dimension dimension

T1c Tumor more than 1 cm but not more than 2 cm in greatest T1c Tumor more than 1 cm but not more than 2 cm in greatest dimensiondimension

T2 Tumor more than 2 cm but not more than 5 cm in greatest T2 Tumor more than 2 cm but not more than 5 cm in greatest dimensiondimension

T3 Tumor more than 5 cm in greatest dimensionT3 Tumor more than 5 cm in greatest dimension T4a Extension to chest wall not including pectoralis muscleT4a Extension to chest wall not including pectoralis muscle

T4b Edema (including peau dorange) or ulceration of the skin of the T4b Edema (including peau dorange) or ulceration of the skin of the breast or satellite skin nodules confined to the same breast breast or satellite skin nodules confined to the same breast

T4c Both T4a and T4bT4c Both T4a and T4b

T4d Inflammatory carcinomaT4d Inflammatory carcinoma

Regional Lymph Nodes (N) Regional Lymph Nodes (N) NX Regional lymph nodes cannot be assessed (eg NX Regional lymph nodes cannot be assessed (eg

previously removed) previously removed) N0 No regional lymph node metastasisN0 No regional lymph node metastasis N1 Metastasis to movable ipsilateral axillary lymph N1 Metastasis to movable ipsilateral axillary lymph

node(s)node(s) N2 N2

N2a Metastases in ipsilateral axillary lymph nodes N2a Metastases in ipsilateral axillary lymph nodes fixed to one another (matted) or to other structures fixed to one another (matted) or to other structures

N2b Metastasis only in N2b Metastasis only in clinically apparentclinically apparent ipsilateral ipsilateral internal mammary nodes and in theinternal mammary nodes and in the absence absence of of clinically evident axillary lymph node metastasis clinically evident axillary lymph node metastasis

N3N3

N3a Metastasis in ipsilateral infraclavicular lymph N3a Metastasis in ipsilateral infraclavicular lymph node(s)node(s)

N3b Metastasis in ipsilateral internal mammary N3b Metastasis in ipsilateral internal mammary lymph node(s) and axillary lymph node(s) lymph node(s) and axillary lymph node(s)

N3c Metastasis in ipsilateral supraclavicular lymph N3c Metastasis in ipsilateral supraclavicular lymph node(s)node(s)

M ( METASTASIS)M ( METASTASIS)

MX metastasis can no be assessedMX metastasis can no be assessed

M0 no metastasisM0 no metastasis

M1 metastasisM1 metastasis

American Cancer SocietyAmerican Cancer SocietyScreening RecommendationsScreening Recommendations

Annual mammogramsAnnual mammograms starting at starting at age 40age 40

Clinical breast examsClinical breast examsndash every year starting at age 40every year starting at age 40ndash every 3 years for women age every 3 years for women age 20-3920-39

Self-breast examsSelf-breast exams monthly starting monthly starting at age 20at age 20

Breast Self-Exam ndash Step Breast Self-Exam ndash Step 11 Begin by looking at your breasts in the mirror Begin by looking at your breasts in the mirror

with your shoulders straight and yourwith your shoulders straight and your

arms on your hipsarms on your hips Heres what you should look forHeres what you should look for

Breasts that are their usual size shape and colorBreasts that are their usual size shape and color

--Breasts that are evenly shaped without visible --Breasts that are evenly shaped without visible distortion or swellingdistortion or swelling

If you see any of the following changes bring If you see any of the following changes bring them to your doctors attentionthem to your doctors attention

--Dimpling puckering or bulging of the skin--Dimpling puckering or bulging of the skin

--A nipple that has changed position or become --A nipple that has changed position or become inverted (pushed inward instead ofinverted (pushed inward instead of

sticking out)sticking out) --Redness soreness rash or swelling--Redness soreness rash or swelling

Breast Self-Exam ndash Step Breast Self-Exam ndash Step 22

Raise your arms and look for the Raise your arms and look for the

samesame

changeschanges

Breast Self-Exam ndash Step Breast Self-Exam ndash Step 33 Feel your breasts while lying down using Feel your breasts while lying down using

your right hand to feel your left breast and your right hand to feel your left breast and then your left hand to feel your right breast then your left hand to feel your right breast Use a firm smooth touch with the first few Use a firm smooth touch with the first few fingers of your hand keeping the fingersfingers of your hand keeping the fingers

flat and togetherflat and together

Cover the entire breast from top to Cover the entire breast from top to bottom side to sidemdashfrom your bottom side to sidemdashfrom your collarbone to the top of your abdomen collarbone to the top of your abdomen and from your armpit to your cleavageand from your armpit to your cleavage

Breast Self-Exam ndash Step Breast Self-Exam ndash Step 44

Finally feel your breasts while you are Finally feel your breasts while you are standing or sitting Many women find standing or sitting Many women find that the easiest way to feel their breasts that the easiest way to feel their breasts is when their skin is wet and slippery is when their skin is wet and slippery so they like to do this step in the so they like to do this step in the shower Cover your entire breast using shower Cover your entire breast using the same hand movements described in the same hand movements described in Step 3Step 3

InvestigationsInvestigations

Mammography (conrsquot)Mammography (conrsquot) 1048698 1048698 Standard mammography Standard mammography depends on depends on

density of the tissue and its ability to stop density of the tissue and its ability to stop xrayxray

beam from exposing film placed on the other beam from exposing film placed on the other side of the breastside of the breast

Digital mammography Digital mammography works on the same works on the same principle but there is also some ability to principle but there is also some ability to manipulate the image by computer Main manipulate the image by computer Main advantage is storage of the filmsadvantage is storage of the films

UltrasoundUltrasound

Since solid tissue andSince solid tissue and collections of fluid look thecollections of fluid look the same on mammographysame on mammography ultrasound is very useful in ultrasound is very useful in telling whether a mass istelling whether a mass is solid or fluid and if solid ifsolid or fluid and if solid if characteristics arecharacteristics are suspicioussuspicious CystCyst

MRIMRI MRI relies on completely different type of MRI relies on completely different type of

wavewave

energy a strong magnet that affects the energy a strong magnet that affects the charge incharge in

the nuclei As magnetic force is applied and the nuclei As magnetic force is applied and thenthen

released different types of tissue send back released different types of tissue send back different types of radio wavesdifferent types of radio waves

MRI can be extremely useful in very denseMRI can be extremely useful in very dense

breasts hereditary casesbreasts hereditary cases

Fine needle aspiration of a palpable mass

1048698 Fine needle aspiration takes individual cells out ofmass Can be done for palpable or non-palpablemasses Does not show architecture especially wallof duct so best used to confirm strong suspicions

Fine Needle Aspiration

C0 No epithelial cellsC1 InadequateC2 BenignC3 AtypiaC4 SuspiciousC5 Malignant

1048698 Core biopsy can also bedone on palpable and non palpableabnormalities and on microcalcifications

Core Biopsy

B1 Normal tissue unsatisfactoryB2 BenignB3 Lesion uncertain malignant potentialB4 Suspicion of malignancyB5a In situ malignancyB5b Invasive malignancy

Investigations for Investigations for metastasismetastasis

1- abdominal ultrasound1- abdominal ultrasound

2- chest x ray or CT2- chest x ray or CT

3- bone survey or bone scan3- bone survey or bone scan

Established prognostic Established prognostic factorsfactors

bull Nodal status Nodal status bull Tumor size Tumor size bull Lymph node Lymph node bull Grade Grade bull ERPR StatusERPR Statusbull Age Age bull Lymphatic invasionLymphatic invasionbull Histological tumor typeHistological tumor type bull Perinodular infiltrationPerinodular infiltration

TREATMENT OPTIONS FOR PRIMARY OPERABLE BREAST CANCER Objective Options

Local control Lumpectomy Lumpectomy with breast irradiation Mastectomy

Regional control Axillary lymph node dissection Regional irradiation

Control of occult Chemotherapymicrometastatic disease Hormone therapy

Improved function and cosmesis Breast-conserving therapy Reconstruction (immediate or delayed)

Localized breast cancer Surgery is mainstay Halsted 1882 radical mastectomy

John Hopkins

Metastatic breast cancer Systemic treatment

Radical mastectomy A Entire breast and a

chest wall muscle is removed

LNs in the level 1 (B) and level 2 (C ) and even sometimes more distant lymph node groups (D E and F) were also removed

Modified radical mastectomy (MRM)

A Entire breast is removed

Classically some lymph nodes in the level 1 (B) and level 2 (C ) were removed called an axillary lymph node dissection

MRM = simple mastectomy + ALND

Breast conserving surgery

Also called lumpectomy with safety margin with axillary clearance or sentinel lymph node biopsy

RT should be followed

Adjuvant systemic treatment

Hypothesis Eradicate micrometastasis From effective treatment for overt

(macro) metastasis

Chemotherapy Hormone therapy

Adjuvant chemotherapy

CMF first generation 1970s Cyclophosphamide Methotrexate 5-FU

Benefit in Distant recurrence Survival

Adjuvant chemotherapy

CAF or CEF 2nd generation 1980s Cyclophophamide Adramycin(or Epirubicin) 5-FU

More toxic than CMF CAF better than CMF in high-risk group

Axilla LN+ LN- but tumor large or other risk factor

Adjuvant chemotherapy

Incorporate Taxane TAC 3rd generation mid-1990s

Taxotere Adriamycin Cyclophosphamide

More toxic than CAF Better than CAF in high-risk group

Need more time to observe

Adjuvant Herceptin(HER-2 (Human Epidermal growth factor Receptor 2) also

known as proto-oncogene Neu Over expression of this gene is correlated with higher aggressiveness in breast cancer

HER2 is a cell membrane surface-bound receptor tyrosine kinase and is normally involved in the signal transduction pathways leading to cell growth and differentiation)

Effective in Her2+ pts ICH3+ FISH+

Herceptin + adjuvant chemotherapy Optimal role to be defined

Concurrent or sequential Maintenance Duration

Clinical pictureClinical picture Symptoms Symptoms

A- AsymptomaticA- Asymptomatic- - discovered discovered accidentally during screening programs accidentally during screening programs

B- SymptomaticB- Symptomatic- -

1 Mass 1 Mass ((commonest presentationcommonest presentation) )

2 Pain2 Pain ( (Very Rare 10Very Rare 10))

3 Nipple discharge 3 Nipple discharge - Bloody discharge - Bloody discharge in duct carcinoma in duct carcinoma

4 Skin amp nipple manifestations4 Skin amp nipple manifestations

5 Manifestations of metastasis- 5 Manifestations of metastasis-

Signs Signs

A) General examinationsA) General examinations

1 Chest signs of pleural effusion or 1 Chest signs of pleural effusion or mediastinal LNmediastinal LN

2 Abdominal examination2 Abdominal examination

- Hepatomegaly - Ascites- Hepatomegaly - Ascites

3 PR or PV nodules in the 3 PR or PV nodules in the Douglasrsquo pouch or Krukenbergrsquos Douglasrsquo pouch or Krukenbergrsquos tumortumor

4 Bone for tenderness swelling amp 4 Bone for tenderness swelling amp pathological fracturepathological fracture

B) Local examinationB) Local examination

1- inspection1- inspection

BreastBreast compared to healthy side compared to healthy side

Nipple amp areola Nipple amp areola may showmay show

the skinthe skin

1) Skin dimpling Tethering amp Puckering1) Skin dimpling Tethering amp Puckering

2) ulceration amp fungation 2) ulceration amp fungation

3) Peau drsquoorange (Pitted edema) 3) Peau drsquoorange (Pitted edema)

4) Cancerous satellite nodules (late sign) 4) Cancerous satellite nodules (late sign)

5) Cancer en cuirasse5) Cancer en cuirasse

The massThe mass the axillathe axilla The armThe arm

2- palpation2- palpation palpate breasts with both the flat of your palpate breasts with both the flat of your

hand and fingers hand and fingers with flat fingers compress breast tissue with flat fingers compress breast tissue follow systematically in a circular follow systematically in a circular

pattern around the nipple or along the pattern around the nipple or along the radial lines (simulate a clock) or vertical radial lines (simulate a clock) or vertical segments and feel the entire breast segments and feel the entire breast including the tail near the axillaincluding the tail near the axilla

Examine criteria of the mass site size shape consistency

Examine axillary lymph nodes

American Joint Committee on Cancer TNM Staging System for Breast American Joint Committee on Cancer TNM Staging System for Breast Cancer Cancer

Primary Tumor (T)Primary Tumor (T) TX Primary tumor cannot be assessedTX Primary tumor cannot be assessed T0 No evidence of primary tumorT0 No evidence of primary tumor Tis Carcinoma Tis Carcinoma in situin situ

Note Pagets disease associated with a tumor is classified according Note Pagets disease associated with a tumor is classified according to the size of the tumor to the size of the tumor

T1 Tumor 2 cm or less in greatest dimensionT1 Tumor 2 cm or less in greatest dimension

T1mic Microinvasion 01 cm or less in greatest dimensionT1mic Microinvasion 01 cm or less in greatest dimension

T1a Tumor more than 01 cm but not more than 05 cm in greatest T1a Tumor more than 01 cm but not more than 05 cm in greatest dimension dimension

T1b Tumor more than 05 cm but not more than 1 cm in greatest T1b Tumor more than 05 cm but not more than 1 cm in greatest dimension dimension

T1c Tumor more than 1 cm but not more than 2 cm in greatest T1c Tumor more than 1 cm but not more than 2 cm in greatest dimensiondimension

T2 Tumor more than 2 cm but not more than 5 cm in greatest T2 Tumor more than 2 cm but not more than 5 cm in greatest dimensiondimension

T3 Tumor more than 5 cm in greatest dimensionT3 Tumor more than 5 cm in greatest dimension T4a Extension to chest wall not including pectoralis muscleT4a Extension to chest wall not including pectoralis muscle

T4b Edema (including peau dorange) or ulceration of the skin of the T4b Edema (including peau dorange) or ulceration of the skin of the breast or satellite skin nodules confined to the same breast breast or satellite skin nodules confined to the same breast

T4c Both T4a and T4bT4c Both T4a and T4b

T4d Inflammatory carcinomaT4d Inflammatory carcinoma

Regional Lymph Nodes (N) Regional Lymph Nodes (N) NX Regional lymph nodes cannot be assessed (eg NX Regional lymph nodes cannot be assessed (eg

previously removed) previously removed) N0 No regional lymph node metastasisN0 No regional lymph node metastasis N1 Metastasis to movable ipsilateral axillary lymph N1 Metastasis to movable ipsilateral axillary lymph

node(s)node(s) N2 N2

N2a Metastases in ipsilateral axillary lymph nodes N2a Metastases in ipsilateral axillary lymph nodes fixed to one another (matted) or to other structures fixed to one another (matted) or to other structures

N2b Metastasis only in N2b Metastasis only in clinically apparentclinically apparent ipsilateral ipsilateral internal mammary nodes and in theinternal mammary nodes and in the absence absence of of clinically evident axillary lymph node metastasis clinically evident axillary lymph node metastasis

N3N3

N3a Metastasis in ipsilateral infraclavicular lymph N3a Metastasis in ipsilateral infraclavicular lymph node(s)node(s)

N3b Metastasis in ipsilateral internal mammary N3b Metastasis in ipsilateral internal mammary lymph node(s) and axillary lymph node(s) lymph node(s) and axillary lymph node(s)

N3c Metastasis in ipsilateral supraclavicular lymph N3c Metastasis in ipsilateral supraclavicular lymph node(s)node(s)

M ( METASTASIS)M ( METASTASIS)

MX metastasis can no be assessedMX metastasis can no be assessed

M0 no metastasisM0 no metastasis

M1 metastasisM1 metastasis

American Cancer SocietyAmerican Cancer SocietyScreening RecommendationsScreening Recommendations

Annual mammogramsAnnual mammograms starting at starting at age 40age 40

Clinical breast examsClinical breast examsndash every year starting at age 40every year starting at age 40ndash every 3 years for women age every 3 years for women age 20-3920-39

Self-breast examsSelf-breast exams monthly starting monthly starting at age 20at age 20

Breast Self-Exam ndash Step Breast Self-Exam ndash Step 11 Begin by looking at your breasts in the mirror Begin by looking at your breasts in the mirror

with your shoulders straight and yourwith your shoulders straight and your

arms on your hipsarms on your hips Heres what you should look forHeres what you should look for

Breasts that are their usual size shape and colorBreasts that are their usual size shape and color

--Breasts that are evenly shaped without visible --Breasts that are evenly shaped without visible distortion or swellingdistortion or swelling

If you see any of the following changes bring If you see any of the following changes bring them to your doctors attentionthem to your doctors attention

--Dimpling puckering or bulging of the skin--Dimpling puckering or bulging of the skin

--A nipple that has changed position or become --A nipple that has changed position or become inverted (pushed inward instead ofinverted (pushed inward instead of

sticking out)sticking out) --Redness soreness rash or swelling--Redness soreness rash or swelling

Breast Self-Exam ndash Step Breast Self-Exam ndash Step 22

Raise your arms and look for the Raise your arms and look for the

samesame

changeschanges

Breast Self-Exam ndash Step Breast Self-Exam ndash Step 33 Feel your breasts while lying down using Feel your breasts while lying down using

your right hand to feel your left breast and your right hand to feel your left breast and then your left hand to feel your right breast then your left hand to feel your right breast Use a firm smooth touch with the first few Use a firm smooth touch with the first few fingers of your hand keeping the fingersfingers of your hand keeping the fingers

flat and togetherflat and together

Cover the entire breast from top to Cover the entire breast from top to bottom side to sidemdashfrom your bottom side to sidemdashfrom your collarbone to the top of your abdomen collarbone to the top of your abdomen and from your armpit to your cleavageand from your armpit to your cleavage

Breast Self-Exam ndash Step Breast Self-Exam ndash Step 44

Finally feel your breasts while you are Finally feel your breasts while you are standing or sitting Many women find standing or sitting Many women find that the easiest way to feel their breasts that the easiest way to feel their breasts is when their skin is wet and slippery is when their skin is wet and slippery so they like to do this step in the so they like to do this step in the shower Cover your entire breast using shower Cover your entire breast using the same hand movements described in the same hand movements described in Step 3Step 3

InvestigationsInvestigations

Mammography (conrsquot)Mammography (conrsquot) 1048698 1048698 Standard mammography Standard mammography depends on depends on

density of the tissue and its ability to stop density of the tissue and its ability to stop xrayxray

beam from exposing film placed on the other beam from exposing film placed on the other side of the breastside of the breast

Digital mammography Digital mammography works on the same works on the same principle but there is also some ability to principle but there is also some ability to manipulate the image by computer Main manipulate the image by computer Main advantage is storage of the filmsadvantage is storage of the films

UltrasoundUltrasound

Since solid tissue andSince solid tissue and collections of fluid look thecollections of fluid look the same on mammographysame on mammography ultrasound is very useful in ultrasound is very useful in telling whether a mass istelling whether a mass is solid or fluid and if solid ifsolid or fluid and if solid if characteristics arecharacteristics are suspicioussuspicious CystCyst

MRIMRI MRI relies on completely different type of MRI relies on completely different type of

wavewave

energy a strong magnet that affects the energy a strong magnet that affects the charge incharge in

the nuclei As magnetic force is applied and the nuclei As magnetic force is applied and thenthen

released different types of tissue send back released different types of tissue send back different types of radio wavesdifferent types of radio waves

MRI can be extremely useful in very denseMRI can be extremely useful in very dense

breasts hereditary casesbreasts hereditary cases

Fine needle aspiration of a palpable mass

1048698 Fine needle aspiration takes individual cells out ofmass Can be done for palpable or non-palpablemasses Does not show architecture especially wallof duct so best used to confirm strong suspicions

Fine Needle Aspiration

C0 No epithelial cellsC1 InadequateC2 BenignC3 AtypiaC4 SuspiciousC5 Malignant

1048698 Core biopsy can also bedone on palpable and non palpableabnormalities and on microcalcifications

Core Biopsy

B1 Normal tissue unsatisfactoryB2 BenignB3 Lesion uncertain malignant potentialB4 Suspicion of malignancyB5a In situ malignancyB5b Invasive malignancy

Investigations for Investigations for metastasismetastasis

1- abdominal ultrasound1- abdominal ultrasound

2- chest x ray or CT2- chest x ray or CT

3- bone survey or bone scan3- bone survey or bone scan

Established prognostic Established prognostic factorsfactors

bull Nodal status Nodal status bull Tumor size Tumor size bull Lymph node Lymph node bull Grade Grade bull ERPR StatusERPR Statusbull Age Age bull Lymphatic invasionLymphatic invasionbull Histological tumor typeHistological tumor type bull Perinodular infiltrationPerinodular infiltration

TREATMENT OPTIONS FOR PRIMARY OPERABLE BREAST CANCER Objective Options

Local control Lumpectomy Lumpectomy with breast irradiation Mastectomy

Regional control Axillary lymph node dissection Regional irradiation

Control of occult Chemotherapymicrometastatic disease Hormone therapy

Improved function and cosmesis Breast-conserving therapy Reconstruction (immediate or delayed)

Localized breast cancer Surgery is mainstay Halsted 1882 radical mastectomy

John Hopkins

Metastatic breast cancer Systemic treatment

Radical mastectomy A Entire breast and a

chest wall muscle is removed

LNs in the level 1 (B) and level 2 (C ) and even sometimes more distant lymph node groups (D E and F) were also removed

Modified radical mastectomy (MRM)

A Entire breast is removed

Classically some lymph nodes in the level 1 (B) and level 2 (C ) were removed called an axillary lymph node dissection

MRM = simple mastectomy + ALND

Breast conserving surgery

Also called lumpectomy with safety margin with axillary clearance or sentinel lymph node biopsy

RT should be followed

Adjuvant systemic treatment

Hypothesis Eradicate micrometastasis From effective treatment for overt

(macro) metastasis

Chemotherapy Hormone therapy

Adjuvant chemotherapy

CMF first generation 1970s Cyclophosphamide Methotrexate 5-FU

Benefit in Distant recurrence Survival

Adjuvant chemotherapy

CAF or CEF 2nd generation 1980s Cyclophophamide Adramycin(or Epirubicin) 5-FU

More toxic than CMF CAF better than CMF in high-risk group

Axilla LN+ LN- but tumor large or other risk factor

Adjuvant chemotherapy

Incorporate Taxane TAC 3rd generation mid-1990s

Taxotere Adriamycin Cyclophosphamide

More toxic than CAF Better than CAF in high-risk group

Need more time to observe

Adjuvant Herceptin(HER-2 (Human Epidermal growth factor Receptor 2) also

known as proto-oncogene Neu Over expression of this gene is correlated with higher aggressiveness in breast cancer

HER2 is a cell membrane surface-bound receptor tyrosine kinase and is normally involved in the signal transduction pathways leading to cell growth and differentiation)

Effective in Her2+ pts ICH3+ FISH+

Herceptin + adjuvant chemotherapy Optimal role to be defined

Concurrent or sequential Maintenance Duration

Signs Signs

A) General examinationsA) General examinations

1 Chest signs of pleural effusion or 1 Chest signs of pleural effusion or mediastinal LNmediastinal LN

2 Abdominal examination2 Abdominal examination

- Hepatomegaly - Ascites- Hepatomegaly - Ascites

3 PR or PV nodules in the 3 PR or PV nodules in the Douglasrsquo pouch or Krukenbergrsquos Douglasrsquo pouch or Krukenbergrsquos tumortumor

4 Bone for tenderness swelling amp 4 Bone for tenderness swelling amp pathological fracturepathological fracture

B) Local examinationB) Local examination

1- inspection1- inspection

BreastBreast compared to healthy side compared to healthy side

Nipple amp areola Nipple amp areola may showmay show

the skinthe skin

1) Skin dimpling Tethering amp Puckering1) Skin dimpling Tethering amp Puckering

2) ulceration amp fungation 2) ulceration amp fungation

3) Peau drsquoorange (Pitted edema) 3) Peau drsquoorange (Pitted edema)

4) Cancerous satellite nodules (late sign) 4) Cancerous satellite nodules (late sign)

5) Cancer en cuirasse5) Cancer en cuirasse

The massThe mass the axillathe axilla The armThe arm

2- palpation2- palpation palpate breasts with both the flat of your palpate breasts with both the flat of your

hand and fingers hand and fingers with flat fingers compress breast tissue with flat fingers compress breast tissue follow systematically in a circular follow systematically in a circular

pattern around the nipple or along the pattern around the nipple or along the radial lines (simulate a clock) or vertical radial lines (simulate a clock) or vertical segments and feel the entire breast segments and feel the entire breast including the tail near the axillaincluding the tail near the axilla

Examine criteria of the mass site size shape consistency

Examine axillary lymph nodes

American Joint Committee on Cancer TNM Staging System for Breast American Joint Committee on Cancer TNM Staging System for Breast Cancer Cancer

Primary Tumor (T)Primary Tumor (T) TX Primary tumor cannot be assessedTX Primary tumor cannot be assessed T0 No evidence of primary tumorT0 No evidence of primary tumor Tis Carcinoma Tis Carcinoma in situin situ

Note Pagets disease associated with a tumor is classified according Note Pagets disease associated with a tumor is classified according to the size of the tumor to the size of the tumor

T1 Tumor 2 cm or less in greatest dimensionT1 Tumor 2 cm or less in greatest dimension

T1mic Microinvasion 01 cm or less in greatest dimensionT1mic Microinvasion 01 cm or less in greatest dimension

T1a Tumor more than 01 cm but not more than 05 cm in greatest T1a Tumor more than 01 cm but not more than 05 cm in greatest dimension dimension

T1b Tumor more than 05 cm but not more than 1 cm in greatest T1b Tumor more than 05 cm but not more than 1 cm in greatest dimension dimension

T1c Tumor more than 1 cm but not more than 2 cm in greatest T1c Tumor more than 1 cm but not more than 2 cm in greatest dimensiondimension

T2 Tumor more than 2 cm but not more than 5 cm in greatest T2 Tumor more than 2 cm but not more than 5 cm in greatest dimensiondimension

T3 Tumor more than 5 cm in greatest dimensionT3 Tumor more than 5 cm in greatest dimension T4a Extension to chest wall not including pectoralis muscleT4a Extension to chest wall not including pectoralis muscle

T4b Edema (including peau dorange) or ulceration of the skin of the T4b Edema (including peau dorange) or ulceration of the skin of the breast or satellite skin nodules confined to the same breast breast or satellite skin nodules confined to the same breast

T4c Both T4a and T4bT4c Both T4a and T4b

T4d Inflammatory carcinomaT4d Inflammatory carcinoma

Regional Lymph Nodes (N) Regional Lymph Nodes (N) NX Regional lymph nodes cannot be assessed (eg NX Regional lymph nodes cannot be assessed (eg

previously removed) previously removed) N0 No regional lymph node metastasisN0 No regional lymph node metastasis N1 Metastasis to movable ipsilateral axillary lymph N1 Metastasis to movable ipsilateral axillary lymph

node(s)node(s) N2 N2

N2a Metastases in ipsilateral axillary lymph nodes N2a Metastases in ipsilateral axillary lymph nodes fixed to one another (matted) or to other structures fixed to one another (matted) or to other structures

N2b Metastasis only in N2b Metastasis only in clinically apparentclinically apparent ipsilateral ipsilateral internal mammary nodes and in theinternal mammary nodes and in the absence absence of of clinically evident axillary lymph node metastasis clinically evident axillary lymph node metastasis

N3N3

N3a Metastasis in ipsilateral infraclavicular lymph N3a Metastasis in ipsilateral infraclavicular lymph node(s)node(s)

N3b Metastasis in ipsilateral internal mammary N3b Metastasis in ipsilateral internal mammary lymph node(s) and axillary lymph node(s) lymph node(s) and axillary lymph node(s)

N3c Metastasis in ipsilateral supraclavicular lymph N3c Metastasis in ipsilateral supraclavicular lymph node(s)node(s)

M ( METASTASIS)M ( METASTASIS)

MX metastasis can no be assessedMX metastasis can no be assessed

M0 no metastasisM0 no metastasis

M1 metastasisM1 metastasis

American Cancer SocietyAmerican Cancer SocietyScreening RecommendationsScreening Recommendations

Annual mammogramsAnnual mammograms starting at starting at age 40age 40

Clinical breast examsClinical breast examsndash every year starting at age 40every year starting at age 40ndash every 3 years for women age every 3 years for women age 20-3920-39

Self-breast examsSelf-breast exams monthly starting monthly starting at age 20at age 20

Breast Self-Exam ndash Step Breast Self-Exam ndash Step 11 Begin by looking at your breasts in the mirror Begin by looking at your breasts in the mirror

with your shoulders straight and yourwith your shoulders straight and your

arms on your hipsarms on your hips Heres what you should look forHeres what you should look for

Breasts that are their usual size shape and colorBreasts that are their usual size shape and color

--Breasts that are evenly shaped without visible --Breasts that are evenly shaped without visible distortion or swellingdistortion or swelling

If you see any of the following changes bring If you see any of the following changes bring them to your doctors attentionthem to your doctors attention

--Dimpling puckering or bulging of the skin--Dimpling puckering or bulging of the skin

--A nipple that has changed position or become --A nipple that has changed position or become inverted (pushed inward instead ofinverted (pushed inward instead of

sticking out)sticking out) --Redness soreness rash or swelling--Redness soreness rash or swelling

Breast Self-Exam ndash Step Breast Self-Exam ndash Step 22

Raise your arms and look for the Raise your arms and look for the

samesame

changeschanges

Breast Self-Exam ndash Step Breast Self-Exam ndash Step 33 Feel your breasts while lying down using Feel your breasts while lying down using

your right hand to feel your left breast and your right hand to feel your left breast and then your left hand to feel your right breast then your left hand to feel your right breast Use a firm smooth touch with the first few Use a firm smooth touch with the first few fingers of your hand keeping the fingersfingers of your hand keeping the fingers

flat and togetherflat and together

Cover the entire breast from top to Cover the entire breast from top to bottom side to sidemdashfrom your bottom side to sidemdashfrom your collarbone to the top of your abdomen collarbone to the top of your abdomen and from your armpit to your cleavageand from your armpit to your cleavage

Breast Self-Exam ndash Step Breast Self-Exam ndash Step 44

Finally feel your breasts while you are Finally feel your breasts while you are standing or sitting Many women find standing or sitting Many women find that the easiest way to feel their breasts that the easiest way to feel their breasts is when their skin is wet and slippery is when their skin is wet and slippery so they like to do this step in the so they like to do this step in the shower Cover your entire breast using shower Cover your entire breast using the same hand movements described in the same hand movements described in Step 3Step 3

InvestigationsInvestigations

Mammography (conrsquot)Mammography (conrsquot) 1048698 1048698 Standard mammography Standard mammography depends on depends on

density of the tissue and its ability to stop density of the tissue and its ability to stop xrayxray

beam from exposing film placed on the other beam from exposing film placed on the other side of the breastside of the breast

Digital mammography Digital mammography works on the same works on the same principle but there is also some ability to principle but there is also some ability to manipulate the image by computer Main manipulate the image by computer Main advantage is storage of the filmsadvantage is storage of the films

UltrasoundUltrasound

Since solid tissue andSince solid tissue and collections of fluid look thecollections of fluid look the same on mammographysame on mammography ultrasound is very useful in ultrasound is very useful in telling whether a mass istelling whether a mass is solid or fluid and if solid ifsolid or fluid and if solid if characteristics arecharacteristics are suspicioussuspicious CystCyst

MRIMRI MRI relies on completely different type of MRI relies on completely different type of

wavewave

energy a strong magnet that affects the energy a strong magnet that affects the charge incharge in

the nuclei As magnetic force is applied and the nuclei As magnetic force is applied and thenthen

released different types of tissue send back released different types of tissue send back different types of radio wavesdifferent types of radio waves

MRI can be extremely useful in very denseMRI can be extremely useful in very dense

breasts hereditary casesbreasts hereditary cases

Fine needle aspiration of a palpable mass

1048698 Fine needle aspiration takes individual cells out ofmass Can be done for palpable or non-palpablemasses Does not show architecture especially wallof duct so best used to confirm strong suspicions

Fine Needle Aspiration

C0 No epithelial cellsC1 InadequateC2 BenignC3 AtypiaC4 SuspiciousC5 Malignant

1048698 Core biopsy can also bedone on palpable and non palpableabnormalities and on microcalcifications

Core Biopsy

B1 Normal tissue unsatisfactoryB2 BenignB3 Lesion uncertain malignant potentialB4 Suspicion of malignancyB5a In situ malignancyB5b Invasive malignancy

Investigations for Investigations for metastasismetastasis

1- abdominal ultrasound1- abdominal ultrasound

2- chest x ray or CT2- chest x ray or CT

3- bone survey or bone scan3- bone survey or bone scan

Established prognostic Established prognostic factorsfactors

bull Nodal status Nodal status bull Tumor size Tumor size bull Lymph node Lymph node bull Grade Grade bull ERPR StatusERPR Statusbull Age Age bull Lymphatic invasionLymphatic invasionbull Histological tumor typeHistological tumor type bull Perinodular infiltrationPerinodular infiltration

TREATMENT OPTIONS FOR PRIMARY OPERABLE BREAST CANCER Objective Options

Local control Lumpectomy Lumpectomy with breast irradiation Mastectomy

Regional control Axillary lymph node dissection Regional irradiation

Control of occult Chemotherapymicrometastatic disease Hormone therapy

Improved function and cosmesis Breast-conserving therapy Reconstruction (immediate or delayed)

Localized breast cancer Surgery is mainstay Halsted 1882 radical mastectomy

John Hopkins

Metastatic breast cancer Systemic treatment

Radical mastectomy A Entire breast and a

chest wall muscle is removed

LNs in the level 1 (B) and level 2 (C ) and even sometimes more distant lymph node groups (D E and F) were also removed

Modified radical mastectomy (MRM)

A Entire breast is removed

Classically some lymph nodes in the level 1 (B) and level 2 (C ) were removed called an axillary lymph node dissection

MRM = simple mastectomy + ALND

Breast conserving surgery

Also called lumpectomy with safety margin with axillary clearance or sentinel lymph node biopsy

RT should be followed

Adjuvant systemic treatment

Hypothesis Eradicate micrometastasis From effective treatment for overt

(macro) metastasis

Chemotherapy Hormone therapy

Adjuvant chemotherapy

CMF first generation 1970s Cyclophosphamide Methotrexate 5-FU

Benefit in Distant recurrence Survival

Adjuvant chemotherapy

CAF or CEF 2nd generation 1980s Cyclophophamide Adramycin(or Epirubicin) 5-FU

More toxic than CMF CAF better than CMF in high-risk group

Axilla LN+ LN- but tumor large or other risk factor

Adjuvant chemotherapy

Incorporate Taxane TAC 3rd generation mid-1990s

Taxotere Adriamycin Cyclophosphamide

More toxic than CAF Better than CAF in high-risk group

Need more time to observe

Adjuvant Herceptin(HER-2 (Human Epidermal growth factor Receptor 2) also

known as proto-oncogene Neu Over expression of this gene is correlated with higher aggressiveness in breast cancer

HER2 is a cell membrane surface-bound receptor tyrosine kinase and is normally involved in the signal transduction pathways leading to cell growth and differentiation)

Effective in Her2+ pts ICH3+ FISH+

Herceptin + adjuvant chemotherapy Optimal role to be defined

Concurrent or sequential Maintenance Duration

B) Local examinationB) Local examination

1- inspection1- inspection

BreastBreast compared to healthy side compared to healthy side

Nipple amp areola Nipple amp areola may showmay show

the skinthe skin

1) Skin dimpling Tethering amp Puckering1) Skin dimpling Tethering amp Puckering

2) ulceration amp fungation 2) ulceration amp fungation

3) Peau drsquoorange (Pitted edema) 3) Peau drsquoorange (Pitted edema)

4) Cancerous satellite nodules (late sign) 4) Cancerous satellite nodules (late sign)

5) Cancer en cuirasse5) Cancer en cuirasse

The massThe mass the axillathe axilla The armThe arm

2- palpation2- palpation palpate breasts with both the flat of your palpate breasts with both the flat of your

hand and fingers hand and fingers with flat fingers compress breast tissue with flat fingers compress breast tissue follow systematically in a circular follow systematically in a circular

pattern around the nipple or along the pattern around the nipple or along the radial lines (simulate a clock) or vertical radial lines (simulate a clock) or vertical segments and feel the entire breast segments and feel the entire breast including the tail near the axillaincluding the tail near the axilla

Examine criteria of the mass site size shape consistency

Examine axillary lymph nodes

American Joint Committee on Cancer TNM Staging System for Breast American Joint Committee on Cancer TNM Staging System for Breast Cancer Cancer

Primary Tumor (T)Primary Tumor (T) TX Primary tumor cannot be assessedTX Primary tumor cannot be assessed T0 No evidence of primary tumorT0 No evidence of primary tumor Tis Carcinoma Tis Carcinoma in situin situ

Note Pagets disease associated with a tumor is classified according Note Pagets disease associated with a tumor is classified according to the size of the tumor to the size of the tumor

T1 Tumor 2 cm or less in greatest dimensionT1 Tumor 2 cm or less in greatest dimension

T1mic Microinvasion 01 cm or less in greatest dimensionT1mic Microinvasion 01 cm or less in greatest dimension

T1a Tumor more than 01 cm but not more than 05 cm in greatest T1a Tumor more than 01 cm but not more than 05 cm in greatest dimension dimension

T1b Tumor more than 05 cm but not more than 1 cm in greatest T1b Tumor more than 05 cm but not more than 1 cm in greatest dimension dimension

T1c Tumor more than 1 cm but not more than 2 cm in greatest T1c Tumor more than 1 cm but not more than 2 cm in greatest dimensiondimension

T2 Tumor more than 2 cm but not more than 5 cm in greatest T2 Tumor more than 2 cm but not more than 5 cm in greatest dimensiondimension

T3 Tumor more than 5 cm in greatest dimensionT3 Tumor more than 5 cm in greatest dimension T4a Extension to chest wall not including pectoralis muscleT4a Extension to chest wall not including pectoralis muscle

T4b Edema (including peau dorange) or ulceration of the skin of the T4b Edema (including peau dorange) or ulceration of the skin of the breast or satellite skin nodules confined to the same breast breast or satellite skin nodules confined to the same breast

T4c Both T4a and T4bT4c Both T4a and T4b

T4d Inflammatory carcinomaT4d Inflammatory carcinoma

Regional Lymph Nodes (N) Regional Lymph Nodes (N) NX Regional lymph nodes cannot be assessed (eg NX Regional lymph nodes cannot be assessed (eg

previously removed) previously removed) N0 No regional lymph node metastasisN0 No regional lymph node metastasis N1 Metastasis to movable ipsilateral axillary lymph N1 Metastasis to movable ipsilateral axillary lymph

node(s)node(s) N2 N2

N2a Metastases in ipsilateral axillary lymph nodes N2a Metastases in ipsilateral axillary lymph nodes fixed to one another (matted) or to other structures fixed to one another (matted) or to other structures

N2b Metastasis only in N2b Metastasis only in clinically apparentclinically apparent ipsilateral ipsilateral internal mammary nodes and in theinternal mammary nodes and in the absence absence of of clinically evident axillary lymph node metastasis clinically evident axillary lymph node metastasis

N3N3

N3a Metastasis in ipsilateral infraclavicular lymph N3a Metastasis in ipsilateral infraclavicular lymph node(s)node(s)

N3b Metastasis in ipsilateral internal mammary N3b Metastasis in ipsilateral internal mammary lymph node(s) and axillary lymph node(s) lymph node(s) and axillary lymph node(s)

N3c Metastasis in ipsilateral supraclavicular lymph N3c Metastasis in ipsilateral supraclavicular lymph node(s)node(s)

M ( METASTASIS)M ( METASTASIS)

MX metastasis can no be assessedMX metastasis can no be assessed

M0 no metastasisM0 no metastasis

M1 metastasisM1 metastasis

American Cancer SocietyAmerican Cancer SocietyScreening RecommendationsScreening Recommendations

Annual mammogramsAnnual mammograms starting at starting at age 40age 40

Clinical breast examsClinical breast examsndash every year starting at age 40every year starting at age 40ndash every 3 years for women age every 3 years for women age 20-3920-39

Self-breast examsSelf-breast exams monthly starting monthly starting at age 20at age 20

Breast Self-Exam ndash Step Breast Self-Exam ndash Step 11 Begin by looking at your breasts in the mirror Begin by looking at your breasts in the mirror

with your shoulders straight and yourwith your shoulders straight and your

arms on your hipsarms on your hips Heres what you should look forHeres what you should look for

Breasts that are their usual size shape and colorBreasts that are their usual size shape and color

--Breasts that are evenly shaped without visible --Breasts that are evenly shaped without visible distortion or swellingdistortion or swelling

If you see any of the following changes bring If you see any of the following changes bring them to your doctors attentionthem to your doctors attention

--Dimpling puckering or bulging of the skin--Dimpling puckering or bulging of the skin

--A nipple that has changed position or become --A nipple that has changed position or become inverted (pushed inward instead ofinverted (pushed inward instead of

sticking out)sticking out) --Redness soreness rash or swelling--Redness soreness rash or swelling

Breast Self-Exam ndash Step Breast Self-Exam ndash Step 22

Raise your arms and look for the Raise your arms and look for the

samesame

changeschanges

Breast Self-Exam ndash Step Breast Self-Exam ndash Step 33 Feel your breasts while lying down using Feel your breasts while lying down using

your right hand to feel your left breast and your right hand to feel your left breast and then your left hand to feel your right breast then your left hand to feel your right breast Use a firm smooth touch with the first few Use a firm smooth touch with the first few fingers of your hand keeping the fingersfingers of your hand keeping the fingers

flat and togetherflat and together

Cover the entire breast from top to Cover the entire breast from top to bottom side to sidemdashfrom your bottom side to sidemdashfrom your collarbone to the top of your abdomen collarbone to the top of your abdomen and from your armpit to your cleavageand from your armpit to your cleavage

Breast Self-Exam ndash Step Breast Self-Exam ndash Step 44

Finally feel your breasts while you are Finally feel your breasts while you are standing or sitting Many women find standing or sitting Many women find that the easiest way to feel their breasts that the easiest way to feel their breasts is when their skin is wet and slippery is when their skin is wet and slippery so they like to do this step in the so they like to do this step in the shower Cover your entire breast using shower Cover your entire breast using the same hand movements described in the same hand movements described in Step 3Step 3

InvestigationsInvestigations

Mammography (conrsquot)Mammography (conrsquot) 1048698 1048698 Standard mammography Standard mammography depends on depends on

density of the tissue and its ability to stop density of the tissue and its ability to stop xrayxray

beam from exposing film placed on the other beam from exposing film placed on the other side of the breastside of the breast

Digital mammography Digital mammography works on the same works on the same principle but there is also some ability to principle but there is also some ability to manipulate the image by computer Main manipulate the image by computer Main advantage is storage of the filmsadvantage is storage of the films

UltrasoundUltrasound

Since solid tissue andSince solid tissue and collections of fluid look thecollections of fluid look the same on mammographysame on mammography ultrasound is very useful in ultrasound is very useful in telling whether a mass istelling whether a mass is solid or fluid and if solid ifsolid or fluid and if solid if characteristics arecharacteristics are suspicioussuspicious CystCyst

MRIMRI MRI relies on completely different type of MRI relies on completely different type of

wavewave

energy a strong magnet that affects the energy a strong magnet that affects the charge incharge in

the nuclei As magnetic force is applied and the nuclei As magnetic force is applied and thenthen

released different types of tissue send back released different types of tissue send back different types of radio wavesdifferent types of radio waves

MRI can be extremely useful in very denseMRI can be extremely useful in very dense

breasts hereditary casesbreasts hereditary cases

Fine needle aspiration of a palpable mass

1048698 Fine needle aspiration takes individual cells out ofmass Can be done for palpable or non-palpablemasses Does not show architecture especially wallof duct so best used to confirm strong suspicions

Fine Needle Aspiration

C0 No epithelial cellsC1 InadequateC2 BenignC3 AtypiaC4 SuspiciousC5 Malignant

1048698 Core biopsy can also bedone on palpable and non palpableabnormalities and on microcalcifications

Core Biopsy

B1 Normal tissue unsatisfactoryB2 BenignB3 Lesion uncertain malignant potentialB4 Suspicion of malignancyB5a In situ malignancyB5b Invasive malignancy

Investigations for Investigations for metastasismetastasis

1- abdominal ultrasound1- abdominal ultrasound

2- chest x ray or CT2- chest x ray or CT

3- bone survey or bone scan3- bone survey or bone scan

Established prognostic Established prognostic factorsfactors

bull Nodal status Nodal status bull Tumor size Tumor size bull Lymph node Lymph node bull Grade Grade bull ERPR StatusERPR Statusbull Age Age bull Lymphatic invasionLymphatic invasionbull Histological tumor typeHistological tumor type bull Perinodular infiltrationPerinodular infiltration

TREATMENT OPTIONS FOR PRIMARY OPERABLE BREAST CANCER Objective Options

Local control Lumpectomy Lumpectomy with breast irradiation Mastectomy

Regional control Axillary lymph node dissection Regional irradiation

Control of occult Chemotherapymicrometastatic disease Hormone therapy

Improved function and cosmesis Breast-conserving therapy Reconstruction (immediate or delayed)

Localized breast cancer Surgery is mainstay Halsted 1882 radical mastectomy

John Hopkins

Metastatic breast cancer Systemic treatment

Radical mastectomy A Entire breast and a

chest wall muscle is removed

LNs in the level 1 (B) and level 2 (C ) and even sometimes more distant lymph node groups (D E and F) were also removed

Modified radical mastectomy (MRM)

A Entire breast is removed

Classically some lymph nodes in the level 1 (B) and level 2 (C ) were removed called an axillary lymph node dissection

MRM = simple mastectomy + ALND

Breast conserving surgery

Also called lumpectomy with safety margin with axillary clearance or sentinel lymph node biopsy

RT should be followed

Adjuvant systemic treatment

Hypothesis Eradicate micrometastasis From effective treatment for overt

(macro) metastasis

Chemotherapy Hormone therapy

Adjuvant chemotherapy

CMF first generation 1970s Cyclophosphamide Methotrexate 5-FU

Benefit in Distant recurrence Survival

Adjuvant chemotherapy

CAF or CEF 2nd generation 1980s Cyclophophamide Adramycin(or Epirubicin) 5-FU

More toxic than CMF CAF better than CMF in high-risk group

Axilla LN+ LN- but tumor large or other risk factor

Adjuvant chemotherapy

Incorporate Taxane TAC 3rd generation mid-1990s

Taxotere Adriamycin Cyclophosphamide

More toxic than CAF Better than CAF in high-risk group

Need more time to observe

Adjuvant Herceptin(HER-2 (Human Epidermal growth factor Receptor 2) also

known as proto-oncogene Neu Over expression of this gene is correlated with higher aggressiveness in breast cancer

HER2 is a cell membrane surface-bound receptor tyrosine kinase and is normally involved in the signal transduction pathways leading to cell growth and differentiation)

Effective in Her2+ pts ICH3+ FISH+

Herceptin + adjuvant chemotherapy Optimal role to be defined

Concurrent or sequential Maintenance Duration

2- palpation2- palpation palpate breasts with both the flat of your palpate breasts with both the flat of your

hand and fingers hand and fingers with flat fingers compress breast tissue with flat fingers compress breast tissue follow systematically in a circular follow systematically in a circular

pattern around the nipple or along the pattern around the nipple or along the radial lines (simulate a clock) or vertical radial lines (simulate a clock) or vertical segments and feel the entire breast segments and feel the entire breast including the tail near the axillaincluding the tail near the axilla

Examine criteria of the mass site size shape consistency

Examine axillary lymph nodes

American Joint Committee on Cancer TNM Staging System for Breast American Joint Committee on Cancer TNM Staging System for Breast Cancer Cancer

Primary Tumor (T)Primary Tumor (T) TX Primary tumor cannot be assessedTX Primary tumor cannot be assessed T0 No evidence of primary tumorT0 No evidence of primary tumor Tis Carcinoma Tis Carcinoma in situin situ

Note Pagets disease associated with a tumor is classified according Note Pagets disease associated with a tumor is classified according to the size of the tumor to the size of the tumor

T1 Tumor 2 cm or less in greatest dimensionT1 Tumor 2 cm or less in greatest dimension

T1mic Microinvasion 01 cm or less in greatest dimensionT1mic Microinvasion 01 cm or less in greatest dimension

T1a Tumor more than 01 cm but not more than 05 cm in greatest T1a Tumor more than 01 cm but not more than 05 cm in greatest dimension dimension

T1b Tumor more than 05 cm but not more than 1 cm in greatest T1b Tumor more than 05 cm but not more than 1 cm in greatest dimension dimension

T1c Tumor more than 1 cm but not more than 2 cm in greatest T1c Tumor more than 1 cm but not more than 2 cm in greatest dimensiondimension

T2 Tumor more than 2 cm but not more than 5 cm in greatest T2 Tumor more than 2 cm but not more than 5 cm in greatest dimensiondimension

T3 Tumor more than 5 cm in greatest dimensionT3 Tumor more than 5 cm in greatest dimension T4a Extension to chest wall not including pectoralis muscleT4a Extension to chest wall not including pectoralis muscle

T4b Edema (including peau dorange) or ulceration of the skin of the T4b Edema (including peau dorange) or ulceration of the skin of the breast or satellite skin nodules confined to the same breast breast or satellite skin nodules confined to the same breast

T4c Both T4a and T4bT4c Both T4a and T4b

T4d Inflammatory carcinomaT4d Inflammatory carcinoma

Regional Lymph Nodes (N) Regional Lymph Nodes (N) NX Regional lymph nodes cannot be assessed (eg NX Regional lymph nodes cannot be assessed (eg

previously removed) previously removed) N0 No regional lymph node metastasisN0 No regional lymph node metastasis N1 Metastasis to movable ipsilateral axillary lymph N1 Metastasis to movable ipsilateral axillary lymph

node(s)node(s) N2 N2

N2a Metastases in ipsilateral axillary lymph nodes N2a Metastases in ipsilateral axillary lymph nodes fixed to one another (matted) or to other structures fixed to one another (matted) or to other structures

N2b Metastasis only in N2b Metastasis only in clinically apparentclinically apparent ipsilateral ipsilateral internal mammary nodes and in theinternal mammary nodes and in the absence absence of of clinically evident axillary lymph node metastasis clinically evident axillary lymph node metastasis

N3N3

N3a Metastasis in ipsilateral infraclavicular lymph N3a Metastasis in ipsilateral infraclavicular lymph node(s)node(s)

N3b Metastasis in ipsilateral internal mammary N3b Metastasis in ipsilateral internal mammary lymph node(s) and axillary lymph node(s) lymph node(s) and axillary lymph node(s)

N3c Metastasis in ipsilateral supraclavicular lymph N3c Metastasis in ipsilateral supraclavicular lymph node(s)node(s)

M ( METASTASIS)M ( METASTASIS)

MX metastasis can no be assessedMX metastasis can no be assessed

M0 no metastasisM0 no metastasis

M1 metastasisM1 metastasis

American Cancer SocietyAmerican Cancer SocietyScreening RecommendationsScreening Recommendations

Annual mammogramsAnnual mammograms starting at starting at age 40age 40

Clinical breast examsClinical breast examsndash every year starting at age 40every year starting at age 40ndash every 3 years for women age every 3 years for women age 20-3920-39

Self-breast examsSelf-breast exams monthly starting monthly starting at age 20at age 20

Breast Self-Exam ndash Step Breast Self-Exam ndash Step 11 Begin by looking at your breasts in the mirror Begin by looking at your breasts in the mirror

with your shoulders straight and yourwith your shoulders straight and your

arms on your hipsarms on your hips Heres what you should look forHeres what you should look for

Breasts that are their usual size shape and colorBreasts that are their usual size shape and color

--Breasts that are evenly shaped without visible --Breasts that are evenly shaped without visible distortion or swellingdistortion or swelling

If you see any of the following changes bring If you see any of the following changes bring them to your doctors attentionthem to your doctors attention

--Dimpling puckering or bulging of the skin--Dimpling puckering or bulging of the skin

--A nipple that has changed position or become --A nipple that has changed position or become inverted (pushed inward instead ofinverted (pushed inward instead of

sticking out)sticking out) --Redness soreness rash or swelling--Redness soreness rash or swelling

Breast Self-Exam ndash Step Breast Self-Exam ndash Step 22

Raise your arms and look for the Raise your arms and look for the

samesame

changeschanges

Breast Self-Exam ndash Step Breast Self-Exam ndash Step 33 Feel your breasts while lying down using Feel your breasts while lying down using

your right hand to feel your left breast and your right hand to feel your left breast and then your left hand to feel your right breast then your left hand to feel your right breast Use a firm smooth touch with the first few Use a firm smooth touch with the first few fingers of your hand keeping the fingersfingers of your hand keeping the fingers

flat and togetherflat and together

Cover the entire breast from top to Cover the entire breast from top to bottom side to sidemdashfrom your bottom side to sidemdashfrom your collarbone to the top of your abdomen collarbone to the top of your abdomen and from your armpit to your cleavageand from your armpit to your cleavage

Breast Self-Exam ndash Step Breast Self-Exam ndash Step 44

Finally feel your breasts while you are Finally feel your breasts while you are standing or sitting Many women find standing or sitting Many women find that the easiest way to feel their breasts that the easiest way to feel their breasts is when their skin is wet and slippery is when their skin is wet and slippery so they like to do this step in the so they like to do this step in the shower Cover your entire breast using shower Cover your entire breast using the same hand movements described in the same hand movements described in Step 3Step 3

InvestigationsInvestigations

Mammography (conrsquot)Mammography (conrsquot) 1048698 1048698 Standard mammography Standard mammography depends on depends on

density of the tissue and its ability to stop density of the tissue and its ability to stop xrayxray

beam from exposing film placed on the other beam from exposing film placed on the other side of the breastside of the breast

Digital mammography Digital mammography works on the same works on the same principle but there is also some ability to principle but there is also some ability to manipulate the image by computer Main manipulate the image by computer Main advantage is storage of the filmsadvantage is storage of the films

UltrasoundUltrasound

Since solid tissue andSince solid tissue and collections of fluid look thecollections of fluid look the same on mammographysame on mammography ultrasound is very useful in ultrasound is very useful in telling whether a mass istelling whether a mass is solid or fluid and if solid ifsolid or fluid and if solid if characteristics arecharacteristics are suspicioussuspicious CystCyst

MRIMRI MRI relies on completely different type of MRI relies on completely different type of

wavewave

energy a strong magnet that affects the energy a strong magnet that affects the charge incharge in

the nuclei As magnetic force is applied and the nuclei As magnetic force is applied and thenthen

released different types of tissue send back released different types of tissue send back different types of radio wavesdifferent types of radio waves

MRI can be extremely useful in very denseMRI can be extremely useful in very dense

breasts hereditary casesbreasts hereditary cases

Fine needle aspiration of a palpable mass

1048698 Fine needle aspiration takes individual cells out ofmass Can be done for palpable or non-palpablemasses Does not show architecture especially wallof duct so best used to confirm strong suspicions

Fine Needle Aspiration

C0 No epithelial cellsC1 InadequateC2 BenignC3 AtypiaC4 SuspiciousC5 Malignant

1048698 Core biopsy can also bedone on palpable and non palpableabnormalities and on microcalcifications

Core Biopsy

B1 Normal tissue unsatisfactoryB2 BenignB3 Lesion uncertain malignant potentialB4 Suspicion of malignancyB5a In situ malignancyB5b Invasive malignancy

Investigations for Investigations for metastasismetastasis

1- abdominal ultrasound1- abdominal ultrasound

2- chest x ray or CT2- chest x ray or CT

3- bone survey or bone scan3- bone survey or bone scan

Established prognostic Established prognostic factorsfactors

bull Nodal status Nodal status bull Tumor size Tumor size bull Lymph node Lymph node bull Grade Grade bull ERPR StatusERPR Statusbull Age Age bull Lymphatic invasionLymphatic invasionbull Histological tumor typeHistological tumor type bull Perinodular infiltrationPerinodular infiltration

TREATMENT OPTIONS FOR PRIMARY OPERABLE BREAST CANCER Objective Options

Local control Lumpectomy Lumpectomy with breast irradiation Mastectomy

Regional control Axillary lymph node dissection Regional irradiation

Control of occult Chemotherapymicrometastatic disease Hormone therapy

Improved function and cosmesis Breast-conserving therapy Reconstruction (immediate or delayed)

Localized breast cancer Surgery is mainstay Halsted 1882 radical mastectomy

John Hopkins

Metastatic breast cancer Systemic treatment

Radical mastectomy A Entire breast and a

chest wall muscle is removed

LNs in the level 1 (B) and level 2 (C ) and even sometimes more distant lymph node groups (D E and F) were also removed

Modified radical mastectomy (MRM)

A Entire breast is removed

Classically some lymph nodes in the level 1 (B) and level 2 (C ) were removed called an axillary lymph node dissection

MRM = simple mastectomy + ALND

Breast conserving surgery

Also called lumpectomy with safety margin with axillary clearance or sentinel lymph node biopsy

RT should be followed

Adjuvant systemic treatment

Hypothesis Eradicate micrometastasis From effective treatment for overt

(macro) metastasis

Chemotherapy Hormone therapy

Adjuvant chemotherapy

CMF first generation 1970s Cyclophosphamide Methotrexate 5-FU

Benefit in Distant recurrence Survival

Adjuvant chemotherapy

CAF or CEF 2nd generation 1980s Cyclophophamide Adramycin(or Epirubicin) 5-FU

More toxic than CMF CAF better than CMF in high-risk group

Axilla LN+ LN- but tumor large or other risk factor

Adjuvant chemotherapy

Incorporate Taxane TAC 3rd generation mid-1990s

Taxotere Adriamycin Cyclophosphamide

More toxic than CAF Better than CAF in high-risk group

Need more time to observe

Adjuvant Herceptin(HER-2 (Human Epidermal growth factor Receptor 2) also

known as proto-oncogene Neu Over expression of this gene is correlated with higher aggressiveness in breast cancer

HER2 is a cell membrane surface-bound receptor tyrosine kinase and is normally involved in the signal transduction pathways leading to cell growth and differentiation)

Effective in Her2+ pts ICH3+ FISH+

Herceptin + adjuvant chemotherapy Optimal role to be defined

Concurrent or sequential Maintenance Duration

American Joint Committee on Cancer TNM Staging System for Breast American Joint Committee on Cancer TNM Staging System for Breast Cancer Cancer

Primary Tumor (T)Primary Tumor (T) TX Primary tumor cannot be assessedTX Primary tumor cannot be assessed T0 No evidence of primary tumorT0 No evidence of primary tumor Tis Carcinoma Tis Carcinoma in situin situ

Note Pagets disease associated with a tumor is classified according Note Pagets disease associated with a tumor is classified according to the size of the tumor to the size of the tumor

T1 Tumor 2 cm or less in greatest dimensionT1 Tumor 2 cm or less in greatest dimension

T1mic Microinvasion 01 cm or less in greatest dimensionT1mic Microinvasion 01 cm or less in greatest dimension

T1a Tumor more than 01 cm but not more than 05 cm in greatest T1a Tumor more than 01 cm but not more than 05 cm in greatest dimension dimension

T1b Tumor more than 05 cm but not more than 1 cm in greatest T1b Tumor more than 05 cm but not more than 1 cm in greatest dimension dimension

T1c Tumor more than 1 cm but not more than 2 cm in greatest T1c Tumor more than 1 cm but not more than 2 cm in greatest dimensiondimension

T2 Tumor more than 2 cm but not more than 5 cm in greatest T2 Tumor more than 2 cm but not more than 5 cm in greatest dimensiondimension

T3 Tumor more than 5 cm in greatest dimensionT3 Tumor more than 5 cm in greatest dimension T4a Extension to chest wall not including pectoralis muscleT4a Extension to chest wall not including pectoralis muscle

T4b Edema (including peau dorange) or ulceration of the skin of the T4b Edema (including peau dorange) or ulceration of the skin of the breast or satellite skin nodules confined to the same breast breast or satellite skin nodules confined to the same breast

T4c Both T4a and T4bT4c Both T4a and T4b

T4d Inflammatory carcinomaT4d Inflammatory carcinoma

Regional Lymph Nodes (N) Regional Lymph Nodes (N) NX Regional lymph nodes cannot be assessed (eg NX Regional lymph nodes cannot be assessed (eg

previously removed) previously removed) N0 No regional lymph node metastasisN0 No regional lymph node metastasis N1 Metastasis to movable ipsilateral axillary lymph N1 Metastasis to movable ipsilateral axillary lymph

node(s)node(s) N2 N2

N2a Metastases in ipsilateral axillary lymph nodes N2a Metastases in ipsilateral axillary lymph nodes fixed to one another (matted) or to other structures fixed to one another (matted) or to other structures

N2b Metastasis only in N2b Metastasis only in clinically apparentclinically apparent ipsilateral ipsilateral internal mammary nodes and in theinternal mammary nodes and in the absence absence of of clinically evident axillary lymph node metastasis clinically evident axillary lymph node metastasis

N3N3

N3a Metastasis in ipsilateral infraclavicular lymph N3a Metastasis in ipsilateral infraclavicular lymph node(s)node(s)

N3b Metastasis in ipsilateral internal mammary N3b Metastasis in ipsilateral internal mammary lymph node(s) and axillary lymph node(s) lymph node(s) and axillary lymph node(s)

N3c Metastasis in ipsilateral supraclavicular lymph N3c Metastasis in ipsilateral supraclavicular lymph node(s)node(s)

M ( METASTASIS)M ( METASTASIS)

MX metastasis can no be assessedMX metastasis can no be assessed

M0 no metastasisM0 no metastasis

M1 metastasisM1 metastasis

American Cancer SocietyAmerican Cancer SocietyScreening RecommendationsScreening Recommendations

Annual mammogramsAnnual mammograms starting at starting at age 40age 40

Clinical breast examsClinical breast examsndash every year starting at age 40every year starting at age 40ndash every 3 years for women age every 3 years for women age 20-3920-39

Self-breast examsSelf-breast exams monthly starting monthly starting at age 20at age 20

Breast Self-Exam ndash Step Breast Self-Exam ndash Step 11 Begin by looking at your breasts in the mirror Begin by looking at your breasts in the mirror

with your shoulders straight and yourwith your shoulders straight and your

arms on your hipsarms on your hips Heres what you should look forHeres what you should look for

Breasts that are their usual size shape and colorBreasts that are their usual size shape and color

--Breasts that are evenly shaped without visible --Breasts that are evenly shaped without visible distortion or swellingdistortion or swelling

If you see any of the following changes bring If you see any of the following changes bring them to your doctors attentionthem to your doctors attention

--Dimpling puckering or bulging of the skin--Dimpling puckering or bulging of the skin

--A nipple that has changed position or become --A nipple that has changed position or become inverted (pushed inward instead ofinverted (pushed inward instead of

sticking out)sticking out) --Redness soreness rash or swelling--Redness soreness rash or swelling

Breast Self-Exam ndash Step Breast Self-Exam ndash Step 22

Raise your arms and look for the Raise your arms and look for the

samesame

changeschanges

Breast Self-Exam ndash Step Breast Self-Exam ndash Step 33 Feel your breasts while lying down using Feel your breasts while lying down using

your right hand to feel your left breast and your right hand to feel your left breast and then your left hand to feel your right breast then your left hand to feel your right breast Use a firm smooth touch with the first few Use a firm smooth touch with the first few fingers of your hand keeping the fingersfingers of your hand keeping the fingers

flat and togetherflat and together

Cover the entire breast from top to Cover the entire breast from top to bottom side to sidemdashfrom your bottom side to sidemdashfrom your collarbone to the top of your abdomen collarbone to the top of your abdomen and from your armpit to your cleavageand from your armpit to your cleavage

Breast Self-Exam ndash Step Breast Self-Exam ndash Step 44

Finally feel your breasts while you are Finally feel your breasts while you are standing or sitting Many women find standing or sitting Many women find that the easiest way to feel their breasts that the easiest way to feel their breasts is when their skin is wet and slippery is when their skin is wet and slippery so they like to do this step in the so they like to do this step in the shower Cover your entire breast using shower Cover your entire breast using the same hand movements described in the same hand movements described in Step 3Step 3

InvestigationsInvestigations

Mammography (conrsquot)Mammography (conrsquot) 1048698 1048698 Standard mammography Standard mammography depends on depends on

density of the tissue and its ability to stop density of the tissue and its ability to stop xrayxray

beam from exposing film placed on the other beam from exposing film placed on the other side of the breastside of the breast

Digital mammography Digital mammography works on the same works on the same principle but there is also some ability to principle but there is also some ability to manipulate the image by computer Main manipulate the image by computer Main advantage is storage of the filmsadvantage is storage of the films

UltrasoundUltrasound

Since solid tissue andSince solid tissue and collections of fluid look thecollections of fluid look the same on mammographysame on mammography ultrasound is very useful in ultrasound is very useful in telling whether a mass istelling whether a mass is solid or fluid and if solid ifsolid or fluid and if solid if characteristics arecharacteristics are suspicioussuspicious CystCyst

MRIMRI MRI relies on completely different type of MRI relies on completely different type of

wavewave

energy a strong magnet that affects the energy a strong magnet that affects the charge incharge in

the nuclei As magnetic force is applied and the nuclei As magnetic force is applied and thenthen

released different types of tissue send back released different types of tissue send back different types of radio wavesdifferent types of radio waves

MRI can be extremely useful in very denseMRI can be extremely useful in very dense

breasts hereditary casesbreasts hereditary cases

Fine needle aspiration of a palpable mass

1048698 Fine needle aspiration takes individual cells out ofmass Can be done for palpable or non-palpablemasses Does not show architecture especially wallof duct so best used to confirm strong suspicions

Fine Needle Aspiration

C0 No epithelial cellsC1 InadequateC2 BenignC3 AtypiaC4 SuspiciousC5 Malignant

1048698 Core biopsy can also bedone on palpable and non palpableabnormalities and on microcalcifications

Core Biopsy

B1 Normal tissue unsatisfactoryB2 BenignB3 Lesion uncertain malignant potentialB4 Suspicion of malignancyB5a In situ malignancyB5b Invasive malignancy

Investigations for Investigations for metastasismetastasis

1- abdominal ultrasound1- abdominal ultrasound

2- chest x ray or CT2- chest x ray or CT

3- bone survey or bone scan3- bone survey or bone scan

Established prognostic Established prognostic factorsfactors

bull Nodal status Nodal status bull Tumor size Tumor size bull Lymph node Lymph node bull Grade Grade bull ERPR StatusERPR Statusbull Age Age bull Lymphatic invasionLymphatic invasionbull Histological tumor typeHistological tumor type bull Perinodular infiltrationPerinodular infiltration

TREATMENT OPTIONS FOR PRIMARY OPERABLE BREAST CANCER Objective Options

Local control Lumpectomy Lumpectomy with breast irradiation Mastectomy

Regional control Axillary lymph node dissection Regional irradiation

Control of occult Chemotherapymicrometastatic disease Hormone therapy

Improved function and cosmesis Breast-conserving therapy Reconstruction (immediate or delayed)

Localized breast cancer Surgery is mainstay Halsted 1882 radical mastectomy

John Hopkins

Metastatic breast cancer Systemic treatment

Radical mastectomy A Entire breast and a

chest wall muscle is removed

LNs in the level 1 (B) and level 2 (C ) and even sometimes more distant lymph node groups (D E and F) were also removed

Modified radical mastectomy (MRM)

A Entire breast is removed

Classically some lymph nodes in the level 1 (B) and level 2 (C ) were removed called an axillary lymph node dissection

MRM = simple mastectomy + ALND

Breast conserving surgery

Also called lumpectomy with safety margin with axillary clearance or sentinel lymph node biopsy

RT should be followed

Adjuvant systemic treatment

Hypothesis Eradicate micrometastasis From effective treatment for overt

(macro) metastasis

Chemotherapy Hormone therapy

Adjuvant chemotherapy

CMF first generation 1970s Cyclophosphamide Methotrexate 5-FU

Benefit in Distant recurrence Survival

Adjuvant chemotherapy

CAF or CEF 2nd generation 1980s Cyclophophamide Adramycin(or Epirubicin) 5-FU

More toxic than CMF CAF better than CMF in high-risk group

Axilla LN+ LN- but tumor large or other risk factor

Adjuvant chemotherapy

Incorporate Taxane TAC 3rd generation mid-1990s

Taxotere Adriamycin Cyclophosphamide

More toxic than CAF Better than CAF in high-risk group

Need more time to observe

Adjuvant Herceptin(HER-2 (Human Epidermal growth factor Receptor 2) also

known as proto-oncogene Neu Over expression of this gene is correlated with higher aggressiveness in breast cancer

HER2 is a cell membrane surface-bound receptor tyrosine kinase and is normally involved in the signal transduction pathways leading to cell growth and differentiation)

Effective in Her2+ pts ICH3+ FISH+

Herceptin + adjuvant chemotherapy Optimal role to be defined

Concurrent or sequential Maintenance Duration

Regional Lymph Nodes (N) Regional Lymph Nodes (N) NX Regional lymph nodes cannot be assessed (eg NX Regional lymph nodes cannot be assessed (eg

previously removed) previously removed) N0 No regional lymph node metastasisN0 No regional lymph node metastasis N1 Metastasis to movable ipsilateral axillary lymph N1 Metastasis to movable ipsilateral axillary lymph

node(s)node(s) N2 N2

N2a Metastases in ipsilateral axillary lymph nodes N2a Metastases in ipsilateral axillary lymph nodes fixed to one another (matted) or to other structures fixed to one another (matted) or to other structures

N2b Metastasis only in N2b Metastasis only in clinically apparentclinically apparent ipsilateral ipsilateral internal mammary nodes and in theinternal mammary nodes and in the absence absence of of clinically evident axillary lymph node metastasis clinically evident axillary lymph node metastasis

N3N3

N3a Metastasis in ipsilateral infraclavicular lymph N3a Metastasis in ipsilateral infraclavicular lymph node(s)node(s)

N3b Metastasis in ipsilateral internal mammary N3b Metastasis in ipsilateral internal mammary lymph node(s) and axillary lymph node(s) lymph node(s) and axillary lymph node(s)

N3c Metastasis in ipsilateral supraclavicular lymph N3c Metastasis in ipsilateral supraclavicular lymph node(s)node(s)

M ( METASTASIS)M ( METASTASIS)

MX metastasis can no be assessedMX metastasis can no be assessed

M0 no metastasisM0 no metastasis

M1 metastasisM1 metastasis

American Cancer SocietyAmerican Cancer SocietyScreening RecommendationsScreening Recommendations

Annual mammogramsAnnual mammograms starting at starting at age 40age 40

Clinical breast examsClinical breast examsndash every year starting at age 40every year starting at age 40ndash every 3 years for women age every 3 years for women age 20-3920-39

Self-breast examsSelf-breast exams monthly starting monthly starting at age 20at age 20

Breast Self-Exam ndash Step Breast Self-Exam ndash Step 11 Begin by looking at your breasts in the mirror Begin by looking at your breasts in the mirror

with your shoulders straight and yourwith your shoulders straight and your

arms on your hipsarms on your hips Heres what you should look forHeres what you should look for

Breasts that are their usual size shape and colorBreasts that are their usual size shape and color

--Breasts that are evenly shaped without visible --Breasts that are evenly shaped without visible distortion or swellingdistortion or swelling

If you see any of the following changes bring If you see any of the following changes bring them to your doctors attentionthem to your doctors attention

--Dimpling puckering or bulging of the skin--Dimpling puckering or bulging of the skin

--A nipple that has changed position or become --A nipple that has changed position or become inverted (pushed inward instead ofinverted (pushed inward instead of

sticking out)sticking out) --Redness soreness rash or swelling--Redness soreness rash or swelling

Breast Self-Exam ndash Step Breast Self-Exam ndash Step 22

Raise your arms and look for the Raise your arms and look for the

samesame

changeschanges

Breast Self-Exam ndash Step Breast Self-Exam ndash Step 33 Feel your breasts while lying down using Feel your breasts while lying down using

your right hand to feel your left breast and your right hand to feel your left breast and then your left hand to feel your right breast then your left hand to feel your right breast Use a firm smooth touch with the first few Use a firm smooth touch with the first few fingers of your hand keeping the fingersfingers of your hand keeping the fingers

flat and togetherflat and together

Cover the entire breast from top to Cover the entire breast from top to bottom side to sidemdashfrom your bottom side to sidemdashfrom your collarbone to the top of your abdomen collarbone to the top of your abdomen and from your armpit to your cleavageand from your armpit to your cleavage

Breast Self-Exam ndash Step Breast Self-Exam ndash Step 44

Finally feel your breasts while you are Finally feel your breasts while you are standing or sitting Many women find standing or sitting Many women find that the easiest way to feel their breasts that the easiest way to feel their breasts is when their skin is wet and slippery is when their skin is wet and slippery so they like to do this step in the so they like to do this step in the shower Cover your entire breast using shower Cover your entire breast using the same hand movements described in the same hand movements described in Step 3Step 3

InvestigationsInvestigations

Mammography (conrsquot)Mammography (conrsquot) 1048698 1048698 Standard mammography Standard mammography depends on depends on

density of the tissue and its ability to stop density of the tissue and its ability to stop xrayxray

beam from exposing film placed on the other beam from exposing film placed on the other side of the breastside of the breast

Digital mammography Digital mammography works on the same works on the same principle but there is also some ability to principle but there is also some ability to manipulate the image by computer Main manipulate the image by computer Main advantage is storage of the filmsadvantage is storage of the films

UltrasoundUltrasound

Since solid tissue andSince solid tissue and collections of fluid look thecollections of fluid look the same on mammographysame on mammography ultrasound is very useful in ultrasound is very useful in telling whether a mass istelling whether a mass is solid or fluid and if solid ifsolid or fluid and if solid if characteristics arecharacteristics are suspicioussuspicious CystCyst

MRIMRI MRI relies on completely different type of MRI relies on completely different type of

wavewave

energy a strong magnet that affects the energy a strong magnet that affects the charge incharge in

the nuclei As magnetic force is applied and the nuclei As magnetic force is applied and thenthen

released different types of tissue send back released different types of tissue send back different types of radio wavesdifferent types of radio waves

MRI can be extremely useful in very denseMRI can be extremely useful in very dense

breasts hereditary casesbreasts hereditary cases

Fine needle aspiration of a palpable mass

1048698 Fine needle aspiration takes individual cells out ofmass Can be done for palpable or non-palpablemasses Does not show architecture especially wallof duct so best used to confirm strong suspicions

Fine Needle Aspiration

C0 No epithelial cellsC1 InadequateC2 BenignC3 AtypiaC4 SuspiciousC5 Malignant

1048698 Core biopsy can also bedone on palpable and non palpableabnormalities and on microcalcifications

Core Biopsy

B1 Normal tissue unsatisfactoryB2 BenignB3 Lesion uncertain malignant potentialB4 Suspicion of malignancyB5a In situ malignancyB5b Invasive malignancy

Investigations for Investigations for metastasismetastasis

1- abdominal ultrasound1- abdominal ultrasound

2- chest x ray or CT2- chest x ray or CT

3- bone survey or bone scan3- bone survey or bone scan

Established prognostic Established prognostic factorsfactors

bull Nodal status Nodal status bull Tumor size Tumor size bull Lymph node Lymph node bull Grade Grade bull ERPR StatusERPR Statusbull Age Age bull Lymphatic invasionLymphatic invasionbull Histological tumor typeHistological tumor type bull Perinodular infiltrationPerinodular infiltration

TREATMENT OPTIONS FOR PRIMARY OPERABLE BREAST CANCER Objective Options

Local control Lumpectomy Lumpectomy with breast irradiation Mastectomy

Regional control Axillary lymph node dissection Regional irradiation

Control of occult Chemotherapymicrometastatic disease Hormone therapy

Improved function and cosmesis Breast-conserving therapy Reconstruction (immediate or delayed)

Localized breast cancer Surgery is mainstay Halsted 1882 radical mastectomy

John Hopkins

Metastatic breast cancer Systemic treatment

Radical mastectomy A Entire breast and a

chest wall muscle is removed

LNs in the level 1 (B) and level 2 (C ) and even sometimes more distant lymph node groups (D E and F) were also removed

Modified radical mastectomy (MRM)

A Entire breast is removed

Classically some lymph nodes in the level 1 (B) and level 2 (C ) were removed called an axillary lymph node dissection

MRM = simple mastectomy + ALND

Breast conserving surgery

Also called lumpectomy with safety margin with axillary clearance or sentinel lymph node biopsy

RT should be followed

Adjuvant systemic treatment

Hypothesis Eradicate micrometastasis From effective treatment for overt

(macro) metastasis

Chemotherapy Hormone therapy

Adjuvant chemotherapy

CMF first generation 1970s Cyclophosphamide Methotrexate 5-FU

Benefit in Distant recurrence Survival

Adjuvant chemotherapy

CAF or CEF 2nd generation 1980s Cyclophophamide Adramycin(or Epirubicin) 5-FU

More toxic than CMF CAF better than CMF in high-risk group

Axilla LN+ LN- but tumor large or other risk factor

Adjuvant chemotherapy

Incorporate Taxane TAC 3rd generation mid-1990s

Taxotere Adriamycin Cyclophosphamide

More toxic than CAF Better than CAF in high-risk group

Need more time to observe

Adjuvant Herceptin(HER-2 (Human Epidermal growth factor Receptor 2) also

known as proto-oncogene Neu Over expression of this gene is correlated with higher aggressiveness in breast cancer

HER2 is a cell membrane surface-bound receptor tyrosine kinase and is normally involved in the signal transduction pathways leading to cell growth and differentiation)

Effective in Her2+ pts ICH3+ FISH+

Herceptin + adjuvant chemotherapy Optimal role to be defined

Concurrent or sequential Maintenance Duration

M ( METASTASIS)M ( METASTASIS)

MX metastasis can no be assessedMX metastasis can no be assessed

M0 no metastasisM0 no metastasis

M1 metastasisM1 metastasis

American Cancer SocietyAmerican Cancer SocietyScreening RecommendationsScreening Recommendations

Annual mammogramsAnnual mammograms starting at starting at age 40age 40

Clinical breast examsClinical breast examsndash every year starting at age 40every year starting at age 40ndash every 3 years for women age every 3 years for women age 20-3920-39

Self-breast examsSelf-breast exams monthly starting monthly starting at age 20at age 20

Breast Self-Exam ndash Step Breast Self-Exam ndash Step 11 Begin by looking at your breasts in the mirror Begin by looking at your breasts in the mirror

with your shoulders straight and yourwith your shoulders straight and your

arms on your hipsarms on your hips Heres what you should look forHeres what you should look for

Breasts that are their usual size shape and colorBreasts that are their usual size shape and color

--Breasts that are evenly shaped without visible --Breasts that are evenly shaped without visible distortion or swellingdistortion or swelling

If you see any of the following changes bring If you see any of the following changes bring them to your doctors attentionthem to your doctors attention

--Dimpling puckering or bulging of the skin--Dimpling puckering or bulging of the skin

--A nipple that has changed position or become --A nipple that has changed position or become inverted (pushed inward instead ofinverted (pushed inward instead of

sticking out)sticking out) --Redness soreness rash or swelling--Redness soreness rash or swelling

Breast Self-Exam ndash Step Breast Self-Exam ndash Step 22

Raise your arms and look for the Raise your arms and look for the

samesame

changeschanges

Breast Self-Exam ndash Step Breast Self-Exam ndash Step 33 Feel your breasts while lying down using Feel your breasts while lying down using

your right hand to feel your left breast and your right hand to feel your left breast and then your left hand to feel your right breast then your left hand to feel your right breast Use a firm smooth touch with the first few Use a firm smooth touch with the first few fingers of your hand keeping the fingersfingers of your hand keeping the fingers

flat and togetherflat and together

Cover the entire breast from top to Cover the entire breast from top to bottom side to sidemdashfrom your bottom side to sidemdashfrom your collarbone to the top of your abdomen collarbone to the top of your abdomen and from your armpit to your cleavageand from your armpit to your cleavage

Breast Self-Exam ndash Step Breast Self-Exam ndash Step 44

Finally feel your breasts while you are Finally feel your breasts while you are standing or sitting Many women find standing or sitting Many women find that the easiest way to feel their breasts that the easiest way to feel their breasts is when their skin is wet and slippery is when their skin is wet and slippery so they like to do this step in the so they like to do this step in the shower Cover your entire breast using shower Cover your entire breast using the same hand movements described in the same hand movements described in Step 3Step 3

InvestigationsInvestigations

Mammography (conrsquot)Mammography (conrsquot) 1048698 1048698 Standard mammography Standard mammography depends on depends on

density of the tissue and its ability to stop density of the tissue and its ability to stop xrayxray

beam from exposing film placed on the other beam from exposing film placed on the other side of the breastside of the breast

Digital mammography Digital mammography works on the same works on the same principle but there is also some ability to principle but there is also some ability to manipulate the image by computer Main manipulate the image by computer Main advantage is storage of the filmsadvantage is storage of the films

UltrasoundUltrasound

Since solid tissue andSince solid tissue and collections of fluid look thecollections of fluid look the same on mammographysame on mammography ultrasound is very useful in ultrasound is very useful in telling whether a mass istelling whether a mass is solid or fluid and if solid ifsolid or fluid and if solid if characteristics arecharacteristics are suspicioussuspicious CystCyst

MRIMRI MRI relies on completely different type of MRI relies on completely different type of

wavewave

energy a strong magnet that affects the energy a strong magnet that affects the charge incharge in

the nuclei As magnetic force is applied and the nuclei As magnetic force is applied and thenthen

released different types of tissue send back released different types of tissue send back different types of radio wavesdifferent types of radio waves

MRI can be extremely useful in very denseMRI can be extremely useful in very dense

breasts hereditary casesbreasts hereditary cases

Fine needle aspiration of a palpable mass

1048698 Fine needle aspiration takes individual cells out ofmass Can be done for palpable or non-palpablemasses Does not show architecture especially wallof duct so best used to confirm strong suspicions

Fine Needle Aspiration

C0 No epithelial cellsC1 InadequateC2 BenignC3 AtypiaC4 SuspiciousC5 Malignant

1048698 Core biopsy can also bedone on palpable and non palpableabnormalities and on microcalcifications

Core Biopsy

B1 Normal tissue unsatisfactoryB2 BenignB3 Lesion uncertain malignant potentialB4 Suspicion of malignancyB5a In situ malignancyB5b Invasive malignancy

Investigations for Investigations for metastasismetastasis

1- abdominal ultrasound1- abdominal ultrasound

2- chest x ray or CT2- chest x ray or CT

3- bone survey or bone scan3- bone survey or bone scan

Established prognostic Established prognostic factorsfactors

bull Nodal status Nodal status bull Tumor size Tumor size bull Lymph node Lymph node bull Grade Grade bull ERPR StatusERPR Statusbull Age Age bull Lymphatic invasionLymphatic invasionbull Histological tumor typeHistological tumor type bull Perinodular infiltrationPerinodular infiltration

TREATMENT OPTIONS FOR PRIMARY OPERABLE BREAST CANCER Objective Options

Local control Lumpectomy Lumpectomy with breast irradiation Mastectomy

Regional control Axillary lymph node dissection Regional irradiation

Control of occult Chemotherapymicrometastatic disease Hormone therapy

Improved function and cosmesis Breast-conserving therapy Reconstruction (immediate or delayed)

Localized breast cancer Surgery is mainstay Halsted 1882 radical mastectomy

John Hopkins

Metastatic breast cancer Systemic treatment

Radical mastectomy A Entire breast and a

chest wall muscle is removed

LNs in the level 1 (B) and level 2 (C ) and even sometimes more distant lymph node groups (D E and F) were also removed

Modified radical mastectomy (MRM)

A Entire breast is removed

Classically some lymph nodes in the level 1 (B) and level 2 (C ) were removed called an axillary lymph node dissection

MRM = simple mastectomy + ALND

Breast conserving surgery

Also called lumpectomy with safety margin with axillary clearance or sentinel lymph node biopsy

RT should be followed

Adjuvant systemic treatment

Hypothesis Eradicate micrometastasis From effective treatment for overt

(macro) metastasis

Chemotherapy Hormone therapy

Adjuvant chemotherapy

CMF first generation 1970s Cyclophosphamide Methotrexate 5-FU

Benefit in Distant recurrence Survival

Adjuvant chemotherapy

CAF or CEF 2nd generation 1980s Cyclophophamide Adramycin(or Epirubicin) 5-FU

More toxic than CMF CAF better than CMF in high-risk group

Axilla LN+ LN- but tumor large or other risk factor

Adjuvant chemotherapy

Incorporate Taxane TAC 3rd generation mid-1990s

Taxotere Adriamycin Cyclophosphamide

More toxic than CAF Better than CAF in high-risk group

Need more time to observe

Adjuvant Herceptin(HER-2 (Human Epidermal growth factor Receptor 2) also

known as proto-oncogene Neu Over expression of this gene is correlated with higher aggressiveness in breast cancer

HER2 is a cell membrane surface-bound receptor tyrosine kinase and is normally involved in the signal transduction pathways leading to cell growth and differentiation)

Effective in Her2+ pts ICH3+ FISH+

Herceptin + adjuvant chemotherapy Optimal role to be defined

Concurrent or sequential Maintenance Duration

American Cancer SocietyAmerican Cancer SocietyScreening RecommendationsScreening Recommendations

Annual mammogramsAnnual mammograms starting at starting at age 40age 40

Clinical breast examsClinical breast examsndash every year starting at age 40every year starting at age 40ndash every 3 years for women age every 3 years for women age 20-3920-39

Self-breast examsSelf-breast exams monthly starting monthly starting at age 20at age 20

Breast Self-Exam ndash Step Breast Self-Exam ndash Step 11 Begin by looking at your breasts in the mirror Begin by looking at your breasts in the mirror

with your shoulders straight and yourwith your shoulders straight and your

arms on your hipsarms on your hips Heres what you should look forHeres what you should look for

Breasts that are their usual size shape and colorBreasts that are their usual size shape and color

--Breasts that are evenly shaped without visible --Breasts that are evenly shaped without visible distortion or swellingdistortion or swelling

If you see any of the following changes bring If you see any of the following changes bring them to your doctors attentionthem to your doctors attention

--Dimpling puckering or bulging of the skin--Dimpling puckering or bulging of the skin

--A nipple that has changed position or become --A nipple that has changed position or become inverted (pushed inward instead ofinverted (pushed inward instead of

sticking out)sticking out) --Redness soreness rash or swelling--Redness soreness rash or swelling

Breast Self-Exam ndash Step Breast Self-Exam ndash Step 22

Raise your arms and look for the Raise your arms and look for the

samesame

changeschanges

Breast Self-Exam ndash Step Breast Self-Exam ndash Step 33 Feel your breasts while lying down using Feel your breasts while lying down using

your right hand to feel your left breast and your right hand to feel your left breast and then your left hand to feel your right breast then your left hand to feel your right breast Use a firm smooth touch with the first few Use a firm smooth touch with the first few fingers of your hand keeping the fingersfingers of your hand keeping the fingers

flat and togetherflat and together

Cover the entire breast from top to Cover the entire breast from top to bottom side to sidemdashfrom your bottom side to sidemdashfrom your collarbone to the top of your abdomen collarbone to the top of your abdomen and from your armpit to your cleavageand from your armpit to your cleavage

Breast Self-Exam ndash Step Breast Self-Exam ndash Step 44

Finally feel your breasts while you are Finally feel your breasts while you are standing or sitting Many women find standing or sitting Many women find that the easiest way to feel their breasts that the easiest way to feel their breasts is when their skin is wet and slippery is when their skin is wet and slippery so they like to do this step in the so they like to do this step in the shower Cover your entire breast using shower Cover your entire breast using the same hand movements described in the same hand movements described in Step 3Step 3

InvestigationsInvestigations

Mammography (conrsquot)Mammography (conrsquot) 1048698 1048698 Standard mammography Standard mammography depends on depends on

density of the tissue and its ability to stop density of the tissue and its ability to stop xrayxray

beam from exposing film placed on the other beam from exposing film placed on the other side of the breastside of the breast

Digital mammography Digital mammography works on the same works on the same principle but there is also some ability to principle but there is also some ability to manipulate the image by computer Main manipulate the image by computer Main advantage is storage of the filmsadvantage is storage of the films

UltrasoundUltrasound

Since solid tissue andSince solid tissue and collections of fluid look thecollections of fluid look the same on mammographysame on mammography ultrasound is very useful in ultrasound is very useful in telling whether a mass istelling whether a mass is solid or fluid and if solid ifsolid or fluid and if solid if characteristics arecharacteristics are suspicioussuspicious CystCyst

MRIMRI MRI relies on completely different type of MRI relies on completely different type of

wavewave

energy a strong magnet that affects the energy a strong magnet that affects the charge incharge in

the nuclei As magnetic force is applied and the nuclei As magnetic force is applied and thenthen

released different types of tissue send back released different types of tissue send back different types of radio wavesdifferent types of radio waves

MRI can be extremely useful in very denseMRI can be extremely useful in very dense

breasts hereditary casesbreasts hereditary cases

Fine needle aspiration of a palpable mass

1048698 Fine needle aspiration takes individual cells out ofmass Can be done for palpable or non-palpablemasses Does not show architecture especially wallof duct so best used to confirm strong suspicions

Fine Needle Aspiration

C0 No epithelial cellsC1 InadequateC2 BenignC3 AtypiaC4 SuspiciousC5 Malignant

1048698 Core biopsy can also bedone on palpable and non palpableabnormalities and on microcalcifications

Core Biopsy

B1 Normal tissue unsatisfactoryB2 BenignB3 Lesion uncertain malignant potentialB4 Suspicion of malignancyB5a In situ malignancyB5b Invasive malignancy

Investigations for Investigations for metastasismetastasis

1- abdominal ultrasound1- abdominal ultrasound

2- chest x ray or CT2- chest x ray or CT

3- bone survey or bone scan3- bone survey or bone scan

Established prognostic Established prognostic factorsfactors

bull Nodal status Nodal status bull Tumor size Tumor size bull Lymph node Lymph node bull Grade Grade bull ERPR StatusERPR Statusbull Age Age bull Lymphatic invasionLymphatic invasionbull Histological tumor typeHistological tumor type bull Perinodular infiltrationPerinodular infiltration

TREATMENT OPTIONS FOR PRIMARY OPERABLE BREAST CANCER Objective Options

Local control Lumpectomy Lumpectomy with breast irradiation Mastectomy

Regional control Axillary lymph node dissection Regional irradiation

Control of occult Chemotherapymicrometastatic disease Hormone therapy

Improved function and cosmesis Breast-conserving therapy Reconstruction (immediate or delayed)

Localized breast cancer Surgery is mainstay Halsted 1882 radical mastectomy

John Hopkins

Metastatic breast cancer Systemic treatment

Radical mastectomy A Entire breast and a

chest wall muscle is removed

LNs in the level 1 (B) and level 2 (C ) and even sometimes more distant lymph node groups (D E and F) were also removed

Modified radical mastectomy (MRM)

A Entire breast is removed

Classically some lymph nodes in the level 1 (B) and level 2 (C ) were removed called an axillary lymph node dissection

MRM = simple mastectomy + ALND

Breast conserving surgery

Also called lumpectomy with safety margin with axillary clearance or sentinel lymph node biopsy

RT should be followed

Adjuvant systemic treatment

Hypothesis Eradicate micrometastasis From effective treatment for overt

(macro) metastasis

Chemotherapy Hormone therapy

Adjuvant chemotherapy

CMF first generation 1970s Cyclophosphamide Methotrexate 5-FU

Benefit in Distant recurrence Survival

Adjuvant chemotherapy

CAF or CEF 2nd generation 1980s Cyclophophamide Adramycin(or Epirubicin) 5-FU

More toxic than CMF CAF better than CMF in high-risk group

Axilla LN+ LN- but tumor large or other risk factor

Adjuvant chemotherapy

Incorporate Taxane TAC 3rd generation mid-1990s

Taxotere Adriamycin Cyclophosphamide

More toxic than CAF Better than CAF in high-risk group

Need more time to observe

Adjuvant Herceptin(HER-2 (Human Epidermal growth factor Receptor 2) also

known as proto-oncogene Neu Over expression of this gene is correlated with higher aggressiveness in breast cancer

HER2 is a cell membrane surface-bound receptor tyrosine kinase and is normally involved in the signal transduction pathways leading to cell growth and differentiation)

Effective in Her2+ pts ICH3+ FISH+

Herceptin + adjuvant chemotherapy Optimal role to be defined

Concurrent or sequential Maintenance Duration

Breast Self-Exam ndash Step Breast Self-Exam ndash Step 11 Begin by looking at your breasts in the mirror Begin by looking at your breasts in the mirror

with your shoulders straight and yourwith your shoulders straight and your

arms on your hipsarms on your hips Heres what you should look forHeres what you should look for

Breasts that are their usual size shape and colorBreasts that are their usual size shape and color

--Breasts that are evenly shaped without visible --Breasts that are evenly shaped without visible distortion or swellingdistortion or swelling

If you see any of the following changes bring If you see any of the following changes bring them to your doctors attentionthem to your doctors attention

--Dimpling puckering or bulging of the skin--Dimpling puckering or bulging of the skin

--A nipple that has changed position or become --A nipple that has changed position or become inverted (pushed inward instead ofinverted (pushed inward instead of

sticking out)sticking out) --Redness soreness rash or swelling--Redness soreness rash or swelling

Breast Self-Exam ndash Step Breast Self-Exam ndash Step 22

Raise your arms and look for the Raise your arms and look for the

samesame

changeschanges

Breast Self-Exam ndash Step Breast Self-Exam ndash Step 33 Feel your breasts while lying down using Feel your breasts while lying down using

your right hand to feel your left breast and your right hand to feel your left breast and then your left hand to feel your right breast then your left hand to feel your right breast Use a firm smooth touch with the first few Use a firm smooth touch with the first few fingers of your hand keeping the fingersfingers of your hand keeping the fingers

flat and togetherflat and together

Cover the entire breast from top to Cover the entire breast from top to bottom side to sidemdashfrom your bottom side to sidemdashfrom your collarbone to the top of your abdomen collarbone to the top of your abdomen and from your armpit to your cleavageand from your armpit to your cleavage

Breast Self-Exam ndash Step Breast Self-Exam ndash Step 44

Finally feel your breasts while you are Finally feel your breasts while you are standing or sitting Many women find standing or sitting Many women find that the easiest way to feel their breasts that the easiest way to feel their breasts is when their skin is wet and slippery is when their skin is wet and slippery so they like to do this step in the so they like to do this step in the shower Cover your entire breast using shower Cover your entire breast using the same hand movements described in the same hand movements described in Step 3Step 3

InvestigationsInvestigations

Mammography (conrsquot)Mammography (conrsquot) 1048698 1048698 Standard mammography Standard mammography depends on depends on

density of the tissue and its ability to stop density of the tissue and its ability to stop xrayxray

beam from exposing film placed on the other beam from exposing film placed on the other side of the breastside of the breast

Digital mammography Digital mammography works on the same works on the same principle but there is also some ability to principle but there is also some ability to manipulate the image by computer Main manipulate the image by computer Main advantage is storage of the filmsadvantage is storage of the films

UltrasoundUltrasound

Since solid tissue andSince solid tissue and collections of fluid look thecollections of fluid look the same on mammographysame on mammography ultrasound is very useful in ultrasound is very useful in telling whether a mass istelling whether a mass is solid or fluid and if solid ifsolid or fluid and if solid if characteristics arecharacteristics are suspicioussuspicious CystCyst

MRIMRI MRI relies on completely different type of MRI relies on completely different type of

wavewave

energy a strong magnet that affects the energy a strong magnet that affects the charge incharge in

the nuclei As magnetic force is applied and the nuclei As magnetic force is applied and thenthen

released different types of tissue send back released different types of tissue send back different types of radio wavesdifferent types of radio waves

MRI can be extremely useful in very denseMRI can be extremely useful in very dense

breasts hereditary casesbreasts hereditary cases

Fine needle aspiration of a palpable mass

1048698 Fine needle aspiration takes individual cells out ofmass Can be done for palpable or non-palpablemasses Does not show architecture especially wallof duct so best used to confirm strong suspicions

Fine Needle Aspiration

C0 No epithelial cellsC1 InadequateC2 BenignC3 AtypiaC4 SuspiciousC5 Malignant

1048698 Core biopsy can also bedone on palpable and non palpableabnormalities and on microcalcifications

Core Biopsy

B1 Normal tissue unsatisfactoryB2 BenignB3 Lesion uncertain malignant potentialB4 Suspicion of malignancyB5a In situ malignancyB5b Invasive malignancy

Investigations for Investigations for metastasismetastasis

1- abdominal ultrasound1- abdominal ultrasound

2- chest x ray or CT2- chest x ray or CT

3- bone survey or bone scan3- bone survey or bone scan

Established prognostic Established prognostic factorsfactors

bull Nodal status Nodal status bull Tumor size Tumor size bull Lymph node Lymph node bull Grade Grade bull ERPR StatusERPR Statusbull Age Age bull Lymphatic invasionLymphatic invasionbull Histological tumor typeHistological tumor type bull Perinodular infiltrationPerinodular infiltration

TREATMENT OPTIONS FOR PRIMARY OPERABLE BREAST CANCER Objective Options

Local control Lumpectomy Lumpectomy with breast irradiation Mastectomy

Regional control Axillary lymph node dissection Regional irradiation

Control of occult Chemotherapymicrometastatic disease Hormone therapy

Improved function and cosmesis Breast-conserving therapy Reconstruction (immediate or delayed)

Localized breast cancer Surgery is mainstay Halsted 1882 radical mastectomy

John Hopkins

Metastatic breast cancer Systemic treatment

Radical mastectomy A Entire breast and a

chest wall muscle is removed

LNs in the level 1 (B) and level 2 (C ) and even sometimes more distant lymph node groups (D E and F) were also removed

Modified radical mastectomy (MRM)

A Entire breast is removed

Classically some lymph nodes in the level 1 (B) and level 2 (C ) were removed called an axillary lymph node dissection

MRM = simple mastectomy + ALND

Breast conserving surgery

Also called lumpectomy with safety margin with axillary clearance or sentinel lymph node biopsy

RT should be followed

Adjuvant systemic treatment

Hypothesis Eradicate micrometastasis From effective treatment for overt

(macro) metastasis

Chemotherapy Hormone therapy

Adjuvant chemotherapy

CMF first generation 1970s Cyclophosphamide Methotrexate 5-FU

Benefit in Distant recurrence Survival

Adjuvant chemotherapy

CAF or CEF 2nd generation 1980s Cyclophophamide Adramycin(or Epirubicin) 5-FU

More toxic than CMF CAF better than CMF in high-risk group

Axilla LN+ LN- but tumor large or other risk factor

Adjuvant chemotherapy

Incorporate Taxane TAC 3rd generation mid-1990s

Taxotere Adriamycin Cyclophosphamide

More toxic than CAF Better than CAF in high-risk group

Need more time to observe

Adjuvant Herceptin(HER-2 (Human Epidermal growth factor Receptor 2) also

known as proto-oncogene Neu Over expression of this gene is correlated with higher aggressiveness in breast cancer

HER2 is a cell membrane surface-bound receptor tyrosine kinase and is normally involved in the signal transduction pathways leading to cell growth and differentiation)

Effective in Her2+ pts ICH3+ FISH+

Herceptin + adjuvant chemotherapy Optimal role to be defined

Concurrent or sequential Maintenance Duration

Breast Self-Exam ndash Step Breast Self-Exam ndash Step 22

Raise your arms and look for the Raise your arms and look for the

samesame

changeschanges

Breast Self-Exam ndash Step Breast Self-Exam ndash Step 33 Feel your breasts while lying down using Feel your breasts while lying down using

your right hand to feel your left breast and your right hand to feel your left breast and then your left hand to feel your right breast then your left hand to feel your right breast Use a firm smooth touch with the first few Use a firm smooth touch with the first few fingers of your hand keeping the fingersfingers of your hand keeping the fingers

flat and togetherflat and together

Cover the entire breast from top to Cover the entire breast from top to bottom side to sidemdashfrom your bottom side to sidemdashfrom your collarbone to the top of your abdomen collarbone to the top of your abdomen and from your armpit to your cleavageand from your armpit to your cleavage

Breast Self-Exam ndash Step Breast Self-Exam ndash Step 44

Finally feel your breasts while you are Finally feel your breasts while you are standing or sitting Many women find standing or sitting Many women find that the easiest way to feel their breasts that the easiest way to feel their breasts is when their skin is wet and slippery is when their skin is wet and slippery so they like to do this step in the so they like to do this step in the shower Cover your entire breast using shower Cover your entire breast using the same hand movements described in the same hand movements described in Step 3Step 3

InvestigationsInvestigations

Mammography (conrsquot)Mammography (conrsquot) 1048698 1048698 Standard mammography Standard mammography depends on depends on

density of the tissue and its ability to stop density of the tissue and its ability to stop xrayxray

beam from exposing film placed on the other beam from exposing film placed on the other side of the breastside of the breast

Digital mammography Digital mammography works on the same works on the same principle but there is also some ability to principle but there is also some ability to manipulate the image by computer Main manipulate the image by computer Main advantage is storage of the filmsadvantage is storage of the films

UltrasoundUltrasound

Since solid tissue andSince solid tissue and collections of fluid look thecollections of fluid look the same on mammographysame on mammography ultrasound is very useful in ultrasound is very useful in telling whether a mass istelling whether a mass is solid or fluid and if solid ifsolid or fluid and if solid if characteristics arecharacteristics are suspicioussuspicious CystCyst

MRIMRI MRI relies on completely different type of MRI relies on completely different type of

wavewave

energy a strong magnet that affects the energy a strong magnet that affects the charge incharge in

the nuclei As magnetic force is applied and the nuclei As magnetic force is applied and thenthen

released different types of tissue send back released different types of tissue send back different types of radio wavesdifferent types of radio waves

MRI can be extremely useful in very denseMRI can be extremely useful in very dense

breasts hereditary casesbreasts hereditary cases

Fine needle aspiration of a palpable mass

1048698 Fine needle aspiration takes individual cells out ofmass Can be done for palpable or non-palpablemasses Does not show architecture especially wallof duct so best used to confirm strong suspicions

Fine Needle Aspiration

C0 No epithelial cellsC1 InadequateC2 BenignC3 AtypiaC4 SuspiciousC5 Malignant

1048698 Core biopsy can also bedone on palpable and non palpableabnormalities and on microcalcifications

Core Biopsy

B1 Normal tissue unsatisfactoryB2 BenignB3 Lesion uncertain malignant potentialB4 Suspicion of malignancyB5a In situ malignancyB5b Invasive malignancy

Investigations for Investigations for metastasismetastasis

1- abdominal ultrasound1- abdominal ultrasound

2- chest x ray or CT2- chest x ray or CT

3- bone survey or bone scan3- bone survey or bone scan

Established prognostic Established prognostic factorsfactors

bull Nodal status Nodal status bull Tumor size Tumor size bull Lymph node Lymph node bull Grade Grade bull ERPR StatusERPR Statusbull Age Age bull Lymphatic invasionLymphatic invasionbull Histological tumor typeHistological tumor type bull Perinodular infiltrationPerinodular infiltration

TREATMENT OPTIONS FOR PRIMARY OPERABLE BREAST CANCER Objective Options

Local control Lumpectomy Lumpectomy with breast irradiation Mastectomy

Regional control Axillary lymph node dissection Regional irradiation

Control of occult Chemotherapymicrometastatic disease Hormone therapy

Improved function and cosmesis Breast-conserving therapy Reconstruction (immediate or delayed)

Localized breast cancer Surgery is mainstay Halsted 1882 radical mastectomy

John Hopkins

Metastatic breast cancer Systemic treatment

Radical mastectomy A Entire breast and a

chest wall muscle is removed

LNs in the level 1 (B) and level 2 (C ) and even sometimes more distant lymph node groups (D E and F) were also removed

Modified radical mastectomy (MRM)

A Entire breast is removed

Classically some lymph nodes in the level 1 (B) and level 2 (C ) were removed called an axillary lymph node dissection

MRM = simple mastectomy + ALND

Breast conserving surgery

Also called lumpectomy with safety margin with axillary clearance or sentinel lymph node biopsy

RT should be followed

Adjuvant systemic treatment

Hypothesis Eradicate micrometastasis From effective treatment for overt

(macro) metastasis

Chemotherapy Hormone therapy

Adjuvant chemotherapy

CMF first generation 1970s Cyclophosphamide Methotrexate 5-FU

Benefit in Distant recurrence Survival

Adjuvant chemotherapy

CAF or CEF 2nd generation 1980s Cyclophophamide Adramycin(or Epirubicin) 5-FU

More toxic than CMF CAF better than CMF in high-risk group

Axilla LN+ LN- but tumor large or other risk factor

Adjuvant chemotherapy

Incorporate Taxane TAC 3rd generation mid-1990s

Taxotere Adriamycin Cyclophosphamide

More toxic than CAF Better than CAF in high-risk group

Need more time to observe

Adjuvant Herceptin(HER-2 (Human Epidermal growth factor Receptor 2) also

known as proto-oncogene Neu Over expression of this gene is correlated with higher aggressiveness in breast cancer

HER2 is a cell membrane surface-bound receptor tyrosine kinase and is normally involved in the signal transduction pathways leading to cell growth and differentiation)

Effective in Her2+ pts ICH3+ FISH+

Herceptin + adjuvant chemotherapy Optimal role to be defined

Concurrent or sequential Maintenance Duration

Breast Self-Exam ndash Step Breast Self-Exam ndash Step 33 Feel your breasts while lying down using Feel your breasts while lying down using

your right hand to feel your left breast and your right hand to feel your left breast and then your left hand to feel your right breast then your left hand to feel your right breast Use a firm smooth touch with the first few Use a firm smooth touch with the first few fingers of your hand keeping the fingersfingers of your hand keeping the fingers

flat and togetherflat and together

Cover the entire breast from top to Cover the entire breast from top to bottom side to sidemdashfrom your bottom side to sidemdashfrom your collarbone to the top of your abdomen collarbone to the top of your abdomen and from your armpit to your cleavageand from your armpit to your cleavage

Breast Self-Exam ndash Step Breast Self-Exam ndash Step 44

Finally feel your breasts while you are Finally feel your breasts while you are standing or sitting Many women find standing or sitting Many women find that the easiest way to feel their breasts that the easiest way to feel their breasts is when their skin is wet and slippery is when their skin is wet and slippery so they like to do this step in the so they like to do this step in the shower Cover your entire breast using shower Cover your entire breast using the same hand movements described in the same hand movements described in Step 3Step 3

InvestigationsInvestigations

Mammography (conrsquot)Mammography (conrsquot) 1048698 1048698 Standard mammography Standard mammography depends on depends on

density of the tissue and its ability to stop density of the tissue and its ability to stop xrayxray

beam from exposing film placed on the other beam from exposing film placed on the other side of the breastside of the breast

Digital mammography Digital mammography works on the same works on the same principle but there is also some ability to principle but there is also some ability to manipulate the image by computer Main manipulate the image by computer Main advantage is storage of the filmsadvantage is storage of the films

UltrasoundUltrasound

Since solid tissue andSince solid tissue and collections of fluid look thecollections of fluid look the same on mammographysame on mammography ultrasound is very useful in ultrasound is very useful in telling whether a mass istelling whether a mass is solid or fluid and if solid ifsolid or fluid and if solid if characteristics arecharacteristics are suspicioussuspicious CystCyst

MRIMRI MRI relies on completely different type of MRI relies on completely different type of

wavewave

energy a strong magnet that affects the energy a strong magnet that affects the charge incharge in

the nuclei As magnetic force is applied and the nuclei As magnetic force is applied and thenthen

released different types of tissue send back released different types of tissue send back different types of radio wavesdifferent types of radio waves

MRI can be extremely useful in very denseMRI can be extremely useful in very dense

breasts hereditary casesbreasts hereditary cases

Fine needle aspiration of a palpable mass

1048698 Fine needle aspiration takes individual cells out ofmass Can be done for palpable or non-palpablemasses Does not show architecture especially wallof duct so best used to confirm strong suspicions

Fine Needle Aspiration

C0 No epithelial cellsC1 InadequateC2 BenignC3 AtypiaC4 SuspiciousC5 Malignant

1048698 Core biopsy can also bedone on palpable and non palpableabnormalities and on microcalcifications

Core Biopsy

B1 Normal tissue unsatisfactoryB2 BenignB3 Lesion uncertain malignant potentialB4 Suspicion of malignancyB5a In situ malignancyB5b Invasive malignancy

Investigations for Investigations for metastasismetastasis

1- abdominal ultrasound1- abdominal ultrasound

2- chest x ray or CT2- chest x ray or CT

3- bone survey or bone scan3- bone survey or bone scan

Established prognostic Established prognostic factorsfactors

bull Nodal status Nodal status bull Tumor size Tumor size bull Lymph node Lymph node bull Grade Grade bull ERPR StatusERPR Statusbull Age Age bull Lymphatic invasionLymphatic invasionbull Histological tumor typeHistological tumor type bull Perinodular infiltrationPerinodular infiltration

TREATMENT OPTIONS FOR PRIMARY OPERABLE BREAST CANCER Objective Options

Local control Lumpectomy Lumpectomy with breast irradiation Mastectomy

Regional control Axillary lymph node dissection Regional irradiation

Control of occult Chemotherapymicrometastatic disease Hormone therapy

Improved function and cosmesis Breast-conserving therapy Reconstruction (immediate or delayed)

Localized breast cancer Surgery is mainstay Halsted 1882 radical mastectomy

John Hopkins

Metastatic breast cancer Systemic treatment

Radical mastectomy A Entire breast and a

chest wall muscle is removed

LNs in the level 1 (B) and level 2 (C ) and even sometimes more distant lymph node groups (D E and F) were also removed

Modified radical mastectomy (MRM)

A Entire breast is removed

Classically some lymph nodes in the level 1 (B) and level 2 (C ) were removed called an axillary lymph node dissection

MRM = simple mastectomy + ALND

Breast conserving surgery

Also called lumpectomy with safety margin with axillary clearance or sentinel lymph node biopsy

RT should be followed

Adjuvant systemic treatment

Hypothesis Eradicate micrometastasis From effective treatment for overt

(macro) metastasis

Chemotherapy Hormone therapy

Adjuvant chemotherapy

CMF first generation 1970s Cyclophosphamide Methotrexate 5-FU

Benefit in Distant recurrence Survival

Adjuvant chemotherapy

CAF or CEF 2nd generation 1980s Cyclophophamide Adramycin(or Epirubicin) 5-FU

More toxic than CMF CAF better than CMF in high-risk group

Axilla LN+ LN- but tumor large or other risk factor

Adjuvant chemotherapy

Incorporate Taxane TAC 3rd generation mid-1990s

Taxotere Adriamycin Cyclophosphamide

More toxic than CAF Better than CAF in high-risk group

Need more time to observe

Adjuvant Herceptin(HER-2 (Human Epidermal growth factor Receptor 2) also

known as proto-oncogene Neu Over expression of this gene is correlated with higher aggressiveness in breast cancer

HER2 is a cell membrane surface-bound receptor tyrosine kinase and is normally involved in the signal transduction pathways leading to cell growth and differentiation)

Effective in Her2+ pts ICH3+ FISH+

Herceptin + adjuvant chemotherapy Optimal role to be defined

Concurrent or sequential Maintenance Duration

Breast Self-Exam ndash Step Breast Self-Exam ndash Step 44

Finally feel your breasts while you are Finally feel your breasts while you are standing or sitting Many women find standing or sitting Many women find that the easiest way to feel their breasts that the easiest way to feel their breasts is when their skin is wet and slippery is when their skin is wet and slippery so they like to do this step in the so they like to do this step in the shower Cover your entire breast using shower Cover your entire breast using the same hand movements described in the same hand movements described in Step 3Step 3

InvestigationsInvestigations

Mammography (conrsquot)Mammography (conrsquot) 1048698 1048698 Standard mammography Standard mammography depends on depends on

density of the tissue and its ability to stop density of the tissue and its ability to stop xrayxray

beam from exposing film placed on the other beam from exposing film placed on the other side of the breastside of the breast

Digital mammography Digital mammography works on the same works on the same principle but there is also some ability to principle but there is also some ability to manipulate the image by computer Main manipulate the image by computer Main advantage is storage of the filmsadvantage is storage of the films

UltrasoundUltrasound

Since solid tissue andSince solid tissue and collections of fluid look thecollections of fluid look the same on mammographysame on mammography ultrasound is very useful in ultrasound is very useful in telling whether a mass istelling whether a mass is solid or fluid and if solid ifsolid or fluid and if solid if characteristics arecharacteristics are suspicioussuspicious CystCyst

MRIMRI MRI relies on completely different type of MRI relies on completely different type of

wavewave

energy a strong magnet that affects the energy a strong magnet that affects the charge incharge in

the nuclei As magnetic force is applied and the nuclei As magnetic force is applied and thenthen

released different types of tissue send back released different types of tissue send back different types of radio wavesdifferent types of radio waves

MRI can be extremely useful in very denseMRI can be extremely useful in very dense

breasts hereditary casesbreasts hereditary cases

Fine needle aspiration of a palpable mass

1048698 Fine needle aspiration takes individual cells out ofmass Can be done for palpable or non-palpablemasses Does not show architecture especially wallof duct so best used to confirm strong suspicions

Fine Needle Aspiration

C0 No epithelial cellsC1 InadequateC2 BenignC3 AtypiaC4 SuspiciousC5 Malignant

1048698 Core biopsy can also bedone on palpable and non palpableabnormalities and on microcalcifications

Core Biopsy

B1 Normal tissue unsatisfactoryB2 BenignB3 Lesion uncertain malignant potentialB4 Suspicion of malignancyB5a In situ malignancyB5b Invasive malignancy

Investigations for Investigations for metastasismetastasis

1- abdominal ultrasound1- abdominal ultrasound

2- chest x ray or CT2- chest x ray or CT

3- bone survey or bone scan3- bone survey or bone scan

Established prognostic Established prognostic factorsfactors

bull Nodal status Nodal status bull Tumor size Tumor size bull Lymph node Lymph node bull Grade Grade bull ERPR StatusERPR Statusbull Age Age bull Lymphatic invasionLymphatic invasionbull Histological tumor typeHistological tumor type bull Perinodular infiltrationPerinodular infiltration

TREATMENT OPTIONS FOR PRIMARY OPERABLE BREAST CANCER Objective Options

Local control Lumpectomy Lumpectomy with breast irradiation Mastectomy

Regional control Axillary lymph node dissection Regional irradiation

Control of occult Chemotherapymicrometastatic disease Hormone therapy

Improved function and cosmesis Breast-conserving therapy Reconstruction (immediate or delayed)

Localized breast cancer Surgery is mainstay Halsted 1882 radical mastectomy

John Hopkins

Metastatic breast cancer Systemic treatment

Radical mastectomy A Entire breast and a

chest wall muscle is removed

LNs in the level 1 (B) and level 2 (C ) and even sometimes more distant lymph node groups (D E and F) were also removed

Modified radical mastectomy (MRM)

A Entire breast is removed

Classically some lymph nodes in the level 1 (B) and level 2 (C ) were removed called an axillary lymph node dissection

MRM = simple mastectomy + ALND

Breast conserving surgery

Also called lumpectomy with safety margin with axillary clearance or sentinel lymph node biopsy

RT should be followed

Adjuvant systemic treatment

Hypothesis Eradicate micrometastasis From effective treatment for overt

(macro) metastasis

Chemotherapy Hormone therapy

Adjuvant chemotherapy

CMF first generation 1970s Cyclophosphamide Methotrexate 5-FU

Benefit in Distant recurrence Survival

Adjuvant chemotherapy

CAF or CEF 2nd generation 1980s Cyclophophamide Adramycin(or Epirubicin) 5-FU

More toxic than CMF CAF better than CMF in high-risk group

Axilla LN+ LN- but tumor large or other risk factor

Adjuvant chemotherapy

Incorporate Taxane TAC 3rd generation mid-1990s

Taxotere Adriamycin Cyclophosphamide

More toxic than CAF Better than CAF in high-risk group

Need more time to observe

Adjuvant Herceptin(HER-2 (Human Epidermal growth factor Receptor 2) also

known as proto-oncogene Neu Over expression of this gene is correlated with higher aggressiveness in breast cancer

HER2 is a cell membrane surface-bound receptor tyrosine kinase and is normally involved in the signal transduction pathways leading to cell growth and differentiation)

Effective in Her2+ pts ICH3+ FISH+

Herceptin + adjuvant chemotherapy Optimal role to be defined

Concurrent or sequential Maintenance Duration

InvestigationsInvestigations

Mammography (conrsquot)Mammography (conrsquot) 1048698 1048698 Standard mammography Standard mammography depends on depends on

density of the tissue and its ability to stop density of the tissue and its ability to stop xrayxray

beam from exposing film placed on the other beam from exposing film placed on the other side of the breastside of the breast

Digital mammography Digital mammography works on the same works on the same principle but there is also some ability to principle but there is also some ability to manipulate the image by computer Main manipulate the image by computer Main advantage is storage of the filmsadvantage is storage of the films

UltrasoundUltrasound

Since solid tissue andSince solid tissue and collections of fluid look thecollections of fluid look the same on mammographysame on mammography ultrasound is very useful in ultrasound is very useful in telling whether a mass istelling whether a mass is solid or fluid and if solid ifsolid or fluid and if solid if characteristics arecharacteristics are suspicioussuspicious CystCyst

MRIMRI MRI relies on completely different type of MRI relies on completely different type of

wavewave

energy a strong magnet that affects the energy a strong magnet that affects the charge incharge in

the nuclei As magnetic force is applied and the nuclei As magnetic force is applied and thenthen

released different types of tissue send back released different types of tissue send back different types of radio wavesdifferent types of radio waves

MRI can be extremely useful in very denseMRI can be extremely useful in very dense

breasts hereditary casesbreasts hereditary cases

Fine needle aspiration of a palpable mass

1048698 Fine needle aspiration takes individual cells out ofmass Can be done for palpable or non-palpablemasses Does not show architecture especially wallof duct so best used to confirm strong suspicions

Fine Needle Aspiration

C0 No epithelial cellsC1 InadequateC2 BenignC3 AtypiaC4 SuspiciousC5 Malignant

1048698 Core biopsy can also bedone on palpable and non palpableabnormalities and on microcalcifications

Core Biopsy

B1 Normal tissue unsatisfactoryB2 BenignB3 Lesion uncertain malignant potentialB4 Suspicion of malignancyB5a In situ malignancyB5b Invasive malignancy

Investigations for Investigations for metastasismetastasis

1- abdominal ultrasound1- abdominal ultrasound

2- chest x ray or CT2- chest x ray or CT

3- bone survey or bone scan3- bone survey or bone scan

Established prognostic Established prognostic factorsfactors

bull Nodal status Nodal status bull Tumor size Tumor size bull Lymph node Lymph node bull Grade Grade bull ERPR StatusERPR Statusbull Age Age bull Lymphatic invasionLymphatic invasionbull Histological tumor typeHistological tumor type bull Perinodular infiltrationPerinodular infiltration

TREATMENT OPTIONS FOR PRIMARY OPERABLE BREAST CANCER Objective Options

Local control Lumpectomy Lumpectomy with breast irradiation Mastectomy

Regional control Axillary lymph node dissection Regional irradiation

Control of occult Chemotherapymicrometastatic disease Hormone therapy

Improved function and cosmesis Breast-conserving therapy Reconstruction (immediate or delayed)

Localized breast cancer Surgery is mainstay Halsted 1882 radical mastectomy

John Hopkins

Metastatic breast cancer Systemic treatment

Radical mastectomy A Entire breast and a

chest wall muscle is removed

LNs in the level 1 (B) and level 2 (C ) and even sometimes more distant lymph node groups (D E and F) were also removed

Modified radical mastectomy (MRM)

A Entire breast is removed

Classically some lymph nodes in the level 1 (B) and level 2 (C ) were removed called an axillary lymph node dissection

MRM = simple mastectomy + ALND

Breast conserving surgery

Also called lumpectomy with safety margin with axillary clearance or sentinel lymph node biopsy

RT should be followed

Adjuvant systemic treatment

Hypothesis Eradicate micrometastasis From effective treatment for overt

(macro) metastasis

Chemotherapy Hormone therapy

Adjuvant chemotherapy

CMF first generation 1970s Cyclophosphamide Methotrexate 5-FU

Benefit in Distant recurrence Survival

Adjuvant chemotherapy

CAF or CEF 2nd generation 1980s Cyclophophamide Adramycin(or Epirubicin) 5-FU

More toxic than CMF CAF better than CMF in high-risk group

Axilla LN+ LN- but tumor large or other risk factor

Adjuvant chemotherapy

Incorporate Taxane TAC 3rd generation mid-1990s

Taxotere Adriamycin Cyclophosphamide

More toxic than CAF Better than CAF in high-risk group

Need more time to observe

Adjuvant Herceptin(HER-2 (Human Epidermal growth factor Receptor 2) also

known as proto-oncogene Neu Over expression of this gene is correlated with higher aggressiveness in breast cancer

HER2 is a cell membrane surface-bound receptor tyrosine kinase and is normally involved in the signal transduction pathways leading to cell growth and differentiation)

Effective in Her2+ pts ICH3+ FISH+

Herceptin + adjuvant chemotherapy Optimal role to be defined

Concurrent or sequential Maintenance Duration

UltrasoundUltrasound

Since solid tissue andSince solid tissue and collections of fluid look thecollections of fluid look the same on mammographysame on mammography ultrasound is very useful in ultrasound is very useful in telling whether a mass istelling whether a mass is solid or fluid and if solid ifsolid or fluid and if solid if characteristics arecharacteristics are suspicioussuspicious CystCyst

MRIMRI MRI relies on completely different type of MRI relies on completely different type of

wavewave

energy a strong magnet that affects the energy a strong magnet that affects the charge incharge in

the nuclei As magnetic force is applied and the nuclei As magnetic force is applied and thenthen

released different types of tissue send back released different types of tissue send back different types of radio wavesdifferent types of radio waves

MRI can be extremely useful in very denseMRI can be extremely useful in very dense

breasts hereditary casesbreasts hereditary cases

Fine needle aspiration of a palpable mass

1048698 Fine needle aspiration takes individual cells out ofmass Can be done for palpable or non-palpablemasses Does not show architecture especially wallof duct so best used to confirm strong suspicions

Fine Needle Aspiration

C0 No epithelial cellsC1 InadequateC2 BenignC3 AtypiaC4 SuspiciousC5 Malignant

1048698 Core biopsy can also bedone on palpable and non palpableabnormalities and on microcalcifications

Core Biopsy

B1 Normal tissue unsatisfactoryB2 BenignB3 Lesion uncertain malignant potentialB4 Suspicion of malignancyB5a In situ malignancyB5b Invasive malignancy

Investigations for Investigations for metastasismetastasis

1- abdominal ultrasound1- abdominal ultrasound

2- chest x ray or CT2- chest x ray or CT

3- bone survey or bone scan3- bone survey or bone scan

Established prognostic Established prognostic factorsfactors

bull Nodal status Nodal status bull Tumor size Tumor size bull Lymph node Lymph node bull Grade Grade bull ERPR StatusERPR Statusbull Age Age bull Lymphatic invasionLymphatic invasionbull Histological tumor typeHistological tumor type bull Perinodular infiltrationPerinodular infiltration

TREATMENT OPTIONS FOR PRIMARY OPERABLE BREAST CANCER Objective Options

Local control Lumpectomy Lumpectomy with breast irradiation Mastectomy

Regional control Axillary lymph node dissection Regional irradiation

Control of occult Chemotherapymicrometastatic disease Hormone therapy

Improved function and cosmesis Breast-conserving therapy Reconstruction (immediate or delayed)

Localized breast cancer Surgery is mainstay Halsted 1882 radical mastectomy

John Hopkins

Metastatic breast cancer Systemic treatment

Radical mastectomy A Entire breast and a

chest wall muscle is removed

LNs in the level 1 (B) and level 2 (C ) and even sometimes more distant lymph node groups (D E and F) were also removed

Modified radical mastectomy (MRM)

A Entire breast is removed

Classically some lymph nodes in the level 1 (B) and level 2 (C ) were removed called an axillary lymph node dissection

MRM = simple mastectomy + ALND

Breast conserving surgery

Also called lumpectomy with safety margin with axillary clearance or sentinel lymph node biopsy

RT should be followed

Adjuvant systemic treatment

Hypothesis Eradicate micrometastasis From effective treatment for overt

(macro) metastasis

Chemotherapy Hormone therapy

Adjuvant chemotherapy

CMF first generation 1970s Cyclophosphamide Methotrexate 5-FU

Benefit in Distant recurrence Survival

Adjuvant chemotherapy

CAF or CEF 2nd generation 1980s Cyclophophamide Adramycin(or Epirubicin) 5-FU

More toxic than CMF CAF better than CMF in high-risk group

Axilla LN+ LN- but tumor large or other risk factor

Adjuvant chemotherapy

Incorporate Taxane TAC 3rd generation mid-1990s

Taxotere Adriamycin Cyclophosphamide

More toxic than CAF Better than CAF in high-risk group

Need more time to observe

Adjuvant Herceptin(HER-2 (Human Epidermal growth factor Receptor 2) also

known as proto-oncogene Neu Over expression of this gene is correlated with higher aggressiveness in breast cancer

HER2 is a cell membrane surface-bound receptor tyrosine kinase and is normally involved in the signal transduction pathways leading to cell growth and differentiation)

Effective in Her2+ pts ICH3+ FISH+

Herceptin + adjuvant chemotherapy Optimal role to be defined

Concurrent or sequential Maintenance Duration

MRIMRI MRI relies on completely different type of MRI relies on completely different type of

wavewave

energy a strong magnet that affects the energy a strong magnet that affects the charge incharge in

the nuclei As magnetic force is applied and the nuclei As magnetic force is applied and thenthen

released different types of tissue send back released different types of tissue send back different types of radio wavesdifferent types of radio waves

MRI can be extremely useful in very denseMRI can be extremely useful in very dense

breasts hereditary casesbreasts hereditary cases

Fine needle aspiration of a palpable mass

1048698 Fine needle aspiration takes individual cells out ofmass Can be done for palpable or non-palpablemasses Does not show architecture especially wallof duct so best used to confirm strong suspicions

Fine Needle Aspiration

C0 No epithelial cellsC1 InadequateC2 BenignC3 AtypiaC4 SuspiciousC5 Malignant

1048698 Core biopsy can also bedone on palpable and non palpableabnormalities and on microcalcifications

Core Biopsy

B1 Normal tissue unsatisfactoryB2 BenignB3 Lesion uncertain malignant potentialB4 Suspicion of malignancyB5a In situ malignancyB5b Invasive malignancy

Investigations for Investigations for metastasismetastasis

1- abdominal ultrasound1- abdominal ultrasound

2- chest x ray or CT2- chest x ray or CT

3- bone survey or bone scan3- bone survey or bone scan

Established prognostic Established prognostic factorsfactors

bull Nodal status Nodal status bull Tumor size Tumor size bull Lymph node Lymph node bull Grade Grade bull ERPR StatusERPR Statusbull Age Age bull Lymphatic invasionLymphatic invasionbull Histological tumor typeHistological tumor type bull Perinodular infiltrationPerinodular infiltration

TREATMENT OPTIONS FOR PRIMARY OPERABLE BREAST CANCER Objective Options

Local control Lumpectomy Lumpectomy with breast irradiation Mastectomy

Regional control Axillary lymph node dissection Regional irradiation

Control of occult Chemotherapymicrometastatic disease Hormone therapy

Improved function and cosmesis Breast-conserving therapy Reconstruction (immediate or delayed)

Localized breast cancer Surgery is mainstay Halsted 1882 radical mastectomy

John Hopkins

Metastatic breast cancer Systemic treatment

Radical mastectomy A Entire breast and a

chest wall muscle is removed

LNs in the level 1 (B) and level 2 (C ) and even sometimes more distant lymph node groups (D E and F) were also removed

Modified radical mastectomy (MRM)

A Entire breast is removed

Classically some lymph nodes in the level 1 (B) and level 2 (C ) were removed called an axillary lymph node dissection

MRM = simple mastectomy + ALND

Breast conserving surgery

Also called lumpectomy with safety margin with axillary clearance or sentinel lymph node biopsy

RT should be followed

Adjuvant systemic treatment

Hypothesis Eradicate micrometastasis From effective treatment for overt

(macro) metastasis

Chemotherapy Hormone therapy

Adjuvant chemotherapy

CMF first generation 1970s Cyclophosphamide Methotrexate 5-FU

Benefit in Distant recurrence Survival

Adjuvant chemotherapy

CAF or CEF 2nd generation 1980s Cyclophophamide Adramycin(or Epirubicin) 5-FU

More toxic than CMF CAF better than CMF in high-risk group

Axilla LN+ LN- but tumor large or other risk factor

Adjuvant chemotherapy

Incorporate Taxane TAC 3rd generation mid-1990s

Taxotere Adriamycin Cyclophosphamide

More toxic than CAF Better than CAF in high-risk group

Need more time to observe

Adjuvant Herceptin(HER-2 (Human Epidermal growth factor Receptor 2) also

known as proto-oncogene Neu Over expression of this gene is correlated with higher aggressiveness in breast cancer

HER2 is a cell membrane surface-bound receptor tyrosine kinase and is normally involved in the signal transduction pathways leading to cell growth and differentiation)

Effective in Her2+ pts ICH3+ FISH+

Herceptin + adjuvant chemotherapy Optimal role to be defined

Concurrent or sequential Maintenance Duration

Fine needle aspiration of a palpable mass

1048698 Fine needle aspiration takes individual cells out ofmass Can be done for palpable or non-palpablemasses Does not show architecture especially wallof duct so best used to confirm strong suspicions

Fine Needle Aspiration

C0 No epithelial cellsC1 InadequateC2 BenignC3 AtypiaC4 SuspiciousC5 Malignant

1048698 Core biopsy can also bedone on palpable and non palpableabnormalities and on microcalcifications

Core Biopsy

B1 Normal tissue unsatisfactoryB2 BenignB3 Lesion uncertain malignant potentialB4 Suspicion of malignancyB5a In situ malignancyB5b Invasive malignancy

Investigations for Investigations for metastasismetastasis

1- abdominal ultrasound1- abdominal ultrasound

2- chest x ray or CT2- chest x ray or CT

3- bone survey or bone scan3- bone survey or bone scan

Established prognostic Established prognostic factorsfactors

bull Nodal status Nodal status bull Tumor size Tumor size bull Lymph node Lymph node bull Grade Grade bull ERPR StatusERPR Statusbull Age Age bull Lymphatic invasionLymphatic invasionbull Histological tumor typeHistological tumor type bull Perinodular infiltrationPerinodular infiltration

TREATMENT OPTIONS FOR PRIMARY OPERABLE BREAST CANCER Objective Options

Local control Lumpectomy Lumpectomy with breast irradiation Mastectomy

Regional control Axillary lymph node dissection Regional irradiation

Control of occult Chemotherapymicrometastatic disease Hormone therapy

Improved function and cosmesis Breast-conserving therapy Reconstruction (immediate or delayed)

Localized breast cancer Surgery is mainstay Halsted 1882 radical mastectomy

John Hopkins

Metastatic breast cancer Systemic treatment

Radical mastectomy A Entire breast and a

chest wall muscle is removed

LNs in the level 1 (B) and level 2 (C ) and even sometimes more distant lymph node groups (D E and F) were also removed

Modified radical mastectomy (MRM)

A Entire breast is removed

Classically some lymph nodes in the level 1 (B) and level 2 (C ) were removed called an axillary lymph node dissection

MRM = simple mastectomy + ALND

Breast conserving surgery

Also called lumpectomy with safety margin with axillary clearance or sentinel lymph node biopsy

RT should be followed

Adjuvant systemic treatment

Hypothesis Eradicate micrometastasis From effective treatment for overt

(macro) metastasis

Chemotherapy Hormone therapy

Adjuvant chemotherapy

CMF first generation 1970s Cyclophosphamide Methotrexate 5-FU

Benefit in Distant recurrence Survival

Adjuvant chemotherapy

CAF or CEF 2nd generation 1980s Cyclophophamide Adramycin(or Epirubicin) 5-FU

More toxic than CMF CAF better than CMF in high-risk group

Axilla LN+ LN- but tumor large or other risk factor

Adjuvant chemotherapy

Incorporate Taxane TAC 3rd generation mid-1990s

Taxotere Adriamycin Cyclophosphamide

More toxic than CAF Better than CAF in high-risk group

Need more time to observe

Adjuvant Herceptin(HER-2 (Human Epidermal growth factor Receptor 2) also

known as proto-oncogene Neu Over expression of this gene is correlated with higher aggressiveness in breast cancer

HER2 is a cell membrane surface-bound receptor tyrosine kinase and is normally involved in the signal transduction pathways leading to cell growth and differentiation)

Effective in Her2+ pts ICH3+ FISH+

Herceptin + adjuvant chemotherapy Optimal role to be defined

Concurrent or sequential Maintenance Duration

1048698 Core biopsy can also bedone on palpable and non palpableabnormalities and on microcalcifications

Core Biopsy

B1 Normal tissue unsatisfactoryB2 BenignB3 Lesion uncertain malignant potentialB4 Suspicion of malignancyB5a In situ malignancyB5b Invasive malignancy

Investigations for Investigations for metastasismetastasis

1- abdominal ultrasound1- abdominal ultrasound

2- chest x ray or CT2- chest x ray or CT

3- bone survey or bone scan3- bone survey or bone scan

Established prognostic Established prognostic factorsfactors

bull Nodal status Nodal status bull Tumor size Tumor size bull Lymph node Lymph node bull Grade Grade bull ERPR StatusERPR Statusbull Age Age bull Lymphatic invasionLymphatic invasionbull Histological tumor typeHistological tumor type bull Perinodular infiltrationPerinodular infiltration

TREATMENT OPTIONS FOR PRIMARY OPERABLE BREAST CANCER Objective Options

Local control Lumpectomy Lumpectomy with breast irradiation Mastectomy

Regional control Axillary lymph node dissection Regional irradiation

Control of occult Chemotherapymicrometastatic disease Hormone therapy

Improved function and cosmesis Breast-conserving therapy Reconstruction (immediate or delayed)

Localized breast cancer Surgery is mainstay Halsted 1882 radical mastectomy

John Hopkins

Metastatic breast cancer Systemic treatment

Radical mastectomy A Entire breast and a

chest wall muscle is removed

LNs in the level 1 (B) and level 2 (C ) and even sometimes more distant lymph node groups (D E and F) were also removed

Modified radical mastectomy (MRM)

A Entire breast is removed

Classically some lymph nodes in the level 1 (B) and level 2 (C ) were removed called an axillary lymph node dissection

MRM = simple mastectomy + ALND

Breast conserving surgery

Also called lumpectomy with safety margin with axillary clearance or sentinel lymph node biopsy

RT should be followed

Adjuvant systemic treatment

Hypothesis Eradicate micrometastasis From effective treatment for overt

(macro) metastasis

Chemotherapy Hormone therapy

Adjuvant chemotherapy

CMF first generation 1970s Cyclophosphamide Methotrexate 5-FU

Benefit in Distant recurrence Survival

Adjuvant chemotherapy

CAF or CEF 2nd generation 1980s Cyclophophamide Adramycin(or Epirubicin) 5-FU

More toxic than CMF CAF better than CMF in high-risk group

Axilla LN+ LN- but tumor large or other risk factor

Adjuvant chemotherapy

Incorporate Taxane TAC 3rd generation mid-1990s

Taxotere Adriamycin Cyclophosphamide

More toxic than CAF Better than CAF in high-risk group

Need more time to observe

Adjuvant Herceptin(HER-2 (Human Epidermal growth factor Receptor 2) also

known as proto-oncogene Neu Over expression of this gene is correlated with higher aggressiveness in breast cancer

HER2 is a cell membrane surface-bound receptor tyrosine kinase and is normally involved in the signal transduction pathways leading to cell growth and differentiation)

Effective in Her2+ pts ICH3+ FISH+

Herceptin + adjuvant chemotherapy Optimal role to be defined

Concurrent or sequential Maintenance Duration

Investigations for Investigations for metastasismetastasis

1- abdominal ultrasound1- abdominal ultrasound

2- chest x ray or CT2- chest x ray or CT

3- bone survey or bone scan3- bone survey or bone scan

Established prognostic Established prognostic factorsfactors

bull Nodal status Nodal status bull Tumor size Tumor size bull Lymph node Lymph node bull Grade Grade bull ERPR StatusERPR Statusbull Age Age bull Lymphatic invasionLymphatic invasionbull Histological tumor typeHistological tumor type bull Perinodular infiltrationPerinodular infiltration

TREATMENT OPTIONS FOR PRIMARY OPERABLE BREAST CANCER Objective Options

Local control Lumpectomy Lumpectomy with breast irradiation Mastectomy

Regional control Axillary lymph node dissection Regional irradiation

Control of occult Chemotherapymicrometastatic disease Hormone therapy

Improved function and cosmesis Breast-conserving therapy Reconstruction (immediate or delayed)

Localized breast cancer Surgery is mainstay Halsted 1882 radical mastectomy

John Hopkins

Metastatic breast cancer Systemic treatment

Radical mastectomy A Entire breast and a

chest wall muscle is removed

LNs in the level 1 (B) and level 2 (C ) and even sometimes more distant lymph node groups (D E and F) were also removed

Modified radical mastectomy (MRM)

A Entire breast is removed

Classically some lymph nodes in the level 1 (B) and level 2 (C ) were removed called an axillary lymph node dissection

MRM = simple mastectomy + ALND

Breast conserving surgery

Also called lumpectomy with safety margin with axillary clearance or sentinel lymph node biopsy

RT should be followed

Adjuvant systemic treatment

Hypothesis Eradicate micrometastasis From effective treatment for overt

(macro) metastasis

Chemotherapy Hormone therapy

Adjuvant chemotherapy

CMF first generation 1970s Cyclophosphamide Methotrexate 5-FU

Benefit in Distant recurrence Survival

Adjuvant chemotherapy

CAF or CEF 2nd generation 1980s Cyclophophamide Adramycin(or Epirubicin) 5-FU

More toxic than CMF CAF better than CMF in high-risk group

Axilla LN+ LN- but tumor large or other risk factor

Adjuvant chemotherapy

Incorporate Taxane TAC 3rd generation mid-1990s

Taxotere Adriamycin Cyclophosphamide

More toxic than CAF Better than CAF in high-risk group

Need more time to observe

Adjuvant Herceptin(HER-2 (Human Epidermal growth factor Receptor 2) also

known as proto-oncogene Neu Over expression of this gene is correlated with higher aggressiveness in breast cancer

HER2 is a cell membrane surface-bound receptor tyrosine kinase and is normally involved in the signal transduction pathways leading to cell growth and differentiation)

Effective in Her2+ pts ICH3+ FISH+

Herceptin + adjuvant chemotherapy Optimal role to be defined

Concurrent or sequential Maintenance Duration

Established prognostic Established prognostic factorsfactors

bull Nodal status Nodal status bull Tumor size Tumor size bull Lymph node Lymph node bull Grade Grade bull ERPR StatusERPR Statusbull Age Age bull Lymphatic invasionLymphatic invasionbull Histological tumor typeHistological tumor type bull Perinodular infiltrationPerinodular infiltration

TREATMENT OPTIONS FOR PRIMARY OPERABLE BREAST CANCER Objective Options

Local control Lumpectomy Lumpectomy with breast irradiation Mastectomy

Regional control Axillary lymph node dissection Regional irradiation

Control of occult Chemotherapymicrometastatic disease Hormone therapy

Improved function and cosmesis Breast-conserving therapy Reconstruction (immediate or delayed)

Localized breast cancer Surgery is mainstay Halsted 1882 radical mastectomy

John Hopkins

Metastatic breast cancer Systemic treatment

Radical mastectomy A Entire breast and a

chest wall muscle is removed

LNs in the level 1 (B) and level 2 (C ) and even sometimes more distant lymph node groups (D E and F) were also removed

Modified radical mastectomy (MRM)

A Entire breast is removed

Classically some lymph nodes in the level 1 (B) and level 2 (C ) were removed called an axillary lymph node dissection

MRM = simple mastectomy + ALND

Breast conserving surgery

Also called lumpectomy with safety margin with axillary clearance or sentinel lymph node biopsy

RT should be followed

Adjuvant systemic treatment

Hypothesis Eradicate micrometastasis From effective treatment for overt

(macro) metastasis

Chemotherapy Hormone therapy

Adjuvant chemotherapy

CMF first generation 1970s Cyclophosphamide Methotrexate 5-FU

Benefit in Distant recurrence Survival

Adjuvant chemotherapy

CAF or CEF 2nd generation 1980s Cyclophophamide Adramycin(or Epirubicin) 5-FU

More toxic than CMF CAF better than CMF in high-risk group

Axilla LN+ LN- but tumor large or other risk factor

Adjuvant chemotherapy

Incorporate Taxane TAC 3rd generation mid-1990s

Taxotere Adriamycin Cyclophosphamide

More toxic than CAF Better than CAF in high-risk group

Need more time to observe

Adjuvant Herceptin(HER-2 (Human Epidermal growth factor Receptor 2) also

known as proto-oncogene Neu Over expression of this gene is correlated with higher aggressiveness in breast cancer

HER2 is a cell membrane surface-bound receptor tyrosine kinase and is normally involved in the signal transduction pathways leading to cell growth and differentiation)

Effective in Her2+ pts ICH3+ FISH+

Herceptin + adjuvant chemotherapy Optimal role to be defined

Concurrent or sequential Maintenance Duration

TREATMENT OPTIONS FOR PRIMARY OPERABLE BREAST CANCER Objective Options

Local control Lumpectomy Lumpectomy with breast irradiation Mastectomy

Regional control Axillary lymph node dissection Regional irradiation

Control of occult Chemotherapymicrometastatic disease Hormone therapy

Improved function and cosmesis Breast-conserving therapy Reconstruction (immediate or delayed)

Localized breast cancer Surgery is mainstay Halsted 1882 radical mastectomy

John Hopkins

Metastatic breast cancer Systemic treatment

Radical mastectomy A Entire breast and a

chest wall muscle is removed

LNs in the level 1 (B) and level 2 (C ) and even sometimes more distant lymph node groups (D E and F) were also removed

Modified radical mastectomy (MRM)

A Entire breast is removed

Classically some lymph nodes in the level 1 (B) and level 2 (C ) were removed called an axillary lymph node dissection

MRM = simple mastectomy + ALND

Breast conserving surgery

Also called lumpectomy with safety margin with axillary clearance or sentinel lymph node biopsy

RT should be followed

Adjuvant systemic treatment

Hypothesis Eradicate micrometastasis From effective treatment for overt

(macro) metastasis

Chemotherapy Hormone therapy

Adjuvant chemotherapy

CMF first generation 1970s Cyclophosphamide Methotrexate 5-FU

Benefit in Distant recurrence Survival

Adjuvant chemotherapy

CAF or CEF 2nd generation 1980s Cyclophophamide Adramycin(or Epirubicin) 5-FU

More toxic than CMF CAF better than CMF in high-risk group

Axilla LN+ LN- but tumor large or other risk factor

Adjuvant chemotherapy

Incorporate Taxane TAC 3rd generation mid-1990s

Taxotere Adriamycin Cyclophosphamide

More toxic than CAF Better than CAF in high-risk group

Need more time to observe

Adjuvant Herceptin(HER-2 (Human Epidermal growth factor Receptor 2) also

known as proto-oncogene Neu Over expression of this gene is correlated with higher aggressiveness in breast cancer

HER2 is a cell membrane surface-bound receptor tyrosine kinase and is normally involved in the signal transduction pathways leading to cell growth and differentiation)

Effective in Her2+ pts ICH3+ FISH+

Herceptin + adjuvant chemotherapy Optimal role to be defined

Concurrent or sequential Maintenance Duration

Localized breast cancer Surgery is mainstay Halsted 1882 radical mastectomy

John Hopkins

Metastatic breast cancer Systemic treatment

Radical mastectomy A Entire breast and a

chest wall muscle is removed

LNs in the level 1 (B) and level 2 (C ) and even sometimes more distant lymph node groups (D E and F) were also removed

Modified radical mastectomy (MRM)

A Entire breast is removed

Classically some lymph nodes in the level 1 (B) and level 2 (C ) were removed called an axillary lymph node dissection

MRM = simple mastectomy + ALND

Breast conserving surgery

Also called lumpectomy with safety margin with axillary clearance or sentinel lymph node biopsy

RT should be followed

Adjuvant systemic treatment

Hypothesis Eradicate micrometastasis From effective treatment for overt

(macro) metastasis

Chemotherapy Hormone therapy

Adjuvant chemotherapy

CMF first generation 1970s Cyclophosphamide Methotrexate 5-FU

Benefit in Distant recurrence Survival

Adjuvant chemotherapy

CAF or CEF 2nd generation 1980s Cyclophophamide Adramycin(or Epirubicin) 5-FU

More toxic than CMF CAF better than CMF in high-risk group

Axilla LN+ LN- but tumor large or other risk factor

Adjuvant chemotherapy

Incorporate Taxane TAC 3rd generation mid-1990s

Taxotere Adriamycin Cyclophosphamide

More toxic than CAF Better than CAF in high-risk group

Need more time to observe

Adjuvant Herceptin(HER-2 (Human Epidermal growth factor Receptor 2) also

known as proto-oncogene Neu Over expression of this gene is correlated with higher aggressiveness in breast cancer

HER2 is a cell membrane surface-bound receptor tyrosine kinase and is normally involved in the signal transduction pathways leading to cell growth and differentiation)

Effective in Her2+ pts ICH3+ FISH+

Herceptin + adjuvant chemotherapy Optimal role to be defined

Concurrent or sequential Maintenance Duration

Radical mastectomy A Entire breast and a

chest wall muscle is removed

LNs in the level 1 (B) and level 2 (C ) and even sometimes more distant lymph node groups (D E and F) were also removed

Modified radical mastectomy (MRM)

A Entire breast is removed

Classically some lymph nodes in the level 1 (B) and level 2 (C ) were removed called an axillary lymph node dissection

MRM = simple mastectomy + ALND

Breast conserving surgery

Also called lumpectomy with safety margin with axillary clearance or sentinel lymph node biopsy

RT should be followed

Adjuvant systemic treatment

Hypothesis Eradicate micrometastasis From effective treatment for overt

(macro) metastasis

Chemotherapy Hormone therapy

Adjuvant chemotherapy

CMF first generation 1970s Cyclophosphamide Methotrexate 5-FU

Benefit in Distant recurrence Survival

Adjuvant chemotherapy

CAF or CEF 2nd generation 1980s Cyclophophamide Adramycin(or Epirubicin) 5-FU

More toxic than CMF CAF better than CMF in high-risk group

Axilla LN+ LN- but tumor large or other risk factor

Adjuvant chemotherapy

Incorporate Taxane TAC 3rd generation mid-1990s

Taxotere Adriamycin Cyclophosphamide

More toxic than CAF Better than CAF in high-risk group

Need more time to observe

Adjuvant Herceptin(HER-2 (Human Epidermal growth factor Receptor 2) also

known as proto-oncogene Neu Over expression of this gene is correlated with higher aggressiveness in breast cancer

HER2 is a cell membrane surface-bound receptor tyrosine kinase and is normally involved in the signal transduction pathways leading to cell growth and differentiation)

Effective in Her2+ pts ICH3+ FISH+

Herceptin + adjuvant chemotherapy Optimal role to be defined

Concurrent or sequential Maintenance Duration

Modified radical mastectomy (MRM)

A Entire breast is removed

Classically some lymph nodes in the level 1 (B) and level 2 (C ) were removed called an axillary lymph node dissection

MRM = simple mastectomy + ALND

Breast conserving surgery

Also called lumpectomy with safety margin with axillary clearance or sentinel lymph node biopsy

RT should be followed

Adjuvant systemic treatment

Hypothesis Eradicate micrometastasis From effective treatment for overt

(macro) metastasis

Chemotherapy Hormone therapy

Adjuvant chemotherapy

CMF first generation 1970s Cyclophosphamide Methotrexate 5-FU

Benefit in Distant recurrence Survival

Adjuvant chemotherapy

CAF or CEF 2nd generation 1980s Cyclophophamide Adramycin(or Epirubicin) 5-FU

More toxic than CMF CAF better than CMF in high-risk group

Axilla LN+ LN- but tumor large or other risk factor

Adjuvant chemotherapy

Incorporate Taxane TAC 3rd generation mid-1990s

Taxotere Adriamycin Cyclophosphamide

More toxic than CAF Better than CAF in high-risk group

Need more time to observe

Adjuvant Herceptin(HER-2 (Human Epidermal growth factor Receptor 2) also

known as proto-oncogene Neu Over expression of this gene is correlated with higher aggressiveness in breast cancer

HER2 is a cell membrane surface-bound receptor tyrosine kinase and is normally involved in the signal transduction pathways leading to cell growth and differentiation)

Effective in Her2+ pts ICH3+ FISH+

Herceptin + adjuvant chemotherapy Optimal role to be defined

Concurrent or sequential Maintenance Duration

Breast conserving surgery

Also called lumpectomy with safety margin with axillary clearance or sentinel lymph node biopsy

RT should be followed

Adjuvant systemic treatment

Hypothesis Eradicate micrometastasis From effective treatment for overt

(macro) metastasis

Chemotherapy Hormone therapy

Adjuvant chemotherapy

CMF first generation 1970s Cyclophosphamide Methotrexate 5-FU

Benefit in Distant recurrence Survival

Adjuvant chemotherapy

CAF or CEF 2nd generation 1980s Cyclophophamide Adramycin(or Epirubicin) 5-FU

More toxic than CMF CAF better than CMF in high-risk group

Axilla LN+ LN- but tumor large or other risk factor

Adjuvant chemotherapy

Incorporate Taxane TAC 3rd generation mid-1990s

Taxotere Adriamycin Cyclophosphamide

More toxic than CAF Better than CAF in high-risk group

Need more time to observe

Adjuvant Herceptin(HER-2 (Human Epidermal growth factor Receptor 2) also

known as proto-oncogene Neu Over expression of this gene is correlated with higher aggressiveness in breast cancer

HER2 is a cell membrane surface-bound receptor tyrosine kinase and is normally involved in the signal transduction pathways leading to cell growth and differentiation)

Effective in Her2+ pts ICH3+ FISH+

Herceptin + adjuvant chemotherapy Optimal role to be defined

Concurrent or sequential Maintenance Duration

Adjuvant systemic treatment

Hypothesis Eradicate micrometastasis From effective treatment for overt

(macro) metastasis

Chemotherapy Hormone therapy

Adjuvant chemotherapy

CMF first generation 1970s Cyclophosphamide Methotrexate 5-FU

Benefit in Distant recurrence Survival

Adjuvant chemotherapy

CAF or CEF 2nd generation 1980s Cyclophophamide Adramycin(or Epirubicin) 5-FU

More toxic than CMF CAF better than CMF in high-risk group

Axilla LN+ LN- but tumor large or other risk factor

Adjuvant chemotherapy

Incorporate Taxane TAC 3rd generation mid-1990s

Taxotere Adriamycin Cyclophosphamide

More toxic than CAF Better than CAF in high-risk group

Need more time to observe

Adjuvant Herceptin(HER-2 (Human Epidermal growth factor Receptor 2) also

known as proto-oncogene Neu Over expression of this gene is correlated with higher aggressiveness in breast cancer

HER2 is a cell membrane surface-bound receptor tyrosine kinase and is normally involved in the signal transduction pathways leading to cell growth and differentiation)

Effective in Her2+ pts ICH3+ FISH+

Herceptin + adjuvant chemotherapy Optimal role to be defined

Concurrent or sequential Maintenance Duration

Adjuvant chemotherapy

CMF first generation 1970s Cyclophosphamide Methotrexate 5-FU

Benefit in Distant recurrence Survival

Adjuvant chemotherapy

CAF or CEF 2nd generation 1980s Cyclophophamide Adramycin(or Epirubicin) 5-FU

More toxic than CMF CAF better than CMF in high-risk group

Axilla LN+ LN- but tumor large or other risk factor

Adjuvant chemotherapy

Incorporate Taxane TAC 3rd generation mid-1990s

Taxotere Adriamycin Cyclophosphamide

More toxic than CAF Better than CAF in high-risk group

Need more time to observe

Adjuvant Herceptin(HER-2 (Human Epidermal growth factor Receptor 2) also

known as proto-oncogene Neu Over expression of this gene is correlated with higher aggressiveness in breast cancer

HER2 is a cell membrane surface-bound receptor tyrosine kinase and is normally involved in the signal transduction pathways leading to cell growth and differentiation)

Effective in Her2+ pts ICH3+ FISH+

Herceptin + adjuvant chemotherapy Optimal role to be defined

Concurrent or sequential Maintenance Duration

Adjuvant chemotherapy

CAF or CEF 2nd generation 1980s Cyclophophamide Adramycin(or Epirubicin) 5-FU

More toxic than CMF CAF better than CMF in high-risk group

Axilla LN+ LN- but tumor large or other risk factor

Adjuvant chemotherapy

Incorporate Taxane TAC 3rd generation mid-1990s

Taxotere Adriamycin Cyclophosphamide

More toxic than CAF Better than CAF in high-risk group

Need more time to observe

Adjuvant Herceptin(HER-2 (Human Epidermal growth factor Receptor 2) also

known as proto-oncogene Neu Over expression of this gene is correlated with higher aggressiveness in breast cancer

HER2 is a cell membrane surface-bound receptor tyrosine kinase and is normally involved in the signal transduction pathways leading to cell growth and differentiation)

Effective in Her2+ pts ICH3+ FISH+

Herceptin + adjuvant chemotherapy Optimal role to be defined

Concurrent or sequential Maintenance Duration

Adjuvant chemotherapy

Incorporate Taxane TAC 3rd generation mid-1990s

Taxotere Adriamycin Cyclophosphamide

More toxic than CAF Better than CAF in high-risk group

Need more time to observe

Adjuvant Herceptin(HER-2 (Human Epidermal growth factor Receptor 2) also

known as proto-oncogene Neu Over expression of this gene is correlated with higher aggressiveness in breast cancer

HER2 is a cell membrane surface-bound receptor tyrosine kinase and is normally involved in the signal transduction pathways leading to cell growth and differentiation)

Effective in Her2+ pts ICH3+ FISH+

Herceptin + adjuvant chemotherapy Optimal role to be defined

Concurrent or sequential Maintenance Duration

Adjuvant Herceptin(HER-2 (Human Epidermal growth factor Receptor 2) also

known as proto-oncogene Neu Over expression of this gene is correlated with higher aggressiveness in breast cancer

HER2 is a cell membrane surface-bound receptor tyrosine kinase and is normally involved in the signal transduction pathways leading to cell growth and differentiation)

Effective in Her2+ pts ICH3+ FISH+

Herceptin + adjuvant chemotherapy Optimal role to be defined

Concurrent or sequential Maintenance Duration

Adjuvant hormone therapy

In premenopausal woman Oophorectomy could control metastatic

disease

Tamoxifen Selective estrogen receptor antagonist Effective in pre- and post-menopausal Effective in adjuvant setting

Adjuvant hormone therapy

Aromatase inhibitor Effective in post-menopausal state Aromatase in fat tissue

Convert androgen to estrogen Main estrogen source in post-menopausal

Exemestane Aromasin Letrozole Femara Anastrozole Arimidex

More effective than Tamoxifen

Adjuvant ovarian suppression

Effective in pre-menopausal state Type

Surgical ablation RT ablation GnRH analogue Goserelin Leupride

Exact role to be defined Combination with chemotherapy Combination with AI or TAM

Radiation therapy Radiation kills the cancer cells left after surgery Radiation therapy doesnt make you radio active Radiation is painless when itrsquos delivered but it will

become more painful over time Treatments will be given up to 5-7 weeks 5 days a week Treatments only take frac12 hour so you can keep your

routine Your hair wonrsquot fall out unless you are also taking

chemotherapy Your skin in the area may become red and easily irritated You may feel tired even after its over Radiation after surgery reduces the chances of the cancer

reoccurring

Treatment of metastatic dz

Usual sites bone lung liver brain Incurable

Goal live with dz for longest time

Systemic treatment is mainstay Chemotherapy Hormone therapy

Palliative local therapy Radiotherapy Palliative surgery

Adjuvant hormone therapy

Aromatase inhibitor Effective in post-menopausal state Aromatase in fat tissue

Convert androgen to estrogen Main estrogen source in post-menopausal

Exemestane Aromasin Letrozole Femara Anastrozole Arimidex

More effective than Tamoxifen

Adjuvant ovarian suppression

Effective in pre-menopausal state Type

Surgical ablation RT ablation GnRH analogue Goserelin Leupride

Exact role to be defined Combination with chemotherapy Combination with AI or TAM

Radiation therapy Radiation kills the cancer cells left after surgery Radiation therapy doesnt make you radio active Radiation is painless when itrsquos delivered but it will

become more painful over time Treatments will be given up to 5-7 weeks 5 days a week Treatments only take frac12 hour so you can keep your

routine Your hair wonrsquot fall out unless you are also taking

chemotherapy Your skin in the area may become red and easily irritated You may feel tired even after its over Radiation after surgery reduces the chances of the cancer

reoccurring

Treatment of metastatic dz

Usual sites bone lung liver brain Incurable

Goal live with dz for longest time

Systemic treatment is mainstay Chemotherapy Hormone therapy

Palliative local therapy Radiotherapy Palliative surgery

Adjuvant ovarian suppression

Effective in pre-menopausal state Type

Surgical ablation RT ablation GnRH analogue Goserelin Leupride

Exact role to be defined Combination with chemotherapy Combination with AI or TAM

Radiation therapy Radiation kills the cancer cells left after surgery Radiation therapy doesnt make you radio active Radiation is painless when itrsquos delivered but it will

become more painful over time Treatments will be given up to 5-7 weeks 5 days a week Treatments only take frac12 hour so you can keep your

routine Your hair wonrsquot fall out unless you are also taking

chemotherapy Your skin in the area may become red and easily irritated You may feel tired even after its over Radiation after surgery reduces the chances of the cancer

reoccurring

Treatment of metastatic dz

Usual sites bone lung liver brain Incurable

Goal live with dz for longest time

Systemic treatment is mainstay Chemotherapy Hormone therapy

Palliative local therapy Radiotherapy Palliative surgery

Radiation therapy Radiation kills the cancer cells left after surgery Radiation therapy doesnt make you radio active Radiation is painless when itrsquos delivered but it will

become more painful over time Treatments will be given up to 5-7 weeks 5 days a week Treatments only take frac12 hour so you can keep your

routine Your hair wonrsquot fall out unless you are also taking

chemotherapy Your skin in the area may become red and easily irritated You may feel tired even after its over Radiation after surgery reduces the chances of the cancer

reoccurring

Treatment of metastatic dz

Usual sites bone lung liver brain Incurable

Goal live with dz for longest time

Systemic treatment is mainstay Chemotherapy Hormone therapy

Palliative local therapy Radiotherapy Palliative surgery

Treatment of metastatic dz

Usual sites bone lung liver brain Incurable

Goal live with dz for longest time

Systemic treatment is mainstay Chemotherapy Hormone therapy

Palliative local therapy Radiotherapy Palliative surgery