Breast cancer

Reham abdulmonem, MD

EpidemiologyEpidemiology

Breast cancer is the most frequently diagnosed cancer in women in United States excluding the skin.

A total of 211,300 cases and 39,800 deaths per year.

Second leading cause of deaths in women.

Worlwide 1 million cases are seen annually.

Primarily due to increased utilization of screening mammography, breast cancer incidence rates increased rapidly in the 1980s.

Table 1 Ten Most Common Cancers among Saudis, 2004 (All Ages

Anatomy of breast

•It extends from 2nd to 6th rib

•Covered by pectoralis muscle that is inserted in the acromian process of the scapula

AnatomyAnatomy

• Medial and Lateral Borders of breast tissue typically the sternum & mid axillary line.

• Cranial and Caudal borders typically the 2nd anterior rib & 6th anterior rib.

• Primary lymphatic drainage is to axillary, internal mammary and SCV nodes.

Anatomy of the Breast

Regional Lymph Nodes:Regional Lymph Nodes:

1.1. AxillaryAxillary

2.2. SupraclavicularSupraclavicular

3.3. Internal mammaryInternal mammary

Anatomy LN drainage

•1 .Axillary (ipsilateral) :•a. Level I (low axilla): lymph nodes lateral to

the lateral border of pec minor.•b. Level II (midaxilla): lymph nodes between

the medial & lateral borders of pec minor •c. Level III (apical axilla): lymph nodes medial

to the medial margin of the pec minor muscle•2 .Internal mammary (ipsilateral): along the

edge of the sternum in the endothoracic fascia

Axillary Lymph nodes

Breast cancer

►►Incidence:Incidence: • The most common cancer among womenThe most common cancer among women• Accounts for 30% of all female cancersAccounts for 30% of all female cancers• Increases with age Increases with age (> 50 years, 75% in postmenopausal)(> 50 years, 75% in postmenopausal)

►► Risk Factors:Risk Factors: • Hereditary:Hereditary: +ve family history in 15% +ve family history in 15%

• Tumor suppressor genesTumor suppressor genes (e.g. (e.g. BRACA-1, BRACA-2BRACA-1, BRACA-2))

• Hormones:Hormones: endogenous exposure to estrogen and progesteroneendogenous exposure to estrogen and progesterone• Early menarche, Early menarche, • Late menopause, Late menopause, • Delayed childbirth, and Delayed childbirth, and • Postmenopausal obesityPostmenopausal obesity

Risk Factors-Age

•Age plays a major role in breast cancer risk.In women under 30, breast cancer is extremely

uncommon .•The incidence of breast cancer in women aged 35

to 39 was 59 per 100,000; however, in women 55 to 59, the incidence was 296 per 100,000 .

•Breast cancer increases steeply with age until menopause. After menopause, although the incidence continues to increase, the rate of increase decreases to approximately one-sixth of that seen in

the premenopausal period.

Risk Factors-Familial

•The majority of women diagnosed with breast cancer do not have a family member with the disease.

•Only 5% to 10% have a true hereditary predisposition to breast cancer .

•Overall, the risk of developing breast cancer is increased 1.5- to 3.0-fold if a woman has a mother or sister with breast cancer.

Risk Factors-hereditary•The possibility of a mutation in either

BRCA1 or BRCA2 should be considered when breast cancer is diagnosed at a young age (i.e., less than 45 to 55), when multiple relatives are affected, when there is a history of other cancers in the family (particularly ovarian cancer), or any combination of these factors.

• THESE ARE GENETIC FACTORS

Pathology

►► Adenocarcinoma: 90%Adenocarcinoma: 90%• Ductal: 80%Ductal: 80%• Lobular: 10%Lobular: 10%

Breast CancerBreast Cancer

►► Special types: <10%Special types: <10% • Papillary carcinoma• Mucinous carcinoma• Medullary carcinoma

►► Inflammatory carcinoma: 1%Inflammatory carcinoma: 1%• Poorest prognosis

Pathology

•OTHERS

•DCIS ------in ducts

•LCIS--------in lobules

DCIS-clinical presentation

• An abnormal mammographic report of clustered microcalcifications is currently

the most common presentation of DCIS .

•DCIS can also present as a mass or pathologic nipple discharge, or can be identified as an incidental finding in a

breast biopsy .

DCIS

•Mastectomy is a curative treatment for 98% to 99%.

DCIS-conservative ttt B17

•818 women were randomized to excision alone or excision plus 5000 cGy of irradiation to the

breast .•At 90 months of follow-up,The 8-year incidence

of invasive recurrence was significantly reduced from 13.4% to 3.9% by irradiation, and the incidence of recurrent DCIS was also

significantly reduced from 13.4% to 8.2% .

DCIS Tamoxifen NSABP-24

•1804 patients with DCIS treated by lumpectomy and RT were randomized to tamoxifen (20 mg daily) or placebo for 5 years.

•Follow-up of 62 months,the risk of ipsilateral recurrence of any type (invasive or noninvasive) or of new contralateral breast cancers was

reduced from 13.0% to 8.8% at 5 years ,

LCIS

•LCIS is not detectable on macroscopic examination and is always an incidental microscopic finding in breast tissue removed for another reason

•80% to 90% of cases of LCIS occurring in premenopausal women

•LCIS is frequently noted to be bilateral ,.•LCIS is associated with an increased risk

for the development of breast carcinoma that is approximately seven to ten times equal in

both breasts.

LCIS ttt

•management option for the woman with LCIS is careful observation ,

•The use of tamoxifen in women electing observation only.

•Wide surgical excision and histologically negative margins are not needed when careful follow-up is chosen given that LCIS is known to be a multifocal lesion. Similarly, RT has no role

in the management of LCIS. assumes.

T classification

•The pathologic tumor size for classification (T) is a measurement of only the invasive

component .•Microinvasion is the extension of cancer cells

beyond the basement membrane into the adjacent tissues with no focus more than 0.1 cm

in greatest dimension .•Multiple Simultaneous Ipsilateral Primary

Carcinomas,the largest primary carcinoma to classify T .

T staging

•T1-------TUMOUR LESS THAN 2CM

•T2-------TUMOUR FROM 2-5CM

•T3--------TUMOUR MORE THAN 5CM

•T4--------TUMOUR INVADES ADJACENT STRUCTURES AS SKIN ,CHEST WALL

Staging I & II

III A , B

III C , IV

N1

•pN1a micro•> 0.2 cm

•pN1b macro>0.2 cm–pN1bi 1-3 LN

any>0.2cm,all<2.0cm–pN1bii>4LN

–pN1biii ECE <2 cm–pN1biv >2cm

•pN1mi <0.2cm>0.2mm

•pN1:1-3 and /or IM ( mic) detected by lymphscintigraphy

–pN1a 1-3 LN–pN1bIM (mic)–pN1c both a+b

N2

–pN2 ipsilateral axillary fixed to one another

•pN2:4-9 axillary nodes or clinically apparent IM in absence of axillary nodes

–pN2a 4-9 axillary nodes

–pN2bclinically apparent IM

N3

•pN3 ipsilateral internal mammary

•pN3a:>10 axillary LN or infraclav

•pN3b Or Clinically apparent IM in the presence of positive axillary nodes

•pN3b Or >3 axillary LN in the presence of microscopic diseasein IM

•pN3c Or Ipsilateral Supraclav

M---METASTASIS

•MO----NO METS

•M1-----METS POSITIVE

PrognosisPrognosis

Diagnosis

►► Symptoms & SignsSymptoms & Signs::• Breast lump:Breast lump: solitary, unilateral, hard, irregular, nontendersolitary, unilateral, hard, irregular, nontender

• Nipple discharge:Nipple discharge: bloody and unilateral ( >50 years)bloody and unilateral ( >50 years)

• Others: Others: •Local: Local: skin changesskin changes•Regional: Regional: axillary lymphadenopathyaxillary lymphadenopathy•Distant: Distant: metastases metastases

Breast CancerBreast Cancer

►► Breast Imaging:Breast Imaging: • Mammography: Mammography: detects 85% detects 85% • Ultrasonography: Ultrasonography: women under 30 yearwomen under 30 year• MRI: MRI: if mammography and ultrasound are normalif mammography and ultrasound are normal

►► Breast Biopsy: Breast Biopsy: FNA cytology or excisionalFNA cytology or excisional

►► Staging Procedures: Staging Procedures: for invasive breast cancerfor invasive breast cancer

Mammography

Signs of malignancy:

• Clustered microcalcification

• Irregular or speculated mass

• solid mass with ill-defined borders

• enlarging solid mass

• development of density when compared with a previous mammogram

A BIOPSY IS MANDATORY FROM A DISCRETE MASS EVEN IF MAMMOGRAPHY

IS FREE OR LACK OF GROWTH OVER TIME

HOW

DIAGNOSTIC PROCEDURES (A)

FNAC: SHOULD BE DONE BEFORE SURGERY SO AS TO HELP THE SURGEON DEFINE THE SURGICAL PROCEDURE. BUT STILL IF NEGATIVE , EXCISION BIOPSY IS MANDATORY

(B)Open biopsy

• UNLESS THE LESION IS BIG, EXCISION OF THE WHOLE MASS WITH SAFTEY MARGINS SHOULD BE DONE

(C)

IF NO MASSES ARE FELT • A SMALL MASS IS ONLY DETECTED BY

MAMMOGRAPHY, THEN WIRE LOCALISATION IS DONE BY RADIOLOGIST AND SOMETIMES INJECTION OF METHYLENE BLUE .

• In all cases a follow up mammography should be done after 2 months to be sure that the mass was excised

On the pathological specimen

ER&PR

Ploidy

Huer2/ne

Cathepsin D

Metastatic work-upMetastatic work-up• chest x-ray• Abd. And pelvic ultrasound • bone scan if lymph nodes are detected, T3 or

sites of severe bone tenderness

ManagementManagement

SURGERY

•Types:•Conservative lumpectomy

• quadrantectomy• wide local excision

•Modified radical mastectomy•Palliative mastectomy eg.simple

mastectomy

SURGICAL TREATMENT Conservative surgery

Axillary dissection + P/O radiation is a must

Clinical indications

• mass less than 4 cm

• age above 35 yrs

Absolute contra-indications:• multicenteric tumors• inadequate safety margins• Diffuse micro – calcifications• Pregnancy 1st, 2nd trimenster• Previous radiotherapy• Active SLE,Scleroderma

Breast-reconstructive TechniqueBreast-reconstructive Technique • Saline

implant

• Myocutanous flap ( TRAM ) flap or a latissimus dorsi flap.

Surgery-MRM

•Involve complete removal of the breast, the underlying pectoral fascia, and some of the axillary nodes.sparing the muscles

•The switch to modified radical mastectomy occurred when it became recognized that treatment failure after breast cancer surgery usually is caused by the systemic dissemination of cancer cells before surgery, rather than an

inadequate operative procedure .

Axillary dissection Sentinel LN

Definition The first node in the

lymphatic basin that recieves primary lymphatic flow.

Indications• T1-T2• LN –VE• No multifocality• No prior neoadjuvant cth

Tech

Tc99. Sulfur colloid, methylene blue ,or both. peritumoral,

IMH, PCR

St gallen…

-ve axillary SNB is now accepted as allowing avoidance of axillary dissection

Reconstruction

•The incidence of local failure in patients undergoing breast reconstruction appears to be comparable with patients treated

by mastectomy alone .

•Detection of local recurrence is not altered by immediate reconstruction.

Indications for PORT

•Postoperative RT may be given to improve local control or to improve survival. Patients with four or more positive lymph nodes should receive postoperative RT

•Primary tumor >4 cm

RadiotherapyRadiotherapyPost BCT• In >4 positive axillary LN , RT is given

to breast + SCV

( NCCN category 1 ).

• In 1-3 positive axillary LN, RT is given to breast, SCV radiation is controversial

( NCCN category 2B ).

• If negative LN, RT is given to the

breast.

MANAGEMENT OF EARLY BREAST CANCER

BCT vs Mastectomy • NSABP BO6 ; randomised 1406 pts between mastectomy

and BCT. 12y OAS=62% in both arms ,distant mets 49% vs 50% .other trials give same results. 25ys update concluded that 2nd malignancy was 2% vs 3% respectively.

• NSABP BO6 randomised 1137 pts (maximum tumor size 4cm ,l.n +ve in 37% of pts) between BCT with and without RT ; local failure was 11% vs 37%, DM was 40% vs 44%. 25 years update local rec was 14% vs 39% with significant increase in OAS.

• Conclusion:if T1-2 N0-1 CONSEVATIVE SURGERY +XRT =MRM+XRT

Mastectomy + RT in T1, T2 N0

NO however• Retrospective analysis of 1790 patients (T1, T2 N0)

performed mastectomy with PORT compared to patients performed mastectomy alone

• Proved absolute improvement of OS by 2.5 : 6.9% in patients received RT

• Prospective trials are needed to prove this hypothesis and to estimate the benefit.

CHEMOTHERAPY

•GIVEN IN ALL CASES IF THE TUMOUR IS MORE THAN 1CM

•Types:

•Taxane based

•Anthracycline based

Type of chemotherapy

• FAC/FEC

• AC

• CMF (not in Her2/neu +)

• TAXAINES ( SINGLE AGENT OR TAC) more important 4-9 LN +

Treatment policy

LN- LN+

Minimal risk Average risk

ER+ER-

ER+ ER-

TAMNONE

CTH

CTH+TAMTAM

TAM+goserlin

Chemotherapy effect EBCTCG metaanalysis ON 50000 PATIENTS SHOWED IMPROVEMENT OF OAS

AGELN -veLN +ve

50Y7%11%

50-70Y2%3%

Hormonal treatment

Mode of action

Decrease tumour growth by

• decreasing E

• Blocking the receptors

Modulate TGFα, and β or IGF1

Modulation of signaling protein (protein kinase c ‘’PKC’’)and other cell components involved in apoptosis.

estrogen

hypothalamus

Pitutary gland

Adrenal gland

ovary

GnRH

androstendione

estradiol

AromataseFSH, LH

Tumour cell

E receptor

nucleus

Tumour proliferation

and growth

ACTH

Commonly used• Oopherectomy in premenopausal by (surgical

ovariectomy, medical by Gn RH analogue and RT) so decreasing estrogen

• Selective ER modulator SERMs anti estrogens (Tamoxifene, tormefene, raloxifene, idoxifene, and arzoxifene) by occupying estrogen receptor

BREAST CANCER

PATIENTS

30% ONLYRESPOND

TOHORMONAL

TTT

WHY

Parameters reflecting hormone sensitivity:

HR+ve, G., site of mets.,HER2 concentration

BREAST CANCER

PATIENTSER+

50 : 60% ONLY

RESPONDTO HORMONAL

TTT

.

Hormonal ttt lines

2 nd line1 st line

postmenopausalpremenopausal

Gn RH analogue

RT oophrectomy

surg. ovarectomy

tam

combinations

Tam

now

aromatase inhibitor

aromatase inhibitor

Duration of hormonal ttt

EBCTCG metanalysis

of randomised trials

5y >2y >1y

NSABP B14 2001

no benefit from duration

to 10 y

CombinationsHORMONAL + RADIOTHERAPY Sequential not concurrent due to pulmonary fibrosis (old theory)

HORMONAL + CHEMOTHERAPY now concurrent…….as hormonal ttt• interfere with lipid memberane so diffusion of CT• alter Ca++ channels so diffusion of CT• high incidence of thromboembolic diseases

Management of advanced breast cancer

•T3-4N+VE OR –VE

COMBINATION OF TRAETMENTNeoadjuvant chemotherapy todown stage the tumour for possibility of conservative surgery followed by xrt+/-hormonal

Surgery followed by post operative chemo and xrt

Role of Radiotherapy

►► Conservative therapy: Conservative therapy: • In selected casesIn selected cases• Tumor excision + axillary dissection (or sentinel node)Tumor excision + axillary dissection (or sentinel node)• Radiotherapy is mandatory Radiotherapy is mandatory • Results:Results:

• Cosmetic : good to excellentCosmetic : good to excellent• Survival rates: equal to those obtained with mastectomySurvival rates: equal to those obtained with mastectomy

Breast CancerBreast Cancer

►► Postmastectomy (adjuvant):Postmastectomy (adjuvant):• To decrease risk of loco-regional recurrence rates ??To decrease risk of loco-regional recurrence rates ??

►► Preoperative (neoadjuvant): Preoperative (neoadjuvant): • To shrink the tumor in locally advanced diseaseTo shrink the tumor in locally advanced disease

►► Metastatic disease: Metastatic disease: Palliative (bone, brain metastases) Palliative (bone, brain metastases)

Radiotherapy Techniques-1►► Target Volumes: Target Volumes: • Intact breast and/or chest wallIntact breast and/or chest wall• ± Regional LN(s): axilla, supraclavicular and internal ± Regional LN(s): axilla, supraclavicular and internal mammary mammary

Breast CancerBreast Cancer

►► Patient positioning & immobilization:Patient positioning & immobilization:• The arm of involved side: elevated above the headThe arm of involved side: elevated above the head• The face turned away from the involved sideThe face turned away from the involved side

►► Methods: Methods: • External Beam:External Beam:

• Photons: megavoltage, 6 MVPhotons: megavoltage, 6 MV• Electron: boost in conservative therapy, or chest wallElectron: boost in conservative therapy, or chest wall

• Brachytherapy: interstitial (boost in conservative therapy)Brachytherapy: interstitial (boost in conservative therapy)

Simulation & Field DesignSimulation & Field Design• Supine, ipsilateral arm abducted and externally rotated and head

turned to contralateral side.

• Medial border at mid-sternum, lateral border placed 2 cm beyond all palpable breast tissue, inferior border is 2 cm from inframammary fold and superior border is at head of clavicle or 2nd intercostal space.

Radiotherapy Techniques-2Breast CancerBreast Cancer

►► Fields arrangement: Fields arrangement: • The breast and chest wall: two opposed tangential fieldsThe breast and chest wall: two opposed tangential fields• The supraclavicular and axillary nodes: anterior fieldThe supraclavicular and axillary nodes: anterior field• The internal mammary nodes: either included within The internal mammary nodes: either included within medial tangential field or in an anterior fieldmedial tangential field or in an anterior field

►► Dose /Time / Fractionation:Dose /Time / Fractionation:• 50 Gy in 25 fractions over 5 weeks: for microscopic 50 Gy in 25 fractions over 5 weeks: for microscopic subclinical diseasesubclinical disease• + 15 -20 Gy (boost) : tumor bed (conservative therapy)+ 15 -20 Gy (boost) : tumor bed (conservative therapy)

►► Beam Modifications:Beam Modifications:• Wedges within the tangential fieldsWedges within the tangential fields• Angulations of anterior supraclavicular field 15Angulations of anterior supraclavicular field 15oo ? ?• Problem of Matching Fields ?Problem of Matching Fields ?

Tangential fieldsTangential fields

Anterior FieldAnterior Field

))supraclavicular & axillary nodessupraclavicular & axillary nodes((

Simulation of tangential fieldsSimulation of tangential fields

Medial tangential field & skin reactionMedial tangential field & skin reaction

Chest wall treated with anterior electron beamChest wall treated with anterior electron beam

Radiotherapy techniques

Tangential fieldsTangential fields

Breast irradiation two tangential oppose fieldsBreast irradiation two tangential oppose fields

Skin marks of the treatment fields, left breastSkin marks of the treatment fields, left breast

Different Radiotherapy TechniquesDifferent Radiotherapy Techniques

• 3 D Conformal radiotherapy

• IMRT

• Multicatheter Interstitial implant technique

Cont. Different Radiotherapy TechniquesCont. Different Radiotherapy Techniques

• Mammosite

• Intraoperative Accelerated Partial Breast Irradiation

Radiation TechniquesRadiation Techniques• Dose prescription

• Dose prescribed 45-50 Gy at 1.8-2 Gy/fr to whole breast with tangential fields and to supraclavicular fossa ( when included ).

• Boost irradiation with electrons to bring total tumor bed dose to 60-66 Gy in all pts underwent BCT and in post mastectomy pts with positive or closed margin.

Radiation TechniquesRadiation Techniques• Dose prescription

• Each field should be treated on a daily basis over the week day.

• Bolus is used in locally advanced breast cancer

• RT can usually begin within 2-4 weeks of surgery and 3-4 weeks after last cycle of chemotherapy.

ComplicationComplication

• Cosmetic

• Arm Edema

• Pneumonitis

• Brachial Plexus Damage

• 2nd Malignancy

ComplicationComplication

•Skin reactions: 4 grades

•Erythema

•Darkdiscolouration

•Dry desquamation

•Wet desquamation

Follow up• Every 3 to 6 months for 3 years, then every

6 to 12 months for 3 years then every year• Good history taking with physical

examination , with mammography every year

• Not routinely recommended for asymptomatic patients: CXR, Abd . ultra, bone scan & tumor markers