Malignant diseases of the breast

Michael G. HalaskaDept. of Obstetrics and Gynecology

2nd Medical Faculty, Charles University

 

I. The breast

reproducion - nutrition

secondary sexual sign - maturition of the women, important role in sexual life

S. Freud – the role of the breast in the satisfaction of oral libido

II. The structure of the gland

15-20 lobus, which is divided into 20-40 lobulus basic structure of the gland: terminal

ductolobular unit (TDLU)          - consists of acini and terminal

intralobular duct         - hormonally sensitive, estrogens - ductus,

progesteron, prolaktin - lobus         - size 0,3-0,6 mm (10-100/lobulus)        

II. Structure - TDLU

II. Structure - arterial supply

rr. perforantes from a. mammaria interna

(a. thoracica interna) a. mammaria externa

(a. thoracica lateralis) a. thoracoacromialis a. thoracica suprema

(a. axillaris)

II. Structure - venous supply

circulus Luschke circulus Halleri

(under the areola)

II. Structure- lympahytic supply

lateral parts along a. thoracica lateralis into the axilla

upper parts to the apical axilla and subclavicular lymph n.

internal parts -

a. thoracica interna -

mediastinal lymph n.

III. Examination methods

self-examination (2-3 cm) physical exam – aspection, palpation (1-2cm) US - excellent differenciation between

solid and cystic structure- complementory to MG,young

women with higher density of the gland

- pregnant women MRI, CT, SPECT, PET ductography

III. Examination methods

cytology

a) secretory: from the nipple

b) punction (FNA)

- not by an suspition of malignity

- 15-20% false negativebenign malign

III. Examination methods

punctional biopsy – core-cut biopsy open biopsy

III. Examination methods

c) Mammotome- vacuum assisted- not possible to evaluate

the bordersd) ABBI - 3D localisation- 20 mm diameter- possible to evaluate the borders

III. Exam. m.- mammography

over 35 y. detection ability: from 1-3 mm dose 0,1-0,2 rad

a) screening: 1. entry 35-40 y, 2. 40-50 y every 2 y.,3. over 50 y every 1 y (- 75 y.)

- mortality reduction 20-45%b) diagnostic

III. Exam. m.- mammography

III. Exam. m.- mammography

1a. Fibroadenoma

round, well circumscribed from lobulus proliferation of epithelial and stromal

components hormonally dependent a) pericanalicular b) intracanalicular

1b. Fibroadenoma

doesn´t increase the risk of breast cancer therapy:

- conservative: follow-up every 6 month

- radical: surgical extirpation italian study: extirpation leads to RR=2,0

(only follow-up) RR=0,97

2. Cysts

one of the most common changes from the lobular acini proliferation of the stromal component leads to an increased density of the gland therapy: conservative or punction of the

cyst

3a. Fibrocystic changes

present at 50-90% of women between 35-50 years of age, often asymptomatic

dysproportion of the involution - decrease of the amount of the stromal component (dominance of epithelial component)

histopathologic finding: fibrosis, cysts, adenosis, lymfoid infiltration, periductal inflammation

3b. Fibrocystic changes

intensity of „mastopatic“ changes which doesn´t correlate with the intensity of complaints

belongs to non-proliferative lesions of the breast zero proliferation indexes lead to worse mammographic lucidity therapy: conservative

4a. Papiloma

from the main ductus serose or bloody secretion from the nipple therapy: extirpation

4b. Juvenile papilomatosis

young women (under 20 years) solid, palpable formation (2-3cm) often upper outer quadrant multicystic

4c. Multifocal papilomatosis

from TDLU combination of epithelial and cystic

changes precancerosis therapy: extirpation, dispensarisation

5. Cystosarcoma phylloides

phyloides tumor proliferation of stromal component histologicaly commemorates intracanalicular

fibroadenoma often metaplasy: bone therapy: extirpation, often relaps

6. Rare tumours

lipoma adenolipoma myoepitelioma desmoidal tumour

7. Inflammation

juvenile hypertrophy - stromal hyperplasy duktektasis - dilatation of the large ductus

in perimenopausis or menopausis mechanical obstruction (deficiency of vit. A) cyklic mastodynie, palp. lesion, inflammation signs

therapy: symptomatic, ATB, excision

subareolar absces - chronic fistula therapy: incision, drainage, ATB

fat necrosis - trauma, radiotherapy, surgery

V. Carcinoma in situ

A) Ductal carcinoma in situ

– DCIS

B) Lobular carcinoma in situ

– LCIS

RR amplified 8-10x

A) Ductal carcinoma in situ

ductal epithelium has been replaced by carcinoma cells which doesn´t penetrate the basal membrane

often recidives in the place of biopsy microcalcifications often present therapy: extirpation + radioterapy or simple

mastectomy

B) Lobular carcinoma in situ

few clinical features no microcalcifications in 15-45% bilateral recidives bilateral LCIS – high risk

VI. Invasive breast carcinoma

1. Histologic type

2. Staging

3. Prognosis

4. Risk factors

5. Kancerogenesis

6. Characteristics of the tumour cell

7. Therapy

VI. Invasive breast carcinoma

1. Histologic type

2. Staging

3. Prognosis

4. Risk factors

5. Cancerogenesis

6. Characteristics of the tumour cell

7. Therapy

1a. Histologic type ductal carcinoma: 70-80% intraductal c.- type of DCIS lobular carcinoma - 10 % - difficult to detect by

mammography (no calcifications) medullar carcinoma - up to 5% - good

prognosis, doesn´t involve lymph nodes mucinous - coloid carcinoma - 3% - very slow

growth papilar carcinoma - 1% - bloody secretion

1b. Histologic type - special ca

inflammatory carcinoma – 1-4%, erythema, increased temperature, surgical treatment contraindicated,

primary treatment: radiotherapy Paget´s disease (carcinoma) – 4-5%, erosive

lesion of the nipple

VI. Invasive breast carcinoma

1. Histologic type

2. Staging

3. Prognosis

4. Risk factors

5. Cancerogenesis

6. Characteristics of the tumour cell

7. Therapy

2. Staging

T1 – tumour < 2 cm

T2 – tumour 2-5 cm

T3 – tumour over 5cm

T4 – penetration of the tumour into the chest

N1 – isolated metastasis, moveable l. nodes

N2 – isolated metastasis, fixated l. nodes

N3 – metastasis in internal mammary l. nodes

M1 – distant metastasis

Brain +

Skin +

Lung + + +

Pleura + + +

Liver + +

Adrenals + +

Bone + + + +

2. Staging - metastasis

VI. Invasive breast carcinoma

1. Histologic type

2. Staging

3. Prognosis

4. Risk factors

5. Cancerogenesis

6. Characteristics of the tumour cell

7. Therapy

3. Prognosis

smaller than 1 cm: survival rate 90-95% tumor 2-3 cm: survival rate 65% involvement of 1-3 LN: survival rate 62% involvment of more than 4 LN: survival rate 32% positivity of estrogen/progesterone receptors EGF receptor – worse grade, lymfatic invasion

VI. Invasive breast carcinoma

1. Histologic type

2. Staging

3. Prognosis

4. Risk factors

5. Cancerogenesis

6. Characteristics of the tumour cell

7. Therapy

4a. Risk factors

Breast cancer development probabilty in next 10 years in the relation with age

age risk

20 1 z 2000

30 1 z 256

40 1 z 67

50 1 z 39

60 1 z 29

Cancer Commitee of the College of American Pathologists, 1998

4b. Risk factors

sex - frequency of ca female x male: 135 : 1 age - 65 years over 30 years: RR 17 absolute risk in 50 years: 7-10% menarche – early onset: RR 2 first delivery – delivery after 20. year: RR 2-3 menopausis – late menopausis: RR 2 breast feeding over 1 year reduces the risk by

20%

4c. Risk factors

FH - 1.line: RR 2 - 3

- 2.line: RR do 1,5 genetic carcinoma breast/ovary (BRCA 1,2)

- tumour supresor gen, AD heriditary

- absolute risk: 85% life style, body weight – alcohol, obesity

(BMI > 35), hyperinsulinemie

4d. Risk factors

environment – chemical cancerogens, genotoxic substances

society status: high socioeconomic standart, stress

radiation drugs- prolactine agonists HRT - slight elevation by the use over 10 years

(kontroversy) 

4e. Epidemiology

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1970 1975 1980 1985 1990 1995 1997 1998

Incidence Mortalita

incidence: 90/100 000, mortality: 35/100 000incidence: 90/100 000, mortality: 35/100 000

4f. Epidemiology

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SRN Šv UK Fr It Šp USA Jap Alžír ČR

Incidence Mortalita

VI. Invasive breast carcinoma

1. Histologic type

2. Staging

3. Prognosis

4. Risk factors

5. Cancerogenesis

6. Characteristics of the tumour cell

7. Therapy

5. Cancerogenesis

oncogene activation genetics: genes BRCA 1,2, p53

1. Iniciation: during menarche - first delivery cancerogenes, radiation, nutrition, endogenous hormones2. Promotion: premenopausis (hormones)

postmenopausis - failure of apoptosis, failure of control of the cell cycle 

5. Cancerogenesis

10 20 30 40 50

carcinomaBRCA BRCA

1. delivery 1. delivery lifestyle lifestyle

INDUCTIONINDUCTIONCancerogensCancerogensRadiationRadiationHormonesHormones

MenarcheMenarche

PROMOTIONPROMOTIONHormonesHormonesGrowth factorsGrowth factors

defekty apoptozy,defekty apoptozy, antioxydační ochrany,antioxydační ochrany, opravy DNAopravy DNA

accumultaion of defect DNAaccumultaion of defect DNA

VI. Invasive breast carcinoma

1. Histologic type

2. Staging

3. Prognosis

4. Risk factors

5. Cancerogenesis

6. Characteristics of the tumour cell

7. Therapy

6. Characteristics of tumour cell

no control of proliferation loss of intercell adhesion loss of epithelium-stromal interaction (loss of

contact inhibition of growth) loss of diferenciation elevated metabolic activity changes of HR, abnormal reaction to hormones

VI. Invasive breast carcinoma

1. Histologic type

2. Staging

3. Prognosis

4. Risk factors

5. Cancerogenesis

6. Characteristics of the tumour cell

7. Therapy

7a. Therapy

survival rate is given by the stage radiotherapy reduces the incidency of loco-regional metastasis

lymphadenectomy decreases the frequency of

local recidives in cases of negative lymph node negativity

lymphadenectomy is only staging

7b. Therapy - surgery

radical mastectomy

(Halstead) quadrantectomy segmentectomy tumorectomy/WLE modified radical mastectomy subcutaneous mastectomy plastic operations

7c. Therapy - surgery

primary surgery: tumors of stage I, II

(size < 5 cm) standard therapy: modified radical mastectomy

(mastectomy, ALND I, II) lymphatic mapping: sentinel lymph node axillary lymphadenectomy is being still

indicated by invasive breast cancer

7c. Therapy - SLNM

patent blue

Tc scintigraphy

7d. Therapy - surgery

Breast conserving surgery: 1977 -

B. Fisher, J.L. Hayward, U.Veronesi condition:

- tumour size 3 – 4 cm

- tumour is not located in the breast center

- tumour is not multifocal

- radiotherapy must follow

7e. Therapy - plastic operations

7f. Therapy - plastic operations

7g. Algorithm in non-palpable l.Diagnosis of non-palpable l. (MG, US)

benign normal follow-up

probably benign check-up in 6 month

suspitious larger lesion localisation + biopsy benign

smaller lesion localisation+exstirpation benign

(core-cut, FNA)

+ peroperative histology

malignant

operation of malignancy according to surgico-oncological standards

7h. Radiotherapy

I: T2, over 4 positive LN intensity of radiation: 4-6 MV - linear acc. after conservative surgery - dose of 50 Gy

(5 weeks + boost 10-15 Gy – Ir192) radiotherapy of the scar, axilla paliative radiotherapy of metastasis

7h. Radiotherapy

7i. System therapy - chemot.

only systemic therapy can improve prognosis combined chemotherapy

- neoadjuvant – before surgery

- adjuvant – after the surgery CMF, FAC, AT, ET cyklofosfamid, 5-fluoruracil, metotrexate,

doxorubicin, epidoxorubicin

7j.System therapy - hormonal t.

estrogen receptor blockage

- antiestrogens - tamoxifen, raloxifen synthesis blockage

- aromatase inhibitor - arimidex high dose progesterones - down regulation

of estrogen and progesterone receptors ovarian ablation

surgical/radiotherapeutical

7k. Prevention

proper nutrition and life style: age of the first delivery – breast feeding

reduction of environmental risk factors (ionisation radiation, cancerogenes, alcohol)

early diagnosis and adequate therapy (system) chemoprevention - antiestrogens: Tamoxifen

(USA,UK, Itálie)

7k. Phytoestrogens

isoflavonids (Genistein): soja, tofu, kari, beer, bourbon

flavonoids (Galanin): tea leafs lignands (Indol-3-Carbinol): spinach, broccoli monoterpens (limonen): lemon karotenoids: (lutein, lycopen): tomatoes 

Edwin Smith - 3000-2500 pnl

If thou eaxminest a man having bulging tumors of his breast(and) thou findest that (swelling) have spread over his breast;if thou puttest thy hand upon his breast upon these tumors,(and) thou findest them very cool, there being no fever a alltherein when thy hand touches him: they have no granulation,they form no fluid, they do not generate secretion of fluid,and they are bulging to thy hand.There is no ( treatment).

Thank You for Your attention