22.

Female Breast
 The Breast

Breast

Normal

Pathology

Developmental
Anomalies Clinical features

Benign Epithelial
Inflammations
lesions

Carcinoma Male Breast

 Breast Carcinoma

Arise from epithelial cells,

one in nine women develops breast cancer during her life-time (1/3 fatal);
Risk Factors-
1. strong family history first-degree relatives with cancer,
2. Specific genes linked to genetic inheritance , p53 -Li-Fraumeni syndrome, ATM -ataxia-
telangiectasia; BRCA1 and 2 (Genetic inheritance is in < 10% of all breast cancer cases)
3. ↑ age (rare <25 except if familial, average diagnosis is at 64);
4. preexisting proliferative breast disease (particularly atypical Hyperplasia);
5. Ca. of the contra lateral breast and Ca. endometrium;
6. Radiation exposure at a young age
7. Early menarche and late menarche;
8. Nulliparous women (unremitting exposure to the ovarian cycle);
9. Women having their first child after 30;
10. Obese postmenopausal women (increased synthesis of estrogens in fat deposits);
11. Cellular changes; increased expression of oncogenes (ex. c-erb-B2, INT2, c-ras, c-myc),
decreased expression or function of tumor-suppressor genes (ex. NM23, p53, RB),
alterations in cell structure (ex. increased expression of vimentin, decreased expression of
fodrin), loss of cell adhesion (ex. E-cadherin, integrins), increased expression of cell cycle
proteins (ex. cyclins, Ki-67, proliferating cell nuclear antigen), increased expression of
angiogenic factors (ex. VEGF, FGF) increased expression of proteases (ex. cathepsin D,
stromelysins);
12. Site- 50% - upper outer quadrant;
 Breast Carcinoma

Classified as: in situ (noninvasive) - 15 to 30% of all cancers: can be ( DCIS
(intraductal carcinoma), LCIS (lobular carcinoma);

invasive (invasive) – MC is invasive ductal carcinoma (80%)

Ductal carcinoma in situ (DCIS) - proliferations of tumor cells within ducts and lobules
confined by the basement membrane, spread from lactiferous ducts into the contiguous skin of
the nipple - Paget disease of the nipple (nipple -eczematous or ulcerated, not detected on the
mammogram; 1/3 can develop carcinoma over time if untreated;

Lobular carcinoma in situ- proliferation of small, uniform cells within ducts and lobules that
fill, distend or distort at least 50% of the acinar units of a single lobule; always an incidental
finding ,never forms a mass , calcifications are rare, invasive carcinoma develops in 25 to 30%
of women with LCIS in contrast to DCIS, both breasts are at equal risk,

Invasive ductal carcinoma (IDC) MC type - or cannot be classified or no special type
(NST); malignant cells with a dense stromal reaction hard consistency (scirrhous carcinoma)

Invasive Lobular Ca.-5 to 10% of invasive carcinomas, multifocal and bilateral diffusely
invasive - difficult to detect clinically and mammographically; composed of small, uniform
cells forming strands of infiltrating tumor cells, sometimes arranged concentrically about ducts
(bull's eye lesions); Behavior- frequently metastasize to CSF (carcinomatous meningitis),
serosal surfaces, ovary and uterus, bone marrow

Medullary carcinoma - younger age; with BRCA1 mutations ; Grossly- large, soft, well
circumscribed ; no desmoplasia, a moderately dense lymphoblastic infiltrate,

Others- Colloid (mucinous) ca. Tubular (cribriform) ca. Papillary carcinoma - have
good prognosis
Paget disease
 Lobular carcinoma

Lobular carcinoma in situ Invasive Lobular carcinoma

 Breast carcinoma

Excess stromal proliferation. Desmoplasia

Medullary carcinoma
Colloid (mucinous) carcinoma
 Stromal Tumors

1. Fibroadenoma (Br. Mouse) - MC benign tumor of the female breast, during the
reproductive period; cyclosporine A therapy; Clinically- well circumscribed
palpable masses or mammographic densities, (during pregnancy- grow in size and
sometimes infarct), in older women- calcify, Benign & associated with proliferative
changes; slightly increased risk of cancer; Grossly-solitary white, rubbery nodules
from 1 to 10 cm in diameter; Histologically -biphasic (stroma and epithelium
lining cystic spaces)

2. Phyllodes tumors - similar to fibroadenomas; but seen as palpable masses in

women 50 – 70 yrs. (10 to 20 years older than fibroadenomas) & ↑cellularity,
mitotic activity, stromal overgrowth and invasiveness Behavior-Most - benign &
cured by local excision, few recur; few are highly malignant

3. Sarcomas -rare, can leiomyo, chondros and osteosarcoma; Sarcomatous

differentiation in phyllodes tumors and carcinomas -metaplastic carcinomas;
Lymphangio-sarcomas if arise after radiation therapy for breast cancer or skin of a
chronically edematous arm in a post- mastectomy patient- Stewart-Treves
syndrome
Fibroadenoma (Br. MOUSE)
 Mammographic Changes

1. Densities - most Neoplasms - radiologically denser than the intermingled

connective and adipose tissue of the normal breast; Invasive carcinomas-
spiculated density with irregular borders ; Benign lesions - well-circumscribed
densities with smooth borders

2. Calcifications - DCIS is the MC malignancy associated with calcifications;

malignancy - small, irregular, numerous and clustered or linear and branching,

3. Changes over time -Relentless growth of malignancies may be seen by

comparison of sequential mammograms for developing densities, architectural
distortion or increased in the number of calcifications

4. Limitations of Mammography-some carcinomas (even if palpable) may not be

detected by mammography due to surrounding dense stroma (esp. in younger
women), absence of calcification, small size, close to the chest wall in the
periphery of the breast
Mammogram of Young Beast
Mammogram of aged Beast
Multiple small Irregular clusters

Cause?
Large density With Irregular Border

Cause ?
 Features common to all invasive carcinomas

• Local invasion into adjacent structures produces tissue fixation, retraction of the
nipple and dimpling of the skin,

• Extensive lymphatic blockage by tumor can result in Lymphedema, causing the

breast skin to resemble an orange peal (peau d'orange)

• Inflammatory carcinomas present as a markedly enlarged erythematous and

swollen breast, inflammation is absent

• 1/3rd of breast carcinomas present with lymph node metastases, can metastasize to
axillary, supraclavicular or internal mammary nodes (tumors of outer quadrant -
metastasize to axillary nodes, of inner quadrants and center to internal mammary
nodes)
 Prognostic indicators in Breast carcinomas
• Tumor size; larger the tumor the worse the prognosis
• Locally advanced disease; locally advanced disease (invasion into
skin or chest wall) - poor prognosis,
• lymph node metastases; Lymph node metastases -most important
prognostic factor, ( no involvement, 10 year survival - 70 to 80%,
if 10 are involved it is 10 to 15%);
• distant metastases;
• all special subtypes have a better prognosis when compared to NST
cancers, (tubular and colloid ca. - best prognosis),
• Poorly differentiated ca. - worse prognosis;
• carcinomas with hormone receptors have a slightly better prognosis
(Rx. with less toxic hormonal therapies);
• Lymphovascular invasion - poor prognostic ;
• involvement of dermal lymphatics (inflammatory carcinoma) –poor
prognosis
 Prognostic indicators in Breast carcinomas
• Tumor size; larger the tumor the worse the prognosis
• Locally advanced disease; locally advanced disease (invasion into
skin or chest wall) - poor prognosis,
• lymph node metastases; Lymph node metastases -most important
prognostic factor, ( no involvement, 10 year survival - 70 to 80%,
if 10 are involved it is 10 to 15%);
• distant metastases;
• all special subtypes have a better prognosis when compared to NST
cancers, (tubular and colloid ca. - best prognosis),
• Poorly differentiated ca. - worse prognosis;
• carcinomas with hormone receptors have a slightly better prognosis
(Rx. with less toxic hormonal therapies);
• Lymphovascular invasion - poor prognostic ;
• involvement of dermal lymphatics (inflammatory carcinoma) –poor
prognosis
• Breast carcinomas contd….

• Poor prognostic indicators; - Increased angiogenesis, DNA content if abnormal,

increased levels of proliferation markers, expression of Oncogenes (ex. c-erb-B2)
and loss of expression of tumor-suppressor genes, proteases

• Current therapy includes -local and regional control using combinations of

surgery (mastectomy or breast conservation - lumpectomy) and postoperative
radiation and systemic control using hormonal treatment, chemotherapy or both,
newer strategies include inhibition (by pharmacologic agents or specific antibodies)
of membrane-bound growth receptors (ex. c-erb-B2), stromal proteases,
angiogenesis

• Cytological features of malignancy  Hyperchromatic nuclei – dark staining, ↑ in

DNA content, ↑ N: C ratios – large nucleoli, Irregular nuclear membrane, Atypical
mitosis, Pleomorphic – large and small cells  all mixed & not producing any
recognizable pattern
 Male breast-

• Gynecomastia - enlargement of the male breast, key indicator -

imbalance between estrogens and androgens, (during puberty, in
Klinfelter's syndrome, manifestation of hormone-producing tumors -
ex. Leydig cell or Sertoli cell tumors) ; Cirrhosis; side effect of drugs
(ex. marijuana, anabolic steroids, some psychoactive agents);
Histologically - proliferation of both epithelial and stromal
components,

• Carcinoma of the male breast -risk factors, prognostic factors are

similar to those of women, male breast cancer is strongly associated
with BRCA2 in some families the same histological types of breast
cancer are found in men and women, because the scant amount of
surrounding breast tissue in men, carcinomas tend to invade the skin
and chest wall earlier and present at higher stages
 Carcinoma of Breast
Cytological features of malignancy

• Hyperchromatic nuclei –
dark staining
• ↑ in DNA content
• ↑ N:C ratios – large
nucleoli
• Irregular nuclear
membrane
• Atypical mitosis
• Pleomorphic – large and
small cells  all mixed in
• Not producing any
recognizable pattern
 The Breast – Pathology
Carcinoma of Breast

Lymphangiosarcoma Breast cancer

ST syndrome

Huge breast cancer

Metastasis in her axilla is almost as big as the
breast cancer
Died within a few days of the picture
Gynecomastia