Breast Cancer

Pathophysiology of Breast Cancer

Breast cancer is a:

1) neoplastic transformation of glandular epithelium of the terminal duct unit, lactiferous proximal ducts, or lobules of the breast
2) almost always adenocarcinoma
3) classification is controversial, but most experts recognize in situ (malignant cells do not invade through the basement membrane) and invasive forms
4) in situ types – intraductal (comedo and noncomedo sutypes) in situ, lobular in situ, and papillary in situ
5) invasive types – ductal, lobular, tubular, colloid, and medullary

Signs and Symptoms

1) palpable mass – hard, irregular, no discrete margins, fixed to underlying tissue
2) nipple discharge
3) breast pain
4) retracted or puckered skin
5) skin erythema and edema owing to blocked lymphatics in skin (peau d’orange)
6) itchy, scaly, ezcema-type tissue on nipples (Paget’s disease)
7) palpable lymph nodes

Characteristic Test Findings

Radiology

mass or suspicious calcifications on mammogram

Histology/Gross Pathology

Comedo intraductal in situ

1) large, pleomorphic cells
2) distended ducts with necrotic material

Nocncomedo intraductal in situ

3) cells usually smaller than comedo
4) lacks necrotic material

Lobular in situ

5) often an incidental finding on breast biopsy
6) small cells with minute nucleoli
7) considered marker for high risk for subsequent invasive cancer

Invasive ductal

8) stromal invasion occurs with irregular nests and cords of epithelial cells
9) fibroblastic proliferation

Invasive lobular

10) marked by single strands of cells infiltrating stroma (“Indian filing” or “single-cell” pattern)

Associated Conditions:

increased incidence of breast cancer with

1) first-degree relative
2) Li-Fraumeni syndrome (owing to p53 mutation)
3) BRCA1 gene (17q21)
4) BRCA2 gene (13q)
5) early menarche
6) late menopause
7) older age at first pregnancy
8) nulliparity
9) previous breast cancer
10) smoking
11) alcohol
12) estrogen HRT during and after menopause

Biochemistry

1) estrogen and progesterone receptors (good prognosis)
2) measurements of increased proliferative capacity (poor prognosis) – mitotic index, S phase, ki 67, and her-2/neu

Inheritance/Epidemiology

1) most common malignancy in women in USA (1/9 will develop during lifetime)
2) colloid type typically occurs in older women
3) medullary and tubular types have relatively good prognoses
4) presence of lobular in situ carcinoma heralds a 30% risk of developing invasive carcinoma in next 20 years

Tips for USMLE

1) BRCA1 and BRCA2 predispose for breast and ovarian cancer in women
2) BRAC2 predisposes to breast cancer in men and Ashkenazi Jewish women
3) Li Fraumeni has increased risk of breast cancer, osteosarcoma, brain tumors, leukemia, adrenal cancer, and soft tissue sarcomas
4) Paget’s diease of the breast is an adenocarcinoma with itchy, scaly nipple
5) typically, palpable masses without mammogram findings are invasive lobular carcinoma