16 Breast Cancer
Epidemiology
Breast cancer is the most frequent cancer in women and the second most frequent cause of cancer death in women. It is more frequent in industrialized nations than in developing ones, but the rates in the former are decreasing likely due to screening and the rates in the latter are rising.
Pathology
Breast cancer usually arises in the terminal duct lobule. It is classified by light microscopy as either lobular or ductal. The most common type is invasive or infiltrating ductal carcinoma (70–80%). The remaining 20 to 30% are subtypes that must represent at least 90% of the tumor. 1
Genetics
Familial breast cancer comprises 20 to 30% of all breast cancers. BRCA1 and BRCA2 are the two genes associated with familial breast and ovarian cancer syndrome, which is about half of all inherited breast cancers. About 70 to 80% of breast cancer is sporadic and not associated with a particular genetic alteration. 2 , 3 If either BRCA1 or BRCA2 is present, there is a 60 to 85% lifetime risk of breast cancer and a 15 to 40% risk of ovarian cancer. The tumors associated with the BRCA1 or BRCA2 mutation are likely to be estrogen receptor (ER) and progesterone receptor negative (PR negative) and overexpress human epidermal growth factor receptor 2 (HER2).
Other hereditary syndromes include the following:
Li–Fraumeni syndrome = Breast cancer, soft-tissue sarcoma, CNS (central nervous system) tumors, adrenocortical cancer, leukemia, and prostate cancer. Risk of breast cancer is 50 to 90% by the age of 50 years. Genetic mutation is TP53 (tumor protein 53).
Cowden’s syndrome = Breast cancers, hamartoma, thyroid, oral mucosa, endometrial brain tumors. Risk of breast cancer is 25 to 50%. Genetic mutation is PTEN (phosphate and tensin homolog).
Familial diffuse gastric cancer = Lobular breast cancer, gastric cancer. Incidence of breast cancer is at least six times normal. Genetic mutation is CDH1 (cadherin-1).
Peutz–Jeghers syndrome = Breast, ovarian, testis, pancreas, cervix, uterine, colon cancers; melanocytic macules of lips and digits; gastrointestinal hamartomatous polyps. Breast cancer risk is 30 to 50% by the age of 70 years. Genetic mutation is STK11 (serine/ threonine kinase 11)/LKB1 (liver kinase B1). 4
Staging 5
Tumor
Tis = Tumor in situ.
T1 = Tumor is less than 2 cm in greatest dimension.
T2 = Tumor is between 2 and 5 cm in greatest dimension.
T3 = Tumor is greater than 5 cm in greatest dimension.
T4a = Extension to chest wall.
T4b = Ulceration or satellite nodules.
T4c = T4a + T4b.
T4d = Inflammatory carcinoma.
Lymph Nodes
N0 = No lymph node metastases.
N1 = Levels I, II moveable ipsilateral positive nodes in axilla.
N1mi = Microscopic metastases, less than 1 mm in greatest dimension.
N2a = Fixed levels I, II ipsilateral axillary nodes.
N2b = Clinically detected nodes in the ipsilateral internal mammary chain without axillary nodal involvement.
N3a = Metastases in ipsilateral infraclavicular nodes.
N3b = Metastases in ipsilateral internal mammary chain and in axilla.
N3c = Metastases in ipsilateral supraclavicular nodes.
Metastases
M0 = No distant metastases.
M1 = Distant metastases present.
Stages
Stage 0 = Tis N0 M0.
Stage IA = T1 N0 M0.
Stage IB = T0 N1mi M0 or T1 N1mi M0.
Stage IIA = T0 N1 M0 or T1 N1 M0 or T2 N0 M0.
Stage IIB = T2 N1 M0 or T3 N0 M0.
Stage IIIA = T0 N2 M0 or T1 N2 M0 or T2 N2 M0 or T3 N1 M0 or
T3 N1 M0 or T3 N2 M0.
Stage IIIB = T4 N0 M0 or T4 N1 M0 or T4 N2 M0.
Stage IIIC = Any T N3 M0.
Stage IV = Ant T, Any N, M1.
While TNM (tumor size, node involvement, and metastasis status) staging has been important in the determination of prognosis, the genetic analysis of the tumors not only has led to more targeted therapies, but also has been utilized for prognosis.
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