Breast Cancer PDF

# Breast Cancer ## I. Basic Principles * **Most common carcinoma in women by incidence (excluding skin cancer)** * **2nd most common cause of cancer mortality in women** * **Risk factors are mostly related to estrogen exposure.** * **Female gender** * **Age** - Cancer usually arises in pos...

# Breast Cancer ## I. Basic Principles * **Most common carcinoma in women by incidence (excluding skin cancer)** * **2nd most common cause of cancer mortality in women** * **Risk factors are mostly related to estrogen exposure.** * **Female gender** * **Age** - Cancer usually arises in postmenopausal women, with the notable exception of hereditary breast cancer. * **Early menarche/late menopause** * **Obesity** * **Atypical hyperplasia** * **First-degree relative** (mother, sister, or daughter) with breast cancer ## II. Ductal Carcinoma in Situ (DCIS) * **Malignant proliferation of cells in the ducts with no invasion of the basement membrane** * **Often detected as calcification on mammography; DCIS does not usually produce a mass.** * Mammographic calcifications can also be associated with benign conditions such as fibrocystic changes (especially sclerosing adenosis) and fat necrosis. * Biopsy of calcifications is often necessary to distinguish between benign and malignant conditions. * **Histologic subtypes are based on architecture; comedo type is characterized by high-grade cells with necrosis and dystrophic calcification in the center of the ducts** * **Paget disease of the breast is DCIS that extends up the ducts to involve the skin of the nipple** * Presents as nipple ulceration and erythema. * Paget disease of the breast is almost always associated with an underlying carcinoma. ## III. Invasive Ductal Carcinoma * **Invasive carcinoma that classically forms duct-like structures** * **Most common type of invasive carcinoma in the breast, accounting for >80% of cases** * **Presents as a mass detected by physical exam or by mammography** * Clinically detected masses are usually 2 cm or greater. * Mammographically detected masses are usually 1 cm or greater. * Advanced tumors may result in dimpling of the skin or retraction of the nipple. * **Biopsy usually shows duct-like structures in a desmoplastic stroma; special subtypes of invasive ductal carcinoma include** * **Tubular carcinoma** - characterized by well-differentiated tubules that lack myoepithelial cells; relatively good prognosis * Tends to occur in older women (average age is 70 years) * Relatively good prognosis * **Medullary carcinoma** - characterized by large, high-grade cells growing in sheets with associated lymphocytes and plasma cells * Grows as a well-circumscribed mass that can mimic fibroadenoma on mammography * Relatively good prognosis * Increased incidence in BRCA1 carriers * **Inflammatory carcinoma** - characterized by carcinoma in dermal lymphatics * Presents classically as an inflamed, swollen breast (tumor cells block drainage of lymphatics) with no discrete mass; can be mistaken for acute mastitis * Poor prognosis ## IV. Lobular Carcinoma In Situ (LCIS) * **Malignant proliferation of cells in lobules with no invasion of the basement membrane** * **LCIS does not produce a mass or calcifications and is usually discovered incidentally on biopsy.** * **Characterized by dyscohesive cells lacking E-cadherin adhesion protein** * **Often multifocal and bilateral** * **Treatment is tamoxifen (to reduce the risk of subsequent carcinoma) and close follow-up; low risk of progression invasive carcinoma** ## V. Invasive Lobular Carcinoma * **Invasive carcinoma that characteristically grows in a single-file pattern; cells may exhibit signet-ring morphology.** * No duct formation due to lack of E-cadherin. ## VI. Prognostic and Predictive Factors * **Prognosis in breast cancer is based on TNM staging.** * **Metastasis** is the most important factor, but most patients present before metastasis occurs. * **Spread to axillary lymph nodes** is the most useful prognostic factor (given that metastasis is not common at presentation); sentinel lymph node biopsy is used to assess axillary lymph nodes. * **Predictive factors predict response to treatment.** * **Most important factors** are estrogen receptor (ER), progesterone receptor (PR), and HER2/neu gene amplification (overexpression) status. * **Presence of ER and PR** is associated with response to antiestrogenic agents (e.g., tamoxifen); both receptors are located in the nucleus. * **HER2/neu amplification** is associated with response to trastuzumab (Herceptin), a designer antibody directed against the HER2 receptor; HER2/neu is a growth factor receptor present on the cell surface. * **'Triple-negative' tumors** are negative for ER, PR, and HER2/neu and have a poor prognosis; African American women have an increased propensity to develop triple-negative carcinoma. ## VII. Hereditary Breast Cancer * **Represents 10% of breast cancer cases** * **Clinical features that suggest hereditary breast cancer include multiple first-degree relatives with breast cancer, tumor at an early age (premenopausal), and multiple tumors in a single patient.** * **BRCA1 and BRCA2 mutations are the most important single gene mutations associated with hereditary breast cancer.** * **BRCA1 mutation** is associated with breast and ovarian carcinoma. * **BRCA2 mutation** is associated with breast carcinoma in males. * **Women with a genetic propensity to develop breast cancer may choose to undergo removal of both breasts (bilateral mastectomy) to decrease the risk of developing carcinoma.** * A small risk for cancer remains because breast tissue sometimes extends into the axilla or subcutaneous tissue of the chest wall. ## VIII. Male Breast Cancer * **Breast cancer is rare in males (represents 1% of all breast cancers).** * **Usually presents as a subareolar mass in older males** * Highest density of breast tissue in males is underneath the nipple. * May produce nipple discharge. * **Most common histological subtype is invasive ductal carcinoma.** * Lobular carcinoma is rare (the male breast develops very few lobules). * **Associated with BRCA2 mutations and Klinefelter syndrome**