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Breast Cancer for USMLE Step 3

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Breast Cancer for the USMLE Step 3 Exam
Definition and Classification
  • Definition
    • Breast cancer is a malignancy originating from breast tissue, most commonly from the ducts (ductal carcinoma) or lobules (lobular carcinoma).
  • Classification by Receptor Status
    • Hormone Receptor-Positive (ER+ and/or PR+): Comprises around 70% of breast cancers; responsive to hormone therapy.
    • HER2-Positive: Characterized by overexpression of the HER2 protein, associated with a more aggressive course but responsive to HER2-targeted therapies.
    • Triple-Negative Breast Cancer (TNBC): Lacks ER, PR, and HER2 receptors; associated with a poorer prognosis and treated with chemotherapy.
Epidemiology and Risk Factors
  • Epidemiology
    • Breast cancer is the most common cancer in women and the second leading cause of cancer-related deaths among women.
  • Risk Factors
    • Non-Modifiable: Female gender, increasing age, family history, BRCA1/2 mutations, early menarche, and late menopause.
    • Modifiable: Obesity, alcohol use, hormone replacement therapy, lack of physical activity, and nulliparity.
Pathophysiology
  • Genetic Mutations
    • BRCA1 and BRCA2: Germline mutations linked to high risks of early-onset breast and ovarian cancers.
    • Additional Mutations: Genes like p53, PTEN, and CHEK2 are associated with sporadic cases.
  • Hormonal Influence
    • Estrogen and progesterone promote breast epithelial cell proliferation, especially in ER-positive cancers.
Clinical Manifestations
  • Palpable Mass
    • Most common symptom; typically a firm, painless mass with irregular borders.
  • Skin and Nipple Changes
    • Skin dimpling, nipple retraction, and discharge (often bloody) can occur in advanced disease.
    • Inflammatory breast cancer presents with erythema, edema, and peau d’orange (skin thickening).
  • Axillary Lymphadenopathy
    • Enlarged axillary nodes may indicate regional metastasis.
breast cancer breast changes
Screening
  • Guidelines
    • Mammography every two years is recommended for average-risk women aged 40-74 by the USPSTF.
  • Breast MRI
    • Used as an adjunct for high-risk populations, such as BRCA mutation carriers, along with mammography for annual screening.
Diagnosis
  • Imaging
    • Diagnostic Mammogram: Used for detailed assessment of abnormal screening findings.
    • Ultrasound: Useful for evaluating characteristics of a mass and assessing axillary nodes.
  • Biopsy
    • Core Needle Biopsy: Preferred method for obtaining tissue, allowing for histopathologic analysis and receptor status testing.
    • Fine-Needle Aspiration (FNA): May be performed for palpable masses but lacks adequate tissue for full receptor profiling.
Staging
  • TNM System
    • Staging is based on tumor size (T), lymph node involvement (N), and distant metastasis (M), with stages ranging from 0 (in situ) to IV (metastatic disease).
  • Prognostic Factors
    • Tumor grade, hormone receptor status (ER/PR), HER2 expression, lymph node involvement, and size are essential for guiding treatment and prognosis.
Treatment
  • Surgery
    • Lumpectomy (Breast-Conserving Surgery): Tumor excision with surrounding margin, usually followed by radiation.
    • Mastectomy: Complete breast removal, preferred in larger or multicentric tumors.
    • Sentinel Lymph Node Biopsy (SLNB): Assesses regional lymph node involvement; if positive, may warrant axillary dissection.
  • Radiation Therapy
    • Typically administered after lumpectomy to decrease local recurrence, and selectively post-mastectomy based on risk factors.
  • Systemic Therapy
    • Hormonal Therapy: Used for ER/PR-positive tumors, including tamoxifen for premenopausal women and aromatase inhibitors for postmenopausal women.
    • Chemotherapy: Often used for high-risk cases, TNBC, and HER2-positive cancers.
    • HER2-Targeted Therapy: Trastuzumab and related agents improve outcomes in HER2-positive breast cancer.
Key Points
  • Breast Cancer is the most common malignancy in women, classified by receptor status to guide therapy and prognosis.
  • Risk Factors include both non-modifiable (age, gender, family history) and modifiable factors (obesity, alcohol, HRT).
  • Screening: Mammography is recommended every two years for women aged 40-74, with MRI added for high-risk groups.
  • Diagnosis: Includes clinical exam, imaging, and biopsy for histology and receptor status.
  • Staging: Follows the TNM system, with factors like hormone receptor and HER2 status guiding prognosis and treatment.
  • Treatment:
    • Surgery and radiation for local control.
    • Systemic therapies (hormonal, chemotherapy, HER2-targeted) are based on receptor status and tumor characteristics.

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