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Breast Cancer

Basics

  • Most common cancer in women and 2nd leading cause of cancer death in U.S. women
  • Types: DCIS, infiltrating ductal/lobular carcinoma, Paget disease, phyllodes tumor, inflammatory, angiosarcoma
  • Molecular subtypes: luminal A (ER+/PR+/HER2-), luminal B, triple negative, HER2-enriched

Epidemiology

  • ~297,790 new invasive cases and 55,720 DCIS cases in 2023 in U.S. women
  • ~43,700 deaths annually

  • 3.8 million breast cancer survivors in U.S.

Etiology and Pathophysiology

  • Mutations in BRCA1, BRCA2 tumor suppressor genes impair DNA repair
  • Estrogen/progesterone receptor signaling induces cyclin D1 and c-Myc, promoting proliferation
  • Cross-talk with EGFR family implicated in tumorigenesis
  • 5-10% hereditary breast cancers linked to genetic syndromes (BRCA, Cowden, Li-Fraumeni, others)

Risk Factors

  • Female sex, advanced age
  • Hormone replacement therapy (especially combined estrogen-progesterone)
  • Family history and genetic mutations
  • Early menarche, late menopause, nulliparity, late first pregnancy
  • Obesity, alcohol use, dense breasts, prior radiation exposure
  • History of proliferative breast disease

Prevention

  • Maintain healthy weight, limit alcohol to ≤1 serving/day
  • Vitamin D supplementation may reduce risk
  • USPSTF recommends risk-reducing meds (tamoxifen, raloxifene, aromatase inhibitors) in high-risk women
  • Breast self-exam no longer routinely recommended
  • Mammography: biennial starting at age 40 to 74 (USPSTF) or annual 45-54 then biennial or annual thereafter (ACS)

Diagnosis

History

  • Painless breast or axillary lump
  • Skin changes: dimpling, erythema, peau d'orange
  • Nipple discharge or retraction

Physical Exam

  • Visual inspection: asymmetry, skin changes
  • Palpation of all quadrants and regional lymph nodes

Differential Diagnosis

  • Fibrocystic changes, fibroadenoma
  • Intraductal papilloma, cyst, galactocele
  • Infection: abscess, mastitis
  • Fat necrosis, sclerosing adenosis
  • Breast carcinoma mimics

Diagnostic Tests

  • Mammography with BI-RADS classification guides further management
  • Ultrasound to distinguish cystic vs solid masses
  • Biopsy (FNA, core needle, stereotactic, MRI-guided) for definitive diagnosis
  • Imaging for staging in advanced disease: chest/abdomen CT, PET/CT, bone scan, MRI brain/spine if indicated
  • Pathology includes tumor type, size, grade, receptor status (ER, PR, HER2)

Treatment

Medication

  • Neoadjuvant chemotherapy for locally advanced, triple-negative, or HER2+ tumors
  • Cytotoxic agents: anthracyclines, taxanes, alkylating agents
  • Anti-HER2 therapy (trastuzumab ± pertuzumab) in HER2+ patients
  • Hormone therapy (tamoxifen, aromatase inhibitors) for ER+ tumors
  • Consider genetic counseling and fertility preservation

Surgery

  • Breast conserving surgery (lumpectomy) + radiation or mastectomy
  • Axillary node biopsy or dissection based on imaging and biopsy results

Radiation

  • Indicated after breast conservation therapy
  • Postmastectomy RT for large tumors or nodal involvement

Follow-Up

  • Every 4-6 months for 5 years, then annually
  • Annual mammogram 6-12 months post-treatment, then yearly
  • Monitor bone density during endocrine therapy
  • No routine tumor markers or imaging unless clinically indicated

Prognosis

  • 5-year survival: localized 99%, regional 86%, distant 30%
  • Modifiable risk factors: alcohol, BMI, inactivity
  • Recurrence risk related to stage and subtype

Complications

  • Surgery: lymphedema, infection, pain, limited mobility
  • Chemotherapy: immunosuppression, neuropathy, cardiotoxicity
  • Radiation: skin fibrosis, chronic pain, secondary malignancies
  • Endocrine therapy: osteoporosis, thromboembolism, endometrial cancer

Clinical Pearls

  • Normal mammogram does not exclude cancer in a palpable mass
  • Genetic testing guided by family history and tumor characteristics
  • Multidisciplinary care improves outcomes