Breast Cancer

Basics

Description

  • Breast cancer is a malignant neoplasm of breast epithelial, glandular, or stromal cells.
  • Histologic subtypes
    • Noninvasive
      • Ductal carcinoma in situ: confined to ducts; may show mammographic microcalcifications; high risk for ipsilateral invasive carcinoma
      • Lobular carcinoma in situ: confined to terminal ductal lobular units; low risk for ipsilateral/contralateral invasive carcinoma
    • Invasive
      • Invasive ductal carcinoma: 70–80% of cases; unilateral; cords/nests of cells
      • Invasive lobular carcinoma: 8% of cases; bilateral 20% of the time; single-file stromal infiltration
      • Inflammatory breast cancer: rare; dermal lymphatic invasion; peau d’orange
    • Paget disease: rare; nipple/areolar involvement; red/scaly rash, pruritus, ulceration, nipple retraction, discharge
  • Molecular subtypes (receptor-defined)
    • Hormone receptor positive (HR+): estrogen receptor (ER) and/or progesterone receptor (PR)
    • Human epidermal growth factor receptor 2 (HER2) status is determined by immunohistochemistry (IHC) and confirmed by fluorescence in situ hybridization (FISH):
      • Negative (0): no HER2 expression (IHC 0, FISH−)
      • Ultralow: minimal expression (IHC ≤10% faint staining, FISH−)
      • Low: low expression (IHC 1+ or 2+, FISH−)
      • Positive: overexpression (IHC 3+ or 2+ with FISH+)
    • No ER, PR, HER2 expression (triple negative)

Epidemiology

Incidence

  • 2018 to 2022: U.S. incidence was 130.8/100,000 women/year.
  • Median age: 63 years
  • Rates increased by 0.6%/year from 2013 to 2022
  • Highest rates in North America, Australia/New Zealand, Western/Northern Europe

Prevalence

  • Most diagnosed cancer worldwide
  • Second most common malignancy in women after non-melanoma skin cancers
  • ~4 million U.S. women lived with breast cancer in 2022.
  • Lifetime risk for women (2018 to 2021) is ~13%.
  • 15.5% of all new cancer cases in the United States

Etiology and Pathophysiology

  • Etiology: increased hormone exposure, genetic mutations, lifestyle/environmental factors
  • Arises from uncontrolled proliferation of mammary epithelial cells, starting as ductal/lobular carcinoma in situ, progressing to invasive carcinoma with stromal infiltration, and spreading via lymphatics/blood to distant sites

Genetics

  • 5–10% of breast cancers are hereditary.
  • Tumor suppressor genes:
    • BRCA1 and BRCA2: autosomal dominant DNA repair defects; seen in male breast cancer
    • Other: TP53, PTEN, CHEK2, PALB2
  • Oncogenes: HER2 receptor expression, PIK3CA and ESR1 mutations

Risk Factors

  • Characteristics: female sex, age >65 years, postmenopausal, dense breasts, obesity
  • Genetic: BRCA or other mutations, first-degree relative with breast cancer
  • Prolonged estrogen exposure: early menarche, late menopause, nulliparity, late first pregnancy, lack of breastfeeding, hormone replacement therapy, oral contraceptives
  • Lifestyle/environmental: alcohol, smoking, high-fat diet, prior chest radiation

General Prevention

  • Early detection in average-risk women: biennial mammogram from age 40 to 74 per U.S. Preventative Services Task Force (1)
  • Family history: screening 10 years before earliest family diagnosis (but not before age 30 years)
  • High-risk women (≥20% lifetime risk): annual MRI + mammogram starting age 30 years
  • Transgender individuals
    • Trans men: no screening after bilateral mastectomy; otherwise, follow cisgender guidelines.
    • Trans women: if ≥5 years of hormone therapy, screen as cisgender women; if <5 years, screening based on risk factors
  • Risk-reducing interventions for BRCA or other high risk gene carriers:
    • Prophylactic bilateral mastectomy ± salpingo-oophorectomy
    • Chemoprevention (5 year duration):
      • Premenopausal and age ≥35 years: selective ER modulator (tamoxifen)
      • Postmenopausal: selective ER modulators (tamoxifen, raloxifene) or aromatase inhibitors (anastrozole, letrozole, exemestane)

Commonly Associated Conditions

Breast, ovarian, prostate, and pancreatic cancer in BRCA+ patients

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