Breast Cancer

Descriptive text is not available for this image BASICS

Most commonly diagnosed cancer (CA) in women and the second most common cause of CA death for U.S. women; females have a ~13% chance of developing breast cancer (BC) and a 2.5% chance of dying from BC if they develop the disease.

DESCRIPTION

  • Malignant neoplasm of cells native to the breast—epithelial, glandular, or stroma
  • Types: invasive (infiltrating ductal carcinoma, infiltrating lobular carcinoma) or noninvasive (ductal carcinoma in situ [DCIS])
  • Molecular subtypes: luminal A (ER+/PR+/HER2−), triple negative (ER−/PR−/HER2−), luminal B (ER+/HER−), luminal B-like (ER+/HER2+), HER2-enriched (ER−/PR−/HER2+)

EPIDEMIOLOGY

Incidence

Estimated in 2024: ~310,720 new cases of invasive BC, ~56,500 DCIS; ~42,250 deaths from BC in U.S. women; increased by ~0.5% per year since mid-2000s

Prevalence

>4 million BC survivors in the U.S. (1)

ETIOLOGY AND PATHOPHYSIOLOGY

Genes such as BRCA1 and BRCA2 function as tumor suppressor genes, and mutation leads to cell cycle progression and limitations in DNA repair. Mutations in estrogen/progesterone induce cyclin D1 and c-Myc expression, leading to cell cycle progression. Additional tumors (33%) may cross talk with estrogen receptors and epidermal growth factor receptors (EGFR), leading to similar abnormal cellular replication.

Genetics

  • Criteria for additional risk evaluation/gene testing in affected BC individual
    • BC at aged ≤50 years
    • BC at any age and
      • ≥1 family member with BC (≤50 years of age or in men) or ovarian/fallopian tube/primary peritoneal CA any age
      • ≥2 family members with BC or pancreatic CA any age
      • Population at increased risk (e.g., Ashkenazi Jewish descent)
    • Triple-negative BC (ER−, PR−, HER2−)
    • Second primary BC (not recurrence of first), ovarian/fallopian tube/primary peritoneal CA
    • ≥1 family member with BC and CA of thyroid, adrenal cortex, endometrium, pancreas, central nervous system, diffuse gastric, aggressive prostate (Gleason score of >7), leukemia, lymphoma, sarcoma, dermatologic manifestations, and/or macrocephaly, gastrointestinal (GI) hamartomas
    • Male BC
  • 5–10% of BCs are associated with genetic mutations and are thus hereditary.
    • BRCA1 and BRCA2 are inherited in an autosomal fashion and have increased risk of BC, ovarian CA, pancreatic CA, and possibly other CAs.
    • Syndromes associated with BC: Cowden syndrome (PTEN), Li-Fraumeni syndrome (TP53), ataxia-telangiectasia (ATM), and Peutz-Jeghers (STK11), hereditary diffuse gastric CA (CDH1); other BC genes include PALB2 and CHEK2.

RISK FACTORS

  • National Cancer Institute Breast Cancer Risk Assessment Calculator: https://bcrisktool.cancer.gov
  • Nonmodifiable risk factors
    • Female sex, aged >65 years, tall stature, dense breasts (>50%), Ashkenazi Jewish descent
    • Biopsy confirmed atypical hyperplasia, DCIS, lobular carcinoma in situ (LCIS)
    • Hereditary BC susceptibility genes
    • Personal or family history of BC at a younger age, history of endometrial or ovarian CA, history of radiation or diethylstilbestrol (DES) exposure (especially at a young age)
    • Hormonal factors: early menarche (<12 years of age), late menopause (>55 years of age), first pregnancy at >35 years of age, postmenopausal
  • Modifiable risk factors
    • Obesity
    • Alcohol use
    • Hormone replacement therapy (combination estrogen-progesterone and estrogen only agents [but not vaginal estrogen]) during perimenopause increases BC risk for 10 years after medication is discontinued.
    • Nulliparous, no history of full-term pregnancy or breastfeeding

GENERAL PREVENTION

  • Medication: United States Preventative Services Task Force (USPSTF) recommends that clinicians offer to prescribe risk-reducing medications, such as tamoxifen, raloxifene, or aromatase inhibitors (AIs), to women >35 years old who have a >3% risk for BC and low risk for adverse medication effects (B grade recommendation).
  • Clinical breast exam (CBE): USPSTF: insufficient evidence to assess clinical benefits and harms; American Cancer Society (ACS): no clear benefit Breast self-exams are no longer recommended.
  • Mammography (MMG):
    • USPSTF: Women should undergo biennial mammogram starting at aged 40 years until aged 74 years (B grade recommendation).
    • ACS: Women annual mammograms starting at aged 45 to 54 years, then women >55 years of age biennial mammograms or yearly screening if desired (1); aged 40 to 44 years, optional mammograms yearly

COMMONLY ASSOCIATED CONDITIONS

History of atypical ductal hyperplasia (ADH), atypical lobular hyperplasia (ALH), and LCIS

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