Description

• Malignant neoplasm of cells native to the breast—epithelial, glandular, or stroma
• Types: ductal carcinoma in situ (DCIS), infiltrating ductal carcinoma, infiltrating lobular carcinoma, Paget disease, phyllodes tumor, inflammatory breast cancer (BC), angiosarcoma

Epidemiology

Incidence

• Estimated new female DCIS: 49,290; invasive BC: 281,550 in 2021
• Estimated deaths in 2021: females 43,600
• Incidence rates of BC have increased by 0.5% per year in recent years.

Prevalence
There are >3.8 million breast cancer survivors in US.

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 factors receptors (EGFR), leading to similar abnormal cellular replication.

Genetics

• Criteria for additional risk evaluation/gene testing in affected BC individual
  • BC at age ≤50 years
  • BC at any age and
    • ≥1 family member with BC ≤50 years of age or ovarian/fallopian tube/primary peritoneal CA
    • ≥2 family members with BC or pancreatic CA
    • Population at increased risk (e.g., Ashkenazi Jew with BC or ovarian CA at any age)
  • Triple-negative BC (ER−, PR−, HER2−)
  • Two BC primaries
  • 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 >7), leukemia, lymphoma, sarcoma, dermatologic manifestations, and/or macrocephaly, gastrointestinal (GI) hamartomas
  • Male BC
• Criteria for additional risk evaluation/gene testing in unaffected BC individual
  • First- or second-degree relative with BC ≤45 years of age
  • ≥2 breast primaries in one individual
  • ≥1 ovarian/fallopian tube/primary peritoneal CA from same side of family
  • ≥2 w/ breast primaries on same side of family
  • ≥1 family member with BC and CA of thyroid, adrenal cortex, endometrium, pancreas, CNS, diffuse gastric, aggressive prostate, leukemia, lymphoma, sarcoma, dermatologic manifestations, and/or macrocephaly, GI hamartomas
  • Ashkenazi Jew with BC/ovarian CA at any age
  • Male BC
  • Known BC susceptibility gene mutation in a family member
• BRCA1 and BRCA2 are inherited in an autosomal fashion and account for 5–10% of female and 5–20% male CAs; 15–20% familial BCs
  • Mutations higher in Ashkenazi Jewish descent
  • Mutation in BRCA raises risk to 45–65% from 7% at age 70 years.

Risk Factors

• National Cancer Institute BC Risk calculator: https://bcrisktool.cancer.gov
• Hormone replacement therapy (combination estrogen-progesterone and estrogen only agents [but not vaginal estrogen]) during perimenopause increases breast cancer risk for 10 years after medication is discontinued.
• Relative risk (RR) >4.0:
  • Age >65 years
  • Biopsy confirmed atypical hyperplasia
  • BRCA mutation
  • DCIS
  • Lobular carcinoma in situ (LCIS)
  • Personal history of early-onset BC (<40 years)
  • ≥2 first-degree relatives diagnosed at an early age
• RR 2.1 to 4.0:
  • Personal history of BC (40+ years)
  • Postmenopausal
  • History of radiation
  • First-degree relative of BC
• RR 1.1 to 2.0:
  • Alcohol use
  • Ashkenazi Jewish descent
  • Diethylstilbestrol exposure
  • Early menarche (<12 years old)
  • Late menopause (>55 years old)
  • High socioeconomic status
  • First pregnancy at >30 years
  • Proliferative breast disease without atypia (fibroadenoma or ductal hyperplasia)
  • Dense breasts (>50%)
  • Nulliparous/no history of full-term pregnancy
  • No history of breastfeeding
  • History of obesity
  • History of endometrial or ovarian CA
  • Hormone replacement therapy
  • Recent oral contraceptive pill use
  • Tall height
• Patients with 20–25% lifetime risk should receive an annual MRI beginning at age 30 years:
  • BRCA mutation
  • First-degree relative with BRCA mutation
  • History of radiation age 10 to 30 years
  • Li-Fraumeni or Cowden syndrome or first-degree relative with the same
• Patients with 15–20% lifetime risk:
  • Personal history of BC, DCIS, LCIS, atypical ductal hyperplasia, atypical lobular hyperplasia
  • History of dense or unevenly dense breasts

General Prevention

• Maintain healthy weight—obesity increases BC risk; physical activity and healthy diet are key.
• Limit alcohol use—≥1 serving of alcohol per day is recommended.
• High serum 25-OH vitamin D levels correlate with lower breast cancer risk; consider vitamin D supplementation.
• Medication: The U.S. Preventative Services Task Force (USPSTF) recommends that clinicians offer to prescribe risk-reducing medications, such as tamoxifen, raloxifene, or aromatase inhibitors, to women who are at increased risk for breast cancer and at low risk for adverse medication effects (B recommendation).
  • The National Cancer Institute Risk Assessment Tool can be used to determine risk.
  • Greater risk was defined as >3% where the risk of medication harms are low.
• Breast self-exams (BSE): American Cancer Society no longer recommend routine monthly BSE.
• Clinical breast exam (CBE):
  • USPSTF: insufficient evidence to assess clinical benefits and harms
  • American Cancer Society (ACS): no clear benefit or structured guidelines in average-risk women (1)
• Mammography:
  • USPSTF: women should undergo biennial mammogram starting at age 50 until age 74
  • American Cancer Society: Women should have annual mammograms starting at age 45 to 54, then women 55 and over should have biennial mammograms or can continue yearly screening if desired (1).
    • Women ages 40 to 44 have the choice to begin annual screening mammograms if desired.

Commonly Associated Conditions

• Genetic syndromes and mutations such as BRCA1, BRCA2, Li-Fraumeni, and Cowden disease
• History of high-risk breast lesions such as atypical ductal hyperplasia (ADH), atypical lobular hyperplasia (ALH), and LCIS
• Obesity