Breast Cancer
Basics
Most commonly diagnosed cancer (CA) in women and the second most common cause of CA death for U.S. women; females have a ~2.5% or 1 in 39 chance of dying from breast cancer (BC) in the United States.
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 BC, angiosarcoma
- 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 2023: ~297,790 new cases of invasive BC, ~55,720 DCIS; ~43,700 deaths from BC in U.S women; increased by ~0.5% per year since mid-2000s
Prevalence
>3.8 million BC survivors in the United States (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 (EGFRs), 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 in men) or ovarian/fallopian tube/primary peritoneal CA at 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 (CNS), diffuse gastric, aggressive prostate (Gleason score of >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- 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 with 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 Jewish descent with BC/ovarian CA at any age
- 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 account for
- 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 Tool. https://bcrisktool.cancer.gov
- Female sex; increased age
- 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.
- Age >65 years, biopsy confirmed atypical hyperplasia, DCIS, lobular carcinoma in situ (LCIS)
- BRCA mutation, Ashkenazi Jewish descent
- Personal or family history of BC at a younger age
- Postmenopausal
- History of radiation or diethylstilbestrol (DES) exposure (especially at a young age)
- Increased alcohol use
- Proliferative breast disease without atypia (fibroadenoma or ductal hyperplasia)
- Dense breasts (>50%)
- Reproductive factors
- Nulliparous, no history of full-term pregnancy or breastfeeding
- Early menarche (<12 years old), late menopause (>55 years old), first pregnancy at >35 years old
- Obesity
- Tall stature
- History of endometrial or ovarian CA
General Prevention
- Maintain healthy weight/body mass index (BMI)—obesity increases BC risk.
- Limit alcohol use—≤1 serving of alcohol per day is recommended.
- High serum 25-OH vitamin D levels correlate with lower BC risk; consider vitamin D supplementation.
- Medication: U.S. Preventive Services Task Force (USPSTF) recommends that clinicians offer to prescribe risk-reducing medications, such as tamoxifen, raloxifene, or aromatase inhibitors (AIs), to women who have a >3% risk for BC and low risk for adverse medication effects (B grade recommendation).
- Breast self-exams (BSEs): no longer recommended
- Clinical breast exam (CBE): USPSTF: insufficient evidence to assess clinical benefits and harms; American Cancer Society (ACS): no clear benefit
- Mammography (MMG):
- USPSTF: Women should undergo biennial mammogram starting at age 40 years until age 74 years (B grade recommendation).
- ACS: Women annual mammograms starting at age 45 to 54 years and then women >55 years old biennial mammograms or yearly screening if desired (1); age 40 to 44 years, optional mammograms yearly
Commonly Associated Conditions
- Li-Fraumeni and Cowden disease
- History of atypical ductal hyperplasia (ADH), atypical lobular hyperplasia (ALH), and LCIS
- Obesity
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Citation
Domino, Frank J., et al., editors. "Breast Cancer." 5-Minute Clinical Consult, 33rd ed., Wolters Kluwer, 2025. Medicine Central, im.unboundmedicine.com/medicine/view/5-Minute-Clinical-Consult/116089/all/Breast_Cancer.
Breast Cancer. In: Domino FJF, Baldor RAR, Golding JJ, et al, eds. 5-Minute Clinical Consult. Wolters Kluwer; 2025. https://im.unboundmedicine.com/medicine/view/5-Minute-Clinical-Consult/116089/all/Breast_Cancer. Accessed October 7, 2024.
Breast Cancer. (2025). In Domino, F. J., Baldor, R. A., Golding, J., & Stephens, M. B. (Eds.), 5-Minute Clinical Consult (33rd ed.). Wolters Kluwer. https://im.unboundmedicine.com/medicine/view/5-Minute-Clinical-Consult/116089/all/Breast_Cancer
Breast Cancer [Internet]. In: Domino FJF, Baldor RAR, Golding JJ, Stephens MBM, editors. 5-Minute Clinical Consult. Wolters Kluwer; 2025. [cited 2024 October 07]. Available from: https://im.unboundmedicine.com/medicine/view/5-Minute-Clinical-Consult/116089/all/Breast_Cancer.
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