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Breast Cancer

Breast Cancer is a topic covered in the 5-Minute Clinical Consult.

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  • Malignant neoplasm of cells native to the breast—epithelial, glandular, or stroma
  • Types: DCIS, infiltrating ductal carcinoma, infiltrating lobular carcinoma, Paget disease, phyllodes tumor, inflammatory breast cancer, angiosarcoma
  • Molecular subtypes: luminal A (HR+/HER2−), triple negative (HR−/HER2−), luminal B (HR+/HER2+), HER2-enriched (HR−/HER2+)


  • Estimated new female breast cancer (BC) cases for in situ 63,410; invasive 252,710 in 2017
  • Estimated new male BC cases 2,470
  • Estimated deaths 2017 females 40,610; males 440
  • Most commonly diagnosed cancer and the second most common cause of cancer death for U.S. women

Estimated >3.1 million of 164 million U.S. women (1.9%) as of March 1, 2017 (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 (2).
  • 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.

  • Criteria for additional risk evaluation/gene testing in affected individual (2)[A]
    • 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 any age or ≥2 family members with BC or pancreatic CA any age or 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 in single patient
    • Ovarian/fallopian tube/primary peritoneal CA
    • 1+ family member with BC and CA of thyroid, adrenal cortex, endometrium, pancreas, CNS, diffuse gastric, aggressive prostate (Gleason >7), leukemia, lymphoma, sarcoma, dermatologic manifestations, and/or macrocephaly, GI hamartomas
    • Male BC
    • Known BC susceptibility gene mutation in family
  • 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 or ≥1 ovarian/fallopian tube/primary peritoneal CA from same side of family or ≥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 (Gleason >7), leukemia, lymphoma, sarcoma, dermatologic manifestations, and/or macrocephaly, GI hamartomas
    • Ashkenazi Jewish with breast/ovary cancer at any age
    • Male BC
    • Known BC susceptibility gene mutation in family
  • BRCA1 and BRCA2 are inherited in an autosomal fashion and account for 5–10% of female and 5–20% male cancers; 15–20% familial BCs
    • Mutations higher in Ashkenazi Jewish descent (2%)
    • Mutation in BRCA raises risk to 45–65% from 7% at age 70 years.
  • Other genes: ATM, BARD1, BRIP, CDH1, PTEN, STK11, CHEK2, p53, ERBB2, DIRAS3, NBN, RAD50, RAD51
  • Cowden syndrome (PTEN): autosomal dominant, BC, hamartomas of skin, intestine, oral mucosa (trichilemmoma), microencephaly, endometrial CA, nonmedullary thyroid CA, benign thyroid lesions
  • Li-Fraumeni syndrome (TP53): autosomal dominant, BC and CA in CNS, leukemia, sarcoma, osteosarcoma, adrenal cortex
  • Ataxia-telangiectasia (ATM): autosomal recessive, ataxia, telangiectasia, lymphoma, leukemia, CA of breast, stomach, ovary
  • Peutz-Jeghers (STK11): autosomal dominance; hamartomatous polyps of GI tract, mucocutaneous melanin in lips, buccal mucosa, fingers, toes; CA in GI, lung, breast, uterus, ovary

Risk Factors

  • Risk assessment tool: http://www.cancer.gov/bcrisktool/
  • Relative risk increase:
  • >4.0: age >65 years, atypical hyperplasia, BRCA mutation, DCIS, LCIS, personal history <40 years, two or more first-degree relatives at early age
  • 2.1 to 4.0 RR: postmenopausal, radiation history, dense breasts (>50%), single first-degree relative
  • 1.1 to 2.0 RR: EtOH, Ashkenazi Jewish, DES exposure, early menarche, high socioeconomic status, first pregnancy >30 years, fibroadenoma, never breastfed, no full-term pregnancies, obesity, personal history >40 years, personal history of endometrial, ovarian, colon cancer, HRT long term, recent OCP use
  • 20–25% lifetime risk: 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
  • 15–20% lifetime risk: personal history of BC, DCIS, LCIS, atypical ductal hyperplasia, atypical lobular hyperplasia, dense or unevenly dense breasts

General Prevention

  • Maintain healthy weight—obesity increases BC risk; limit high carbohydrates.
  • Be physically active—150 minutes of moderate-intensity or 75 minutes vigorous activity weekly.
  • Eat healthy diet—limit processed/red meat, 7 to 10 servings of vegetables and fruits daily; limit refined-grain.
  • Limit EtOH—moderate alcohol use increases risk of BC.
  • Clinical breast exam (CBE):
    • USPFTF: insufficient evidence to assess clinical benefits and harms (3)[A]
    • ACS: does not recommend in average risk
  • Mammography:
    • USPSTF: women biennial at age 50 to 74 years (3)[B]
    • ACS: women yearly mammograms at age 45 years and can change to every other year beginning at age 55 years

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Stephens, Mark B., et al., editors. "Breast Cancer." 5-Minute Clinical Consult, 27th ed., Wolters Kluwer, 2019. Medicine Central, im.unboundmedicine.com/medicine/view/5-Minute-Clinical-Consult/116089/all/Breast_Cancer.
Breast Cancer. In: Stephens MB, Golding J, Baldor RA, et al, eds. 5-Minute Clinical Consult. 27th ed. Wolters Kluwer; 2019. https://im.unboundmedicine.com/medicine/view/5-Minute-Clinical-Consult/116089/all/Breast_Cancer. Accessed April 21, 2019.
Breast Cancer. (2019). In Stephens, M. B., Golding, J., Baldor, R. A., & Domino, F. J. (Eds.), 5-Minute Clinical Consult. Available from https://im.unboundmedicine.com/medicine/view/5-Minute-Clinical-Consult/116089/all/Breast_Cancer
Breast Cancer [Internet]. In: Stephens MB, Golding J, Baldor RA, Domino FJ, editors. 5-Minute Clinical Consult. Wolters Kluwer; 2019. [cited 2019 April 21]. Available from: https://im.unboundmedicine.com/medicine/view/5-Minute-Clinical-Consult/116089/all/Breast_Cancer.
* Article titles in AMA citation format should be in sentence-case
TY - ELEC T1 - Breast Cancer ID - 116089 ED - Stephens,Mark B, ED - Golding,Jeremy, ED - Baldor,Robert A, ED - Domino,Frank J, BT - 5-Minute Clinical Consult, Updating UR - https://im.unboundmedicine.com/medicine/view/5-Minute-Clinical-Consult/116089/all/Breast_Cancer PB - Wolters Kluwer ET - 27 DB - Medicine Central DP - Unbound Medicine ER -