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BRCA1/BRCA2 genotyping

Indications: - newly diagnosed breast cancer [1] - age < 45 years - family history of breast cancer or ovarian cancer - triple negative (ER-, PR-, HER2-) < 60 years [1] - 2 1st-degree relatives with breast cancer, one at <= 50 years of age [1]* - >= 3 1st- or 2nd-degree relatives with breast cancer - both breast cancer & ovarian cancer among 1st- or 2nd-degree relatives - a 1st-degree relative with bilateral breast cancer - >= 2 1st- or 2nd-degree relatives with ovarian cancer - a 1st- or second-degree relative with both breast cancer & ovarian cancer - a male relative with breast cancer - if of Ashkenazi Jewish heritage, any 1st degree relative or 2 2nd degree relatives on the same side of the family with breast cancer or ovarian cancer [1]* - women who have relatives with BRCA-related cancers* - men with high-risk prostate cancer [1] * USPSTF recommendations Clinical significance: - BRCA-related cancers include: - breast cancer - ovarian cancer - peritoneal cancer - fallopian tube cancer - prostate cancer [1] - cumulative risk for breast cancer by age 80 - 72% in BRCA1 carriers & 69% in BRCA2 carriers - cumulative risk for ovarian cancer by age 80 - 44% in BRCA1 carriers & 17% in BRCA2 carriers [5] Genetics: - inheritance is autosomal dominant with incomplete penetrance Laboratory: - serum CA-125 every 6 months beginning at age 30 years [1] Radiology: - women with BRCA gene mutation should begin breast cancer screening at age 25 with MRI & mammography beginning at age 30 years - semi-annual tranvaginal ultrasound beginning at age 30 years [1] Management: - prophylactic bilateral mastectomy reduces risk of breast cancer 90% in women with BRCA gene mutation - prophylactic bilateral salpingo-oophrectomy at age 35-40 years reduces risk of ovarian cancer 80% in women with BRCA gene mutation Notes: - most women undergoing BRCA genotyping do not receive counseling from a genetic counselor [3]

Related

BRCA1/BRCA2 gene mutation positive breast cancer type 1 susceptibility protein (BRCA1) breast cancer type 2 susceptibility protein (Fanconi anemia group D1 protein, BRCA2, FACD, FANCD1)

General

breast/ovarian cancer genotyping

References

  1. Medical Knowledge Self Assessment Program (MKSAP) 16, 17, 19. American College of Physicians, Philadelphia 2012, 2015, 2021
  2. Moyer VA et al Risk Assessment, Genetic Counseling, and Genetic Testing for BRCA-Related Cancer in Women: U.S. Preventive Services Task Force Recommendation Statement. Ann Intern Med. Published online 24 December 2013 PMID: 24366376 http://annals.org/article.aspx?articleid=1791499
  3. Armstrong J et al. Utilization and outcomes of BRCA genetic testing and counseling in a national commercially insured population: The ABOUT study. JAMA Oncol 2015 Oct 1 PMID: 26426480 - Narod S. Genetic testing for BRCA mutations today and tomorrow - about the ABOUT study. JAMA Oncol 2015 Oct 1; PMID: 26426337
  4. Malone KE, Begg CB, Haile RW et al Population-based study of the risk of second primary contralateral breast cancer associated with carrying a mutation in BRCA1 or BRCA2. J Clin Oncol. 2010 May 10;28(14):2404-10 PMID: 20368571
  5. Kuchenbaecker KB, Hopper JL, Barnes DR et al. Risks of breast, ovarian, and contralateral breast cancer for BRCA1 and BRCA2 mutation carriers. JAMA 2017 Jun 20; 317:2402. PMID: 28632866 http://jamanetwork.com/journals/jama/article-abstract/2632503
  6. U.S. Preventive Services Task Force (USPSTF) Draft Recommendation Statement BRCA-Related Cancer: Risk Assessment, Genetic Counseling, and Genetic Testing. https://www.uspreventiveservicestaskforce.org/Page/Document/draft-recommendation-statement/brca-related-cancer-risk-assessment-genetic-counseling-and-genetic-testing1 - U.S. Preventive Services Task Force (USPSTF) Draft Evidence Review Draft Evidence Review for BRCA-Related Cancer: Risk Assessment, Genetic Counseling, and Genetic Testing https://www.uspreventiveservicestaskforce.org/Page/Document/draft-evidence-review/brca-related-cancer-risk-assessment-genetic-counseling-and-genetic-testing1
  7. Breast Cancer Genetics Referral Screening Tool https://www.breastcancergenescreen.org/startScreen.aspx?path=p - Ontario Family History Assessment Tool https://www.timeofcare.com/ontario-family-history-assessment-tool/ - Breast Cancer Genetics. Referral Screening Tool https://www.breastcancergenescreen.org/startScreen.aspx