BRCA 1 and BRCA 2

  • BRCA 1 and BRCA 2 are genes:
    • That produce tumor suppressor proteins:
      • Which help repair damaged DNA
    • They are the most common gene alterations seen in the hereditary breast cancer population
    • They are associated with an increased risk of breast cancer estimated to be:
      • 55% to 70% for BRCA 1 carriers by age 70
      • 45% to 70% in BRCA 2 carriers by age 70
    • While both BRCA 1 and BRCA 2 mutations are associated with an increased risk of breast cancer:
      • BRCA 1 breast cancers more commonly occur in:
        • Younger
        • Premenopausal women
        • Are more likely to be triple negative
    • BRCA 1 is associated with a higher risk of ovarian cancer compared to BRCA 2:
      • With a lifetime risk of 40% to 45% in BRCA 1 carriers compared to 15% to 20% in BRCA 2 carriers
    • BRCA 2 breast cancers more closely resemble the sporadic breast cancer pattern:
      • With a predominance of hormone receptor positive cancers in women greater than 50 years
  • CHEK 2 and PALB 2 are moderate penetrance genes:
    • That are less common than BRCA mutations
    • Similar to BRCA 2 deleterious mutations:
      • CHEK 2 and PALB 2 mutations are associated with:
        • Hormone receptor positive postmenopausal breast cancer
  • Imaging surveillance for BRCA mutation carriers begins at:
    • Age 25 with annual breast MRI with contrast, with addition of mammography after age 30
    • Although use of screening ultrasound is evolving in women with dense breast tissue:
      • Its use in BRCA carriers has not been defined
  • Surveillance strategies have significantly improved early detection but do not prevent breast cancer
  • Bilateral salpingo-oophorectomy:
    • Has been shown to provide approximately 50% relative reduction in breast cancer risk:
      • But ultimately prophylactic mastectomy provides the greatest reduction
  • The optimal timing of surgery depends on multiple factors, including:
    • The patient’s desire for future breastfeeding
    • Ages of family members at diagnosis
  • Several retrospective series and meta-analyses of four prospective studies:
    • Have supported prophylactic mastectomy in BRCA mutation carriers
    • While the data demonstrate a 93% relative risk reduction in breast cancers:
      • They do not demonstrate a survival benefit in this population
  • Recent non-randomized studies have evaluated use of nipple-sparing mastectomy (NSM) and demonstrated its feasibility and safety in patients with BRCA mutation:
    • Jakub et al. reported data from 548 risk-reducing NSMs in 346 patients treated at 9 institutions
    • This study included both women opting for prophylactic mastectomies concurrent with treatment for a contralateral breast cancer, and women undergoing bilateral prophylactic mastectomies for risk reduction
    • With median and mean follow up of 34 and 56 months, respectively:      
      • No ipsilateral breast cancers occurred after prophylactic NSM
    • Breast cancer did not develop in any patients undergoing bilateral risk-reducing NSMs
  • References
    • Heemskerk-Gerritsen BA, Menke-Pluijmers MB, Jager A, et al. Substantial breast cancer risk reduction and potential survival benefit after bilateral mastectomy when compared with surveillance in healthy BRCA1 and BRCA2 mutation carriers: a prospective analysis. Ann Oncol. 2013;24(8):2029-2035.
    • De Felice F, Marchetti C, Musella A, et al. Bilateral risk-reduction mastectomy in BRCA1 and BRCA2 mutation carriers: a meta-analysis. Ann Surg Oncol. 2015;22(9):2876-2880.
    • Ludwig KK, Neuner J, Butler A. Risk reduction and survival benefit of prophylactic surgery in BRCA mutation carriers: a systematic review. Am J Surg. 2016;212(4):660-669
    • Jakub JW, Peled AW, Gray RJ. Oncologic Safety of Prophylactic Nipple-Sparing Mastectomy in a Population With BRCA Mutations: A Multi-institutional Study. JAMA Surg. 2018;153:123-129.
    • Loi M, Desideri I, Olmetto E, Francolini G, Greto D, Bonomo P, et al. BRCA mutation in breast cancer patients: Prognostic impact and implications on clinical management. Breast J. 2018;24(6):1019-1023.
    • Economopoulou P, Dimitriadis G, Psyrri A. Beyond BRCA: new hereditary breast cancer susceptibility genes. Cancer Treat Rev. 2015;41(1):1-8.

#Arrangoiz #BreastSurgeon #CancerSurgeon #SurgicalOncologist #BreastCancer #BRCA #CASO #CenterforAdvancedSurgicalOncology #Miami

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