UNDERSTANDING
THE MANY IMPLICATIONS OF gBRCA MUTATIONS

BRCA1/2 proteins are essential for DNA repair — and mutations increase the risk for cancer

  • BRCA1 and BRCA2 are human genes that produce proteins involved in DNA repair1

In normal cells2

DNA-strand-icon

In normal cells2

BRCA1/2 proteins repair breaks in DNA generated during DNA replication or damage via a repair mechanism called homologous recombination (HR)

  • When BRCA1 or BRCA2 is mutated, DNA repair may not proceed properly — which can lead to development of certain cancers, including breast cancer1

In gBRCA-mutated cancer cells2,3

broken-DNA-strand-icon

In gBRCA-mutated cancer cells2,3

HR is defective and alternative repair mechanisms
(eg, PARP enzymes) are needed to maintain DNA repair and cell proliferation

Cancer cell overreliance on alternative repair mechanisms can lead to accumulation of genetic mutations, promoting formation and survival of tumor cells

gBRCA mutations have implications for patients and families, 
​and genetic counseling can help prepare them for the journey

  • Genetic counseling by a certified genetic counselor or trained
    healthcare provider should be offered to advise patients
    appropriately both pre-testing and post-testing1,4,5
    • Pre-testing: discuss benefits of testing, review privacy
      and discrimination laws, and work with insurance
      plans on coverage or locate low-cost testing
    • Post-testing: interpret test results and
      explain what they mean for patients
      and their families
  • Coverage for genetic counseling may be provided by insurance plans for patients diagnosed with BC.6 Check with patients' insurance plan. If coverage is an issue, low-cost genetic counseling may be available.5

All patients with recurrent BC or mBC should have gBRCA testing7 — advise them on treatment options and have a genetic counselor discuss testing implications

BC=breast cancer; BRCA=breast cancer susceptibility gene; gBRCA=germline breast cancer susceptibility gene; HR=homologous recombination; mBC=metastatic breast cancer; PARP=poly (ADP-ribose) polymerase.

References: 1. National Institutes of Health, National Cancer Institute. BRCA gene mutations: cancer risk and genetic testing. National Institutes of Health website. https://www.cancer.gov/about-cancer/causes-prevention/genetics/brca-fact-sheet. Accessed February 10, 2022. 2. Lee J-m, Ledermann JA, Kohn EC. PARP inhibitors for BRCA1/2 mutation-associated and BRCA-like malignancies. Ann Oncol. 2014;25(1):32-40. 3. Lupo B, Trusolino L. Inhibition of poly(ADP-ribosyl)ation in cancer: old and new paradigms revisited. Biochim Biophys Acta. 2014;1846(1):201-215. 4. Kinney AY, Steffen LE, Brumbach BH, et al. Randomized noninferiority trial of telephone delivery of BRCA1/2 genetic counseling compared with in-person counseling: 1-year follow-up. J Clin Oncol. 2016;34(24):2914-2924. 5. Facing Our Risk of Cancer Empowered (FORCE). Support: insurance & paying for care: genetic services. https://www.facingourrisk.org/support/insurance-paying-for-care/genetic-services/overview. Accessed March 9, 2022. 6. Centers for Disease Control. Genetic counseling for hereditary breast and ovarian cancer. https://www.cdc.gov/genomics/disease/breast_ovarian_cancer/counseling.htm. Accessed April 15, 2022. 7. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Breast Cancer. V.4.2022. June 21, 2022. © National Comprehensive Cancer Network, Inc. 2022. All rights reserved. Accessed June 29, 2022. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.