The Importance of Testing for BRCA Mutations in OC
Multiple clinical practice guidelines recommend testing for BRCA mutations
NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Genetic/Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic
Recommend testing for high-penetrance ovarian cancer susceptibility genes (including BRCA1/2) for patients with OC, regardless of family history1
NCCN Guidelines® for Ovarian Cancer
Recommend BRCA1/2 mutation testing for patients with histologically confirmed OC2
ASCO Guidelines
Recommend BRCA mutation testing for patients with epithelial ovarian, fallopian tube, or primary peritoneal cancer3
SGO Guidelines
Recommend BRCA mutation testing for patients with high-grade epithelial ovarian, tubal, or peritoneal cancer4
BRCA mutation testing can provide important insights for you and your patients

BRCA mutations are associated with a higher risk of developing certain cancers, including BC and OC.5-7


The role of BRCA1/2 mutations in cancer risk


In healthy cells, BRCA proteins play a critical role in the repair of DNA double-strand breaks.10


Mutations in BRCA may prevent the proper repair of DNA or cause it to be repaired via more error-prone mechanisms.10


This may cause DNA damage to accumulate and eventually lead to the development of cancer.11
If a BRCA mutation is detected in someone who does not have cancer, they have the opportunity to6,12:
- Undergo more intensive screening for BRCA mutation–associated cancers
- Take preventative measures, such as prophylactic surgery

BRCA mutations may provide prognostic information about the patient’s OC.13-19

Patients with BRCA mutations may have an improved response to some treatments.18-23
Role of PARP inhibition in certain cancers with BRCA mutations


PARP plays an integral role in repairing certain types of DNA damage, including single-strand DNA breaks.24


Inhibition of PARP can disrupt this DNA repair.24


Because both BRCA and PARP are important for repairing DNA, inhibiting PARP in a cell that already has a BRCA mutation can lead to cancer cell death.11

In OC, germline or somatic BRCA mutations can determine eligibility for certain treatments.25
Because BRCA mutation status can inform treatment decisions, testing should take place when tissue is first collected.12,26
Because BRCA mutation status can inform treatment decisions, testing should take place when tissue is first collected.12,26
Watch to learn how BRCA mutations can drive the pathogenesis of OC.
ASCO, American Society of Clinical Oncology; BRCA, breast cancer susceptibility gene; NCCN, National Comprehensive Cancer Network; OC, ovarian cancer; PARP, poly ADP-ribose polymerase; SGO, Society of Gynecologic Oncology.
References: 1. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Genetic/Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic V1.2020. © National Comprehensive Cancer Network, Inc. 2019. All rights reserved. Accessed March 3, 2020. 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. 2. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Ovarian Cancer Including Fallopian Tube Cancer and Primary Peritoneal Cancer V1.2020. © National Comprehensive Cancer Network, Inc. 2020. All rights reserved. Accessed March 16, 2020. 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. 3. Lu KH et al. J Clin Oncol. 2014;32(8):833-840. 4. Lancaster JM et al; SGO Clinical Practice Committee. Gynecol Oncol. 2015;136(1):3-7. 5. Miller-Samuel S et al. Semin Oncol. 2011;38(4):469-480. 6. Larsen MJ et al. Breast Cancer (Auckl). 2014;8:145-155. 7. Committee on Practice Bulletins–Gynecology, Committee on Genetics, Society of Gynecologic Oncology. Obstet Gynecol. 2017;130(3):e110-e126. 8. National Cancer Institute. https://seer.cancer.gov/statfacts/html/ovary.html. 9. Kuchenbaecker KB et al. JAMA. 2017;317(23):2402-2416. 10. Gudmundsdottir K, Ashworth A. Oncogene. 2006;25(43):5864-5874. 11. McLornan DP et al. N Engl J Med. 2014;371(18):1725-1735. 12. Capoluongo E et al. Semin Oncol. 2017;44(3):187-197. 13. Trainer AH et al. Int J Gynecol Cancer. 2010;20(5):704-716. 14. Bolton KL et al. JAMA. 2012;307(4):382-390. 15. Chetrit A et al. J Clin Oncol. 2008;26(1):20-25. 16. Candido-dos-Reis FJ et al. Clin Cancer Res. 2015;21(3):652-657. 17. Norquist BM et al. JAMA Oncol. 2016;2(4):482-490. 18. Tan DS et al. J Clin Oncol. 2008;26(34):5530-5536. 19. Alsop K et al. J Clin Oncol. 2012;30(21):2654-2663. 20. Ledermann J et al. Lancet Oncol. 2014;15(8):852-861. 21. Kristeleit R et al. Eur J Cancer. 2015;51(suppl 3):S531. 22. Gelmon KA et al. Lancet Oncol. 2011;12(9):852-861. 23. Mirza MR et al; ENGOT-OV16/NOVA Investigators. N Engl J Med. 2016;375(22):2154-2164. 24. O’Sullivan CC et al. Front Oncol. 2014;4:42. 25. FDA.http://www.fda.gov/MedicalDevices/ProductsandMedicalProcedures/InVitroDiagnostics/ucm301431.htm. Updated March 11, 2019. Accessed April 16, 2019. 26. George A et al. Nat Rev Clin Oncol. 2017;14(5):284-296.
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