Why do I need to perform BRCA testing early

Why do I need to perform BRCA testing early?

The identification of BRCA1/2 and other mutations, the increasing availability of genomic testing, and the development of therapies that target some of these mutations have significantly changed the evaluation and management of ovarian cancer.

Ovarian cancer is the fifth most common type of cancer in women, with low survival rates, largely driven by late stage diagnoses.^1,2 Improving prevention and early detection is a priority because disease diagnosed at a local stage has a 5-year relative survival rate of 93%.²

The majority of ovarian cancers are high-grade serous epithelial carcinomas, which carry the worst prognosis, as they are clinically aggressive neoplasms that are usually diagnosed at an advanced stage.³ Ovarian cancers that present BRCA1 and BRCA2 mutations show almost exclusive association with epithelial ovarian carcinoma.⁴

Historically, BRCA testing was used mainly as a means to assess an individual’s risk of recurrence, their risk of developing other BRCA-related cancers, the likelihood of the mutation being passed onto relatives, and their own hereditary risk. Now, germline BRCA tests can be used to inform treatment decisions, by tailoring treatments based on the presence or absence of different biomarkers.^5,6

Historical and Current use of BRCA Testing

Testing is important to understand a patient’s options:^7,8

Prognostic implications:^9-11

Patients with a BRCA mutation are more likely to develop visceral metastases than BRCA wild-type patients⁹
Patients with a BRCA mutation may also benefit from longer have increased survival than those without a BRCA mutation^10,11

Monitoring needs:^12,13

Patients with a BRCA mutation have an increased risk of developing certain cancers such as ovarian cancer, breast cancer, pancreatic cancer and prostate cancer¹²
Identifying patients with a BRCA mutation can influence patient management and point towards risk reduction methods where necessary¹³

Familial implications:^7,14

Patients with a germline BRCA mutation can pass this on to their offspring or may have siblings who carry a germline BRCA mutation. Such family members may therefore benefit from an accurate cancer risk assessment and individualised screening/prevention^7,14

Test routinely to inform treatment decisions

Testing is important to help inform treatment decisions for patients with ovarian cancer. Guidelines recommend germline and somatic BRCA testing to help inform treatment options.^13,15

BRCA1/2 mutations can be present with older age and an absent family history⁸

Test routinely to evaluate hereditary risk

The presence of a germline BRCA mutation increases the risk of development of ovarian cancer as well as several other common cancers, including breast, prostate and pancreatic.¹²

There is a 50% chance of a child inheriting a BRCA mutation from a mother or father carrying a harmful mutation. Therefore, the results of germline BRCA testing of a diagnosed patient with ovarian cancer can help to identify any family members who could be at risk of developing the disease.¹²

All patients with ovarian cancer are eligible for testing for high-penetrance ovarian cancer susceptibility genes, such as BRCA1/2.¹³ For patients without a diagnosis of ovarian cancer, eligibility for testing is based on the presence of factors understood to be associated with an increased likelihood of harbouring a germline BRCA mutation.^12,13

References and abbreviations

BICR, blinded independent central review; BRCA, breast cancer gene; ESMO, European Society for Medical Oncology; gBRCA, germline BRCA; INV, investigator-assessed; OC, ovarian cancer; PARP, poly-adenosine diphosphatase ribose polymerase; PARPi, PARP inhibitor; PFS, progression-free survival; PSR=platinum-sensitive relapsed.

References:

Ledermann JA et al. Ann. Oncol. 2013. 24 (Supplement 6): vi24–vi32.
Torre LA et al. Ca Cancer Clin. 2018; 68: 284-296.
Koshiyama M et al. Diagnostics. 2017; 7: 12. doi: 10.3390/diagnostics7010012.
Schrader A et al. Obstetrics & Gynecology. 2012; 120(2): 235-240.
Hoogerbrugge N and Jongmans MC. Eur J Hum Genet. 2016; 24: S19-S26.
Pal T et al. Cancer Control. 2012; 19: 255-66.
Larsen MJ et al. Breast Cancer (Auckl). 2014: 8; 145-155.
Aslop K et al. J. Clin. Oncol. 2012; 30(21): 2654-2663.
Gourley C et al. J Clin Oncol. 2010; 28: 2505–2511.
Tan D & Kaye S. Am Soc Clin Oncol Educ Book. 2015: doi: 10.14694/EdBook_AM.2015.35.114.
Bolton K et al. JAMA. 2012; 307: 382–390.
National Cancer Institute. BRCA Gene Mutations: Cancer Risk and Genetic Testing. Available at: https://www.cancer.gov/about-cancer/causes-prevention/genetics/brca-fact-sheet [Accessed March 2021].
Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines^®) for Genetic/Familial High-Risk Assessment: Breast, Ovarian and Pancreatic V2.2021. National Comprehensive Cancer Network, Inc. All rights reserved. [Accessed March 2021]. To view the most recent and complete version of the guideline go online to NCCN.org.
National Cancer Institute. NCI Dictionary of Terms – germline mutation. Available at: https://www.cancer.gov/publications/dictionaries/cancer-terms/def/germline-mutation [Accessed March 2021].
Colombo N et al. Ann Oncol. 2019; 30(5): 672-705.
Ledermann JA et al. Ann. Oncol. 2016; 27 (S1): 40–44.
Moore K et al. N Eng J Med. 2018; 379(26): 2495-2505.
Taylor and Scott 2020. PARP inhibitors: Choosing what to use in epithelial ovarian cancer. Available at: https://www.contemporaryobgyn.net/view/parp-inhibitors-choosing-what-to-use-in-epithelial-ovarian-cancer. [Accessed March 2021].
Penson R, et al. J Clin Oncol. 2020; 38: 1164-1174.
González-Martin A et al. N Eng J Med. 2019; 381(25): 2391-2402.
Moore K et al. N Eng J Med. 2018; 379(26): 2495-2505:Supplementary Appendix.
Banerjee S et al. Presented at ESMO Virtual Congress 2020. 19–21 September. Abstract #811MO.
Coleman R et al. The Lancet. 2017; 390(10106): 1949-1961.
FDA Multi-disciplinary Review: Niraparib. APPLICATION NUMBER: 208447Orig1s000. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208447Orig1s000MultidisciplineR.pdf. [Accessed March 2021].
Pujade-Lauraine E et al. Lancet Oncol. 2017; 18: 1274-1284.