Why do I need to perform BRCA testing early

Importance of early testing

Genetic testing is used predominantly to determine the BRCA pathogenic mutation status and assess the cancer risk in patients with a high probability of an inherited predisposition, which is currently based in particular on a family history of breast and ovarian cancer.¹

In Egypt, breast cancer is the most common malignancy in women, accounting for 38.8% of cancers in this population, with the estimated number of breast cancer cases nearly 22,700 in 2020 and forecasted to be approximately 46,000 in 2050.²

Deleterious germline mutations in BRCA1 and BRCA2 increase the risk of breast and ovarian cancer in women.³

It is well established that individuals carrying a germline BRCA1 or BRCA2 pathogenic mutation have an elevated lifetime risk of developing ovarian cancer or breast cancer, those who are confirmed as carrying a germline BRCA pathogenic mutation can then take appropriate action in order to prevent cancer or have cancer diagnosed as early as possible for better treatment options.¹

Germline testing is important to understand a patient’s:

Predisposition:

BRCA1 and BRCA2 are highly penetrant tumor-suppressor genes, and a deleterious germline mutation confers a high risk for breast and ovarian cancers and an increased risk for certain other malignancies, including pancreatic and prostate.⁴

Treatment options:

More than 50% of pathogenic germline variants are mutations in the BRCA1 and BRCA2 genes, using genetic testing to identify patients who are at increased risk to develop breast cancer enables patients to take steps to reduce this risk.⁵

Monitoring needs:

Identification of patients with pathogenic variants in these genes can influence patient management in terms of high-risk screening and risk reduction as well as therapeutic options related to surgery. ⁵

Early and rapid BRCA testing has already been introduced in the workflow of many centers for newly diagnosed women with breast cancer who have characteristics of an inherited predisposition, in order to inform surgical decisions and to guide management decisions.¹

Test routinely to inform treatment decisions

ABC 4/ESMO guidelines state genetic testing should be considered as early as possible in ABC in the advanced breast cancer (ABC) setting.⁶

In the ABC setting, results from genetic testing may have therapeutic implications and should therefore be considered as early as possible.

Genes to be tested for depend on personal and family history; however, at present, only germline mutations in BRCA1/2 have proven clinical utility and therapeutic impact.

Testing for other additional moderate to high penetrance genes may be considered if deemed appropriate by the geneticist.

For patients with newly diagnosed breast cancer, identification of a mutation may impact local treatment recommendations (surgery and potentially radiation) and systemic therapy.⁵

Test routinely to evaluate hereditary risk

The presence of a germline BRCA mutation increases the risk of the development of breast cancer as well as several other common cancers, including ovarian, prostate, and Pancreatic.⁷
There is a 50% chance of a child inheriting a BRCA mutation from a mother or father carrying a harmful mutation. Identifying a germline BRCA mutation in a patient diagnosed with breast cancer can help to identify any family members who would benefit from germline mutation testing, as they may be at a higher risk of developing the disease.⁷
Eligibility for testing is based on the presence of factors understood to be associated with an increased likelihood of harboring a germline BRCA mutation but priority is still largely given to patients with a hereditary risk.⁷

References and abbreviations

ABC, advanced breast cancer; BRCA, breast cancer gene; ESMO, European Society for Medical Oncology; gBRCA, germline BRCA.

References:

Hoogerbrugge N and Jongmans MC. Finding all BRCA pathogenic mutation carriers: best practice models. European Journal of Human Genetics (2016) 24, S19-S26.
Cancer Control in Egypt - The ASCO Post available at: https://ascopost.com/issues/march-25-2021/cancer-control-in-egypt/ Accessed May 2022.
D Leongamornlert et al. Germline BRCA1 mutations increase prostate cancer risk. British Journal of Cancer (2012) 106, 1697–1701.
Miller-Samuel S, MacDonald DJ, Weitzel JN, et al. Variants of Uncertain Significance in Breast Cancer-Related Genes: Real-World Implications for a Clinical Conundrum. Part One: Clinical Genetics Recommendations. Semin Oncol. 2011; 38: 469-480.
Manahan ER et al. Consensus Guidelines on Genetic Testing for Hereditary Breast Cancer from the American Society of Breast Surgeons. Ann Surg Oncol. 2019; 26: 3025-3031.
Cardoso F et al. 4th ESO–ESMO International Consensus Guidelines for Advanced Breast Cancer. Ann Oncol. 2018: 29; 1634-1657.
National Cancer Institute. BRCA1 and BRCA2: Cancer Risk and Genetic Testing. Available at: https://www.cancer.gov/about-cancer/causes-prevention/genetics/brca-fact-sheet [Accessed March 2022].