Abstract ES6-1: Who should have germline testing for hereditary breast cancer?
Authors: Tung N 
Published: March 2020

Who should have germline testing for hereditary breast cancer?

Several guidelines exist for who should be offered germline testing for mutations in breast and ovarian cancer susceptibility genes. NCCN guidelines currently recommend germline BRCA testing for all patients with epithelial ovarian /fallopian tube/primary peritoneal cancer, pancreatic cancer, metastatic/advanced prostate cancer. Testing is also recommended for anyone for whom a BRCA mutation has been identified in the family or for whom a tumor somatic BRCA mutation has been identified (in any tumor type). Among breast cancer patients, NCCN testing criteria include: young age at diagnosis, triple negative disease, Ashkenazi Jewish heritage, male gender, and a personal or family history of ovarian, pancreatic cancer, aggressive prostate cancer or other breast cancer. This year, USPSTF updated their genetic testing guidelines for BRCA1/2. These updates will be reviewed. It is important not to forget testing for germline mutations in other high-penetrance breast cancer susceptibility genes and to retest individuals who previously had BRCA genetic testing and may be appropriate candidates for multi-gene testing.

Recently, the American Society of Breast Surgeons has endorsed germline testing for mutations in BRCA1/2 and PALB2 for all breast cancer patients. Data that led to this recommendation will be reviewed as well as arguments for and against this recommendation. It is noteworthy that only 0.6% of breast cancer patients who did not meet current NCCN guidelines for genetic testing were found to have a germline mutation in BRCA1 or BRCA2 and 0.8% in any high-penetrance breast cancer susceptibility gene.

It is important for oncologists to be able to recognize which findings on a tumor genomic profile should prompt a recommendation for germline testing. This includes the ability to recognize cancer susceptibility genes amongst the list of actionable findings endorsed by the ACMG, as well as cancer susceptibility genes for which there are published management recommendations.

Recently, it has been recommended that germline BRCA testing be offered to all Ashkenazi Jewish individuals regardless of personal or family history of cancer since one in forty Ashkenazi individuals have a mutation in one of three BRCA founder mutations. BRCA mutations are 10 times more common in people with Ashkenazi Jewish ancestry, and up to half of BRCA mutations in this population occur in individuals without a known family history. Three-site Ashkenazi BRCA testing allows streamlined inexpensive BRCA testing without variants of unknown significance (VUS). One concern relates to how large population testing can be carried out, highlighting the need for new genetic testing service models.

Finally, arguments for and against population genetic testing for non-Ashkenazi individuals will be discussed. As the likelihood of identifying a mutation and the penetrance of the mutations identified decreases, and the frequency of VUS increases, the potential for causing harm through unnecessary screening and prevention strategies can outweigh the benefit of providing cancer risk information through testing.

Citation Format: N Tung. Who should have germline testing for hereditary breast cancer? [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr ES6-1.