All patients with metastatic breast cancer should undergo genetic testing for inherited cancer predisposition, according to a report published by researchers from Johns Hopkins University School of Medicine and Vanderbilt Ingram Cancer Center.1

Of 100 patients with metastatic breast cancer, 14 patients were found to have pathogenic/likely pathogenic (P/LP) variants and 21 individuals were found to have a variant of unknown significance. This high prevalence of P/LP variants “could have therapeutic implications,” wrote the researchers.

To measure the prevalence of these variants, the patients underwent germline testing using a panel of 30 genes that are known to be associated with hereditary cancer. The panel, they noted, does not analyze the complete coding sequence of all tested genes. Patients were excluded from the study if they had undergone germline testing previously, unless the results of those prior tests analyzed 10 or fewer genes and no P/LP variants were found.

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Of the 14 patients with P/LP variants, 43% did not meet guidelines set by the National Comprehensive Cancer Network® (NCCN®) for genetic testing. None of the P/LP variants were of the BRCA variety, however.

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Of the 6 patients found to have BRCA variants, 2 had no prior history of genetic testing despite meeting NCCN guidelines for genetic testing. According to the researchers, these results underscore “the need for improved implementation of recommended guidelines.”

“Our results provide additional support for testing patients with metastatic breast cancer based on their relatively high prevalence of P/LP variants, including a 6% frequency of P/LP variants in BRCA,” the researchers wrote. “Furthermore, given that many of the genes included on the multigene panel are involved in DNA repair, there is scientific rationale that some of these P/LP variants (ATM, BRIP1, CHEK2) may also be predictive for response to PARP inhibitors, a hypothesis currently being tested in clinical trials (NCT03344965).”

Disclosure: Some of the authors reported financial ties with the pharmaceutical industry. For a full list of disclosures, please refer to the original paper.


Stuttgen K, Croessmann S, Fetting J, et al. Pathogenic germline variants in patients with metastatic breast cancer [published online August 29, 2019]. JAMA Oncol. doi: 10.1001/jamaoncol.2019.3116