Nearly half of patients with breast cancer who, on multigene panel testing, are found to have a pathogenic or likely pathogenic variant for breast cancer do not meet current National Comprehensive Cancer Network (NCCN) guidelines for genetic testing, new research shows.

In a cohort of 959 women who were either currently undergoing treatment or had previously been treated for breast cancer, 49.9% met established 2017 NCCN germline genetic testing guidelines, and 50% did not, lead author Peter Beitsch, MD, Dallas Surgical Group TME/Breast Care Network, Texas, and colleagues report. Of those patients who met NCCN guidelines for germline testing, 9.39% had either a pathogenic or a likely pathogenic variant; 7.9% of those who did not meet the guidelines also had a pathogenic or likely pathogenic variant. The difference between the two groups was not statistically significant, the investigators add.

"Researcher results indicate that nearly half of patients with breast cancer with a P/LP [pathogenic/likely pathogenic] variant with clinically actionable and/or management guidelines in development are missed by current testing guidelines," the investigators observe."We recommend that all patients with a diagnosis of breast cancer undergo expanded panel testing," they conclude. The study was published online December 7 in the Journal of Clinical Oncology. However, in a related editorial, breast cancer experts argue that widespread testing would detect genetic variants of unknown significance for which there are currently no established clinical courses of action.

Cancer Genetic Testing

For their study, Beitsch and colleagues set up a multicenter, prospective registry with the help of 20 community and academic sites, all of which were experienced in cancer genetic testing and counseling. They focussed on 959 patients who had a history of breast cancer but had not undergone prior single-gene or multigene testing.  "All patients underwent germ line genetic testing with a multicancer panel of 80 genes," the authors explain. "Overall, 83 (8.65%) of 959 patients had a P/LP variant," they write. The investigators then considered findings from only BRCA1 and BRCA2 genetic testing.

In this subgroup analysis, positive BCRA1/2 rates were fourfold higher among those who met current NCCN germline testing guidelines, at 2.51%, compared to those who did not, at 0.63% (P = .020). In contrast, rates of variants of "uncertain significance" were virtually identical between those who met current NCCN guidelines for genetic testing and those who did not. "Carriers of clinically actionable variants in genes other than BRCA1/2 are likely to fall outside of the current guidelines," Beitsch and colleagues point out.