It’s time for comprehensive genetic testing of the germ line in breast cancer

A new study provides additional support for comprehensive germline genetic testing of affected women breast cancer.

The study found that adherence to current restrictive guidelines on germline testing is missed by a significant number of women with pathogenic or potentially pathogenic (P/LP) variants, which would alter patient management.

The study used a polygenic cancer panel from Invitae, which funded the study.

Two oncologists not involved in the analysis said that based on this and other data, the debate over universal breast cancer testing should come to an end.

Niloy Joel Samader, MD, said Medscape Medical News This study continues to support the broader use of germline genetic testing in patients with breast cancer regardless of stage of disease, family history of cancer, or age of diagnosis – factors presented in current guidelines.

“These predictors will be missing a significant number of patients who have a genetic predisposition,” said Samader, MD, of the Mayo Clinic Comprehensive Cancer Center in Phoenix, Arizona.

Julia Smith, MD, agreed that the current prospective study, along with several others, “demonstrates that it is no longer sufficient to rely entirely on the clinical judgment of health care providers, including genetic counselors, [who] It consistently misses the identification of a large number of genetic mutations that would be clinically feasible.

“The push for universal genetic testing is definitely worthwhile, and the more we do, the more we learn about what we can also do,” said Smith, of the Langone Perlmutter Cancer Center in New York City. It specializes in assessing cancer risk.

The studyIt was published online at JAMA network is openis a reanalysis of a prospective community cohort of 952 unselected patients with breast cancer who underwent comprehensive germline genetic testing using the Invitae large cancer panel.

The Preliminary studypublished in 2019, found that nearly half of the P/LP germline gene variants would have been missed had testing taken only for patients who met the 2017 National Comprehensive Cancer Network (NCCN) guidelines for genetic testing.

In the current study, Pat Whitworth, MD, of the Nashville Breast Center in Tennessee, and colleagues explored changes in clinical management that resulted from germline testing in this group. Participants were stratified based on whether or not patients met the NCCN criteria.

Whitworth and colleagues found that clinical recommendations were altered in 84% of patients (31 of 37) with P/LP variants who met the test criteria.

Clinical recommendations were also changed in 68% of patients (23 out of 34) who did not meet the testing criteria but had P/LP variants in cancer predisposition genes.

Among the off-criteria patients, clinical recommendations were changed based on genetic test results for 64% (14 of 22) of those with a variant in the breast cancer predisposition gene.

Overall, clinicians found that the test was useful for about two-thirds of patients with P/LP variants.

No changes were made to clinical recommendations for nearly all patients with negative results (345 of 349) or variants of uncertain significance (492 of 509).

There was no significant difference in the rate of P/LP variants between patients who met the BRCAPRO risk model threshold and those who did not, which helps clinicians make recommendations for genetic testing (s = .86).

Whitworth and colleagues conclude that their findings suggest that “restrictive criteria for germline genetic testing deprive patients with breast cancer of data-informed clinical management.” On the other hand, comprehensive germline testing “teaches clinical decision-making and provides access to targeted therapies and clinical trials for all breast cancer patients.”

The guidelines for genetic testing were recently expanded in colorectal cancerSamader said. The NCCN 2022 Colorectal Cancer Guidelines now invite clinicians to consider germline genetic testing for all colorectal cancer patients regardless of age at diagnosis.

“This strategy may be the way forward for many types of cancer, including breast cancer,” Samader said. “As more and more precision-targeted therapies for breast and other cancers are discovered, it is imperative that genetic sequencing, including germline and antibody testing or CT-DNA in patients with advanced cancer, becomes widely available to inform care.”

The study was funded by Invitae. Whitworth and several of the co-authors have financial relationships with Invitae. Samadder has relationships with Janssen Research and Development, Recursion Pharmaceuticals, and cancer prevention drugs. Smith has not disclosed any relevant financial relationships.

Gamma neto is open. Posted online September 22, 2022. full text

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