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Multigene Panel Testing for Hereditary Breast and Ovarian Cancer Risk Assessment

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Key Points

  • Among the 1,046 women participating in the study, 3.8% of them (40 women) who tested negative for BRCA1 and BRCA2 had harmful mutations in other moderate-risk genes.
  • Among 63 women who tested positive for mutations, the majority of them (33 women [52%]) would be considered for additional disease-specific screening and/or prevention measures beyond those based on personal and family histories alone.
  • In the large majority of mutation-positive cases (58 of 63 [92%]), personal and/or family histories included cancer associated with the mutant genes.

Multigene testing of women who tested negative for BRCA1 and BRCA2 found some of them harbored other harmful genetic mutations—most commonly, moderate-risk breast and ovarian cancer genes, as well as Lynch syndrome genes (which increase the risk of ovarian cancer)—according to an article by Desmond et al in JAMA Oncology.

Multigene panel genetic tests are increasingly recommended for patients evaluated for a predisposition to hereditary breast/ovarian cancer. However, the rapid introduction of these tests has raised concerns, because many of the tested genes are low- to moderate-risk genes for which consensus management guidelines have not been introduced or were introduced only very recently, according to the study background.

Leif W. Ellisen, MD, PhD, of Massachusetts General Hospital Cancer Center, and coauthors wanted to determine how often multigene panel testing would identify mutations that warranted some clinical action among women appropriately tested but lacking BRCA1 and BRCA2 mutations.

Study Findings

The authors enrolled 1,046 women and performed multigene panel testing on all of them. Among these women, 3.8% of them (40 women) who tested negative for BRCA1 and BRCA2 had harmful mutations in other moderate-risk genes.

The authors included an additional 23 patients in the study’s clinical management analysis. Results indicated that among 63 women who tested positive for mutations, the majority of them (33 women [52%]) would be considered for additional disease-specific screening and/or prevention measures beyond those based on personal and family histories alone. Additional family testing also would be considered for first-degree relatives, according to the results. In the large majority of mutation-positive cases (58 of 63 [92%]), personal and/or family histories included cancer associated with the mutant genes.

“Multigene panel testing for patients with suspected hereditary breast/ovarian cancer risk identifies substantially more individuals with relevant cancer risk gene mutations than does BRCA1/2 testing alone. Identifying such mutations is likely to change management for the majority of these individuals and their families in the near term, and in the long term, should lead to development of effective management guidelines and improved outcomes for at-risk individuals,” the study concluded.

Dr. Ellisen is the corresponding author of the JAMA Oncology article.

This study was funded by Massachusetts General Hospital Friends Fighting Breast Cancer, the Tracey Davis Memorial Fund, and the Breast Cancer Research Foundation. 

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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