Multiple-Gene Sequencing vs BRCA1/2-Only Testing After Breast Cancer Diagnosis


Key Points

  • Multigene sequencing has replaced BRCA1/2-only testing as the most commonly used test in clinical practice.
  • Multigene sequencing increased identification of pathogenic variants without an increase in the use of prophylactic mastectomy. 

In a retrospective cohort study reported in JAMA Oncology, Kurian et al found that use of germline multiple-gene sequencing has become more common than BRCA1/2-only sequencing after breast cancer diagnosis in clinical practice, with an associated increased detection of pathologic variants not affecting frequency of use of prophylactic mastectomy.

The study involved surveys of 5,026 patients (representing a 70% response rate in the entire population) diagnosed with breast cancer from January 2013 to December 2015 in Surveillance, Epidemiology, and End Results (SEER) registries in Georgia and Los Angeles. Responses were merged with SEER data and results of clinical genetic testing consisting of BRCA1 and BRCA2 (BRCA1/2) sequencing only or multiple-gene sequencing provided by four laboratories.

Changes in Testing and Outcomes

Among the 5,026 patients, 1,316 (26.2%) were linked to genetic results from any laboratory. Multiple-gene sequencing replaced BRCA1/2-only testing as the most-used test over time. Whereas multiple-gene sequencing accounted for 25.6% of tests and BRCA1/2-only testing 74.4% in 2013, the proportions had changed to 66.5% vs 33.5% in 2015. Multiple-gene sequencing was most often ordered by genetic counselors (25.5% vs 15.3% BRCA1/2-only testing) and was more commonly delayed until after surgery (32.5% vs 19.9% for BRCA1/2-only testing).

Multiple-gene sequencing was associated with increased detection of any pathogenic variant vs BRCA1/2-only testing among higher-risk patients (12% vs 7.8%) and average-risk patients (4.2% vs 2.2%) and increased detection of variants of uncertain significance, with detection rates of 23.7% vs 2.2% in white patients, 44.5% vs 5.6% in black patients, and 50.9% vs 0% in Asian patients. Multiple-gene sequencing was not associated with an increased use of prophylactic mastectomy, with the rate of such treatment being highest in patients with BRCA1/2 pathogenic variants, followed by other pathogenic variants (37.6%), variants of uncertain significance (30.2%), and no pathogenic variants or variants of uncertain significance (35.3%).

The investigators concluded, “Multiple-gene sequencing rapidly replaced BRCA1/2-only testing for patients with breast cancer in the community and enabled 2-fold higher detection of clinically relevant pathogenic variants without an associated increase in prophylactic mastectomy. However, important targets for improvement in the clinical utility of multiple-gene sequencing include postsurgical delay and racial/ethnic disparity in variants of uncertain significance.”

The study was supported by the National Cancer Institute; a University of Michigan Cancer Center Biostatistics, Analytics, and Bioinformatics shared resource grant; and others.

Allison W. Kurian, MD, of Stanford University School of Medicine, is the corresponding author for the JAMA Oncology article.

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®.