Kurian AW, et al. - In this population-based retrospective cohort study, the researchers investigated the impact of multiple-gene sequencing on the experience and treatment outcomes for patients with breast cancer. They reported that 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, but important targets for improvement include postsurgical delay and racial/ethnic disparity in variants of uncertain significance.

Methods

• From January 2013 to December 2015, patients with breast cancer diagnosed and accrued from SEER registries across Georgia and in Los Angeles, California, were surveyed (n = 5080, response rate = 70%).
• After that, responses were merged with SEER data and results of clinical genetic tests, either BRCA1 and BRCA2 (BRCA1/2) sequencing only or involving additional other genes (multiple-gene sequencing), provided by 4 laboratories.
• The main outcomes were type of testing (multiple-gene sequencing vs BRCA1/2-only sequencing), test results (negative, variant of unknown significance, or pathogenic variant), patient experiences with testing (timing of testing, who discussed results), and treatment (strength of patient consideration of, and surgeon recommendation for, prophylactic mastectomy), and prophylactic mastectomy receipt.
• According to practice guidelines, they defined a patient subgroup with higher pretest risk of carrying a pathogenic variant.

Results

• As per data, among five thousand, twenty-six patients (mean [SD] age, 59.9 [10.7]), 1316 (26.2%) were related to genetic results from any laboratory.
• Findings revealed that multiple-gene sequencing increasingly replaced BRCA1/2-only testing over time: in 2013, the rate of multiple-gene sequencing was 25.6% and BRCA1/2-only testing, 74.4%;in 2015 the rate of multiple-gene sequencing was 66.5% and BRCA1/2-only testing, 33.5%.
• It was noted that multiple-gene sequencing was more often ordered by genetic counselors (multiple-gene sequencing, 25.5% and BRCA1/2-only testing, 15.3%) and delayed until after surgery (multiple-gene sequencing, 32.5% and BRCA1/2-only testing, 19.9%).
• They observed that multiple-gene sequencing substantially increased rate of detection of any pathogenic variant (multiple-gene sequencing: higher-risk patients, 12%; average-risk patients, 4.2% and BRCA1/2-only testing: higher-risk patients, 7.8%; average-risk patients, 2.2%) and variants of uncertain significance, particularly in minorities (multiple-gene sequencing: white patients, 23.7%; black patients, 44.5%; and Asian patients, 50.9% and BRCA1/2-only testing: white patients, 2.2%; black patients, 5.6%; and Asian patients, 0%).
• The present data indicated that multiple-gene sequencing was not linked with an increase in the rate of prophylactic mastectomy use, which was highest with pathogenic variants in BRCA1/2(BRCA1/2, 79.0%; other pathogenic variant, 37.6%; variant of uncertain significance, 30.2%; negative, 35.3%).