Abstract P4-06-07: Trends and results of BRCA1/2 and multigene panel testing in newly diagnosed breast cancer patients
Authors: Kurian AW , Katz SJ 
Published: February 2018

Background: Next-generation sequencing technology, reduced costs and public interest have fueled a surge in more expansive germline genetic testing of breast cancer patients. However, there are no population-based data on trends in use of different test types or the distribution of results.

Methods: In the iCanCare study, we surveyed 7,303 women diagnosed in 2013-15 with early-stage breast cancer and reported to the Georgia and Los Angeles County SEER registries. Of 5,080 respondents (response rate 70%), 5,050 were linked to SEER clinical data and to test results from four commercial laboratories that performed nearly all germline genetic testing for breast cancer patients in the regions. We examined trends in test type (two genes, BRCA1/2 only, vs. more cancer susceptibility genes, multigene panel) and patterns of results (positive for a pathogenic mutation; variant of uncertain significance (VUS); negative) by clinical and sociodemographic subgroups. Pre-test risk of having a pathogenic mutation was categorized as higher vs. average based on patient report of age at diagnosis, family cancer history, ancestry (Ashkenazi Jewish vs. not) and breast cancer subtype (triple-negative vs. not), according to practice guidelines criteria for genetic testing.

Results: The mean age was 62 years; 26%, 49% and 25% had stage 0, I, and II cancer, respectively; 78% had estrogen receptor-positive, HER2-negative disease, and 9% had triple-negative; 28% had higher pre-test risk of having a pathogenic mutation; 56% were non-Hispanic white, 18% African American, 14% Hispanic, and 10% Asian. Genetic testing use did not change over time (p=0.695), with one-quarter of patients receiving any test (either BRCA1/2 only or multigene panel) according to clinical laboratory data. However, testing included more genes over time: multigene panels comprised 19% of tests in 2013 vs. 66% in 2015 (p&lt;0.001). Among all patients, 14% received BRCA1/2 only and 12% multigene panel testing, with no differences in test type by pre-test risk or race/ethnicity. Among all patients, 7% had a pathogenic mutation and 14% had a VUS in any gene. Patients at high pre-test risk had a lower ratio of uninformative VUS to informative pathogenic mutations (14%/10%) than average risk patients (15%/4%, p&lt;0.001). There was a substantially higher ratio of VUS to pathogenic mutation among African Americans (22%/7%) and Asians (23%/3%) than other racial/ethnic groups (12%/8%, p&lt;0.001).

Conclusions: In a large, diverse, contemporary sample of early-stage breast cancer patients accrued from population-based registries and linked to clinical laboratory data, one-quarter had genetic testing, with multigene panels markedly replacing BRCA1/2-only tests over time. The ratio of uninformative VUS to informative pathogenic mutation results was lowest in women at high pre-test risk and highest among racial/ethnic minorities. These findings can inform genetic counseling and they emphasize the urgent need to re-classify VUS results in racial/ethnic minorities. More research is needed to determine the impact of this marked increased in multigene panel testing on patient experiences, and the impact of test results on treatment decision-making and outcomes.

Citation Format: Kurian AW, Katz SJ. Trends and results of BRCA1/2 and multigene panel testing in newly diagnosed breast cancer patients [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P4-06-07.