Nationwide Trends and Determinants of Germline BRCA1/2 Testing in Patients With Breast and Ovarian Cancer

Abstract

Background: Germline genetic testing (GT) for BRCA1/2 is instrumental in identifying patients with breast and ovarian cancers who are eligible for PARP inhibitors (PARPi). Little is known about recent trends and determinants of GT since PARPi were approved for these patients.

Patients and methods: We performed a retrospective cohort study of patients in a nationwide electronic health record (EHR)-derived oncology-specific database with the following GT eligibility criteria: breast cancer diagnosed at age ≤45 years, triple-negative breast cancer diagnosed at age ≤60 years, male breast cancer, or ovarian cancer. GT within 1 year of diagnosis was assessed and stratified by tumor type. Multivariable log-binomial regressions estimated adjusted relative risks (RRs) of GT by patient and tumor characteristics.

Results: Among 2,982 eligible patients with breast cancer, 56.4% underwent GT between January 2011 and March 2020, with a significant increase in GT over time (RR, 1.08; 95% CI, 1.05-1.11, for each year), independent of when PARPi were approved for BRCA1/2-mutated metastatic breast cancer in January 2018. In multivariable analyses, older age (RR, 0.93; 95% CI, 0.90-0.96, for every 5 years) and Medicare coverage (RR, 0.69; 95% CI, 0.49-0.96 vs commercial insurance) were associated with less GT. Among 5,563 eligible patients with ovarian cancer, 35.4% underwent GT between January 2011 and March 2020, with a significant increase in GT over time (RR, 1.11; 95% CI, 1.07-1.14, for each year) that accelerated after approval of PARPi for BRCA1/2-mutated, chemotherapy-refractory ovarian cancer in December 2014 (RR, 1.42; 95% CI, 1.19-1.70). Older age (RR, 0.95; 95% CI, 0.93-0.97, for every 5 years) and Black or African American race (RR, 0.80; 95% CI, 0.65-0.98 vs White race) were associated with less GT.

Conclusions: GT remains underutilized nationwide among patients with breast and ovarian cancers. Although GT has increased over time, significant disparities by age, race, and insurance status persist. Additional work is needed to design, implement, and evaluate strategies to ensure that all eligible patients receive GT.

Keywords: Ovarian cancer; breast cancer; germline genetic testing; guideline adherence.

Figure 1.

Prevalence of germline BRCA1/2 testing over time, estimated using spline regressions among patients with breast cancer (blue) and ovarian cancer (red). Germline BRCA1/2 testing was defined as occurring within one year of diagnosis. Dashed lines indicate 95% confidence intervals.

Figure 2.

Kernel density plot of time from diagnosis to BRCA1/2 test result among patients with breast cancer (blue) and ovarian cancer (red). The dashed red line indicates a threshold of 365 days that was used in subsequent analyses.

Figure 3.

Determinants of germline BRCA1/2 testing within one year of diagnosis among patients with A) breast cancer and B) ovarian cancer. Adjusted relative risks were estimated using log-binomial regressions using the multiply imputed datasets (primary analysis) and in sensitivity analyses limiting to the post-PARP inhibitor approval period, restricting to community oncology practices, limiting to patients who remained alive one year after diagnosis, and using the non-imputed dataset. Generalized estimating equations were used to account for clustering by practice site.

Figure 3.

Determinants of germline BRCA1/2 testing within one year of diagnosis among patients with A) breast cancer and B) ovarian cancer. Adjusted relative risks were estimated using log-binomial regressions using the multiply imputed datasets (primary analysis) and in sensitivity analyses limiting to the post-PARP inhibitor approval period, restricting to community oncology practices, limiting to patients who remained alive one year after diagnosis, and using the non-imputed dataset. Generalized estimating equations were used to account for clustering by practice site.