Expanding HRD and BRCA1/2 Testing Could Improve Access to Effective Treatments in Ovarian and Breast Cancer
A real-world study reveals the need for increased homologous repair deficiency and BRCA1/2 testing in patients with ovarian and breast cancers.
Breast cancer, female anatomy: © peterschreiber.media - stock.adobe.com
Increased testing to identify patients with homologous repair deficiency (HRD)-negative or BRCA1/2-positive tumors could expand access to targeted treatments such as PARP inhibitors for those with epithelial ovarian cancer (EOC) or metastatic breast cancer (MBC). Findings from a real-world retrospective study across community health systems were published in JCO Oncology Advances.
Overall, 75% of patients with EOC (n = 1002) were evaluated for HRD, with 29% identified as HRD-positive. Forty-six percent of patients with HER2-negative MBC (n = 1002) received BRCA1/2 testing and it was determined that 11% of patients were BRCA1/2-positive. Investigators determined the prevalence and factors associated with HRD or BRCA1/2 testing and a positive result among patients with EOC or HER2-negative MBC.
Multivariable regression analyses suggested that patients with EOC (n = 2626) harboring low-grade serous tumors were less likely to receive testing than patients with high-grade serous tumors. Further, patients who were non-White and non-Hispanic were more likely to be HRD-positive than patients who were White and non-Hispanic. For patients who were White and Hispanic, 9% were HRD-positive and 8% were HRD-negative.
This pattern continued in the MBC cohort, patients who were non-White, non-Hispanic were less likely to receive testing than patients who were White and non-Hispanic. In addition, patients with triple-negative breast cancer (TNBC) were more likely to be tested than patients with HR–positive tumors.
In both cohorts, younger patients, patients with higher-grade tumors, and patients with better performance status were more likely to be tested, along with patients with TNBC.
Study Details
Patients were selected from a longitudinal database of patients with cancer treated within 5 private not-for-profit highly integrated community health systems across 25 states. Data were collected from over 450 hospitals and over 1300 oncologists.
The EOC cohort evaluated 2626 patients who were diagnosed with epithelial ovarian, primary peritoneal, and/or fallopian tube cancer. The median age of patients in this cohort was 65 years (range, 56-73). Of the 1002 patients eligible for study, 72% were White non-Hispanic, 60% were never smokers, 87% were diagnosed with stage III to IV disease, and 61% were diagnosed with high-grade serous tumors.
In the MBC cohort, 1002 of the total 1142 patients were determined to be eligible. The median age of the evaluable patients was 63 years (range, 54-73). Sixty-five percent were White, non-Hispanic, 58% were never smokers, 74% were initially diagnosed with stage III toIV disease, 72% with invasive ductal carcinoma, and 28% had TNBC.
In the EOC cohort, 75% of patients were tested for HRD. Testing was more common among patients living in the South than in the Midwest, those diagnosed at a younger age (64 years for tested patients vs 69 years for untested patients), and those with high-grade serous tumors.
Among patients who had HER2-negative MBC, 46% received BRCA1/2 testing. Testing was more common among younger patients (59 years for tested patients vs 68 years for untested patients), those diagnosed with TNBC, grade 3 tumors, and those with a more favorable performance status.
Investigators reported that testing increased over the 3-year study period for both cohorts but was considerably higher for patients with EOC than MBC. Among patients with MBC, patients with TNBC were more than twice as likely to be tested than patients with HR-positive tumors. In both cohorts, patients who were older were less likely to receive testing.
To conclude, multiple regression analyses suggested that patients with EOC harboring low-grade serous tumors were less likely to receive testing than patients with high-grade serous tumors and non-White, non-Hispanic patients were more likely to be HRD-positive than White, non-Hispanic patients. Thus, investigators concluded that conducting testing to determine HRD and BRCA1/2 status is underutilized, especially among patients with MBC. Patients with MBC could benefit from treatment with PARP inhibitors, and the limited scope of testing could affect access. They recommended efforts to expand testing, especially among those who are more likely to be HRD-positive or BRCA1/2-mutated.
