Germline and somatic genetic testing trends among women with epithelial ovarian cancer (197)

Abstract

Objectives: Identifying homologous recombination deficiency (HRD) mutations has significant treatment implications for women with epithelial ovarian cancer (EOC). While germline testing strategies have been well cataloged in clinical practice, and the American Society for Clinical Oncology recommends somatic testing if germline testing is negative, best-practice strategies for obtaining somatic, germline, or combination testing remain unclear. We aimed to trend rates and temporal relationships of germline and somatic genetic testing at an academic institution to identify gaps in equitable access to precision testing. Methods: All patients with EOC were identified from the electronic medical record (EMR) using diagnostic codes at a single urban academic gynecologic oncology group from January 2015 to December 2020. IRB approval was obtained and an EMR review was performed to analyze trends in germline and somatic genetic testing. Descriptive statistics and Chi-square tests were performed. Results: A total of 431 women with EOC were identified. Patients were predominantly White (88%), older women (mean age 68) who had insurance (97%). Most patients had advanced stage disease (80%) with high-grade serous histology (77%). Eighty percent of patients underwent germline testing with 15% having BRCA1/2 mutations identified. The somatic testing rate was 50% with rates increasing each contact year (Figure 1A) and a detection rate of 29.5% for HRD mutations. Combination testing rates also increased per contact year (Figure 1B). Patients with negative germline testing were more likely to undergo somatic testing (60%) compared to those with germline BRCA1 (29%) or BRCA2 (37%) mutations (p = 0.0012). About 12.5% of patients with negative germline testing had a somatic mutation in either BRCA1/2 or loss of heterozygosity. Of patients without germline genetic testing, only 27% had somatic testing performed (22/81). Thirty percent had somatic testing performed after a recurrence; however, 36% of patients experiencing a recurrence never underwent somatic testing. Sixty-nine percent had somatic testing performed on a current tissue specimen as opposed to archived tissue. Conclusions: Somatic testing resulted in actionable HRD mutations in one in three patients in this cohort, with one in eight patients having somatic HRD mutations despite negative germline testing. This illustrates the therapeutic potential of comprehensive genetic profiling and represents how variations in practice may result in missed therapeutic interventions. As somatic testing rates continue to increase, efforts to define barriers and create streamlined, guideline-based strategies for universal testing are warranted to better align with current clinical practice guidelines. Objectives: Identifying homologous recombination deficiency (HRD) mutations has significant treatment implications for women with epithelial ovarian cancer (EOC). While germline testing strategies have been well cataloged in clinical practice, and the American Society for Clinical Oncology recommends somatic testing if germline testing is negative, best-practice strategies for obtaining somatic, germline, or combination testing remain unclear. We aimed to trend rates and temporal relationships of germline and somatic genetic testing at an academic institution to identify gaps in equitable access to precision testing. Methods: All patients with EOC were identified from the electronic medical record (EMR) using diagnostic codes at a single urban academic gynecologic oncology group from January 2015 to December 2020. IRB approval was obtained and an EMR review was performed to analyze trends in germline and somatic genetic testing. Descriptive statistics and Chi-square tests were performed. Results: A total of 431 women with EOC were identified. Patients were predominantly White (88%), older women (mean age 68) who had insurance (97%). Most patients had advanced stage disease (80%) with high-grade serous histology (77%). Eighty percent of patients underwent germline testing with 15% having BRCA1/2 mutations identified. The somatic testing rate was 50% with rates increasing each contact year (Figure 1A) and a detection rate of 29.5% for HRD mutations. Combination testing rates also increased per contact year (Figure 1B). Patients with negative germline testing were more likely to undergo somatic testing (60%) compared to those with germline BRCA1 (29%) or BRCA2 (37%) mutations (p = 0.0012). About 12.5% of patients with negative germline testing had a somatic mutation in either BRCA1/2 or loss of heterozygosity. Of patients without germline genetic testing, only 27% had somatic testing performed (22/81). Thirty percent had somatic testing performed after a recurrence; however, 36% of patients experiencing a recurrence never underwent somatic testing. Sixty-nine percent had somatic testing performed on a current tissue specimen as opposed to archived tissue. Conclusions: Somatic testing resulted in actionable HRD mutations in one in three patients in this cohort, with one in eight patients having somatic HRD mutations despite negative germline testing. This illustrates the therapeutic potential of comprehensive genetic profiling and represents how variations in practice may result in missed therapeutic interventions. As somatic testing rates continue to increase, efforts to define barriers and create streamlined, guideline-based strategies for universal testing are warranted to better align with current clinical practice guidelines.