Homologous recombination deficiency and survival in ovarian high-grade serous carcinoma by self-reported race.

BACKGROUND

Half of ovarian high-grade serous carcinomas (HGSC) have homologous recombination deficiency (HRD). However, HRD is not well-characterized in Black individuals who experience worse survival after a diagnosis of HGSC. The objective of this study was to characterize ovarian HGSC HRD and examine its association with survival by self-reported race.

METHODS

HRD features were identified using matched tumor-normal whole-exome and RNA sequencing in a HGSC cohort. We calculated age and stage-adjusted hazard ratios (HR) and 95% confidence intervals (CIs) for survival, comparing individuals with a feature to those without, separately by self-reported race.

RESULTS

Any HRD was associated with a 32% reduced risk of death in Black individuals compared with a 62% reduction in White individuals (Black HR=0.68, 95%CI 0.43-1.09; White HR=0.38, 95%CI 0.14-1.04). More of the germline and somatic variants detected among Black individuals were unannotated or variants of uncertain significance (VUS; germline 65% versus 45%; somatic 62% versus 50%, respectively). Black individuals with germline unannotated/VUS were more likely to have tumors with HRD scarring and a first-degree family history of breast or ovarian cancer compared with those without (HRD scar 71.4% versus 49.6%; family history 68.4% versus 34.6%).

CONCLUSIONS

HRD testing informs precision-based medicine approaches that improve outcomes, but a higher proportion of VUS among Black individuals may complicate referral for such care leading to worse outcomes for Black individuals.

IMPACT

Our findings emphasize the importance of recruiting diverse individuals in genomics research and better characterizing VUS.