Anna DeFazio

Background: Prior studies have examined survival in patients with epithelial ovarian cancer (EOC); however, few consider race and ethnicity, particularly disaggregating Asian and Native Hawaiian/Pacific Islander women. Methods: We analysed data from 18 Ovarian Cancer Association Consortium studies, including women with EOC from Asian ( n = 697), non-Hispanic Black ( n = 267), Hispanic ( n = 492), Native Hawaiian/Pacific Islander ( n = 98) and non-Hispanic White ( n = 12,998) racial and ethnic groups. We ran Cox proportional hazards models estimating overall survival by race and ethnicity, adjusting for age, stage, year of diagnosis, and histotype, with fully adjusted models accounting for body mass index, smoking, and postmenopausal hormone use. We also examined associations between hormone-related factors and family history and overall survival by race and ethnicity, testing for heterogeneity. Results: Compared to non-Hispanic White women with EOC, Native Hawaiian/Pacific Islander and non-Hispanic Black women had poorer overall survival (Hazard Ratios, HR = 1.58, 95% CI = 1.16–2.16, and HR = 1.31, 95% CI = 1.12–1.54, respectively). The association was more pronounced for Native Hawaiian/Pacific Islander women with high-grade serous carcinoma (HR = 2.00, 95% CI = 1.37–2.92). There was no significant heterogeneity in the associations between epidemiological factors and survival by racial and ethnic groups ( p ≥ 0.31). Discussion: Native Hawaiian/Pacific Islander and non-Hispanic Black women with EOC had poorer survival, highlighting the need to address disparities in outcome.

BRCA -associated homologous recombination deficiency (HRD) is present in ~50% of high-grade serous carcinomas (HGSC) and predicts sensitivity to platinum-based therapy. However, there is little understanding of why some patients with BRCA -deficient tumors experience poor outcomes. In a large HGSC cohort (n = 1389) including 282 individuals with pathogenic germline BRCA variants (g BRCA pv), residual disease after primary surgery has limited prognostic effect in g BRCA pv-carriers compared to non-carriers, and prognostic outcomes differ based on the mutation location within functional domains of the BRCA genes. Multi-omic profiling is performed on 154 tumors, enriched for patients with BRCA -deficient tumors that experienced short overall survival ( ≤ 3 years, n = 42). Patients with BRCA2 -deficient HGSC and loss of NF1 survive twice as long as those without NF1 loss, whereas PIK3CA , RAD21 and MYC amplification define BRCA2 -deficient HGSC with exceptionally short survival. Patients with BRCA1 -deficient HGSC and a more elevated HRD score survive significantly longer. BRCA1 -deficient tumors in short survivors have evidence of immunosuppressive c-kit signaling and EMT. Our findings confirm that outcome is not determined by BRCA status alone, but rather a combination of co-occurring genomic alterations, the extent of DNA repair deficiency, and the tumor-immune microenvironment.

Kaplan–Meier curves of OS in (A) main tumor groups (n = 582)—MBOT, MOC, LGI, and UGI; (B) patients with MOC by FIGO stage (n = 184); (C) patients with MOC by pattern of invasion in all stages (n = 178); and (D) patients with stage I MOC (n = 134), by pattern of invasion.

Heat map of unsupervised clustering analysis. Contains all samples with a concordant pathology diagnosis (n = 497), with MOC grouped by FIGO stage. Labels show main clusters and diagnoses. Gene-expression values are normalized and logarithm base 2 transformed. dx, diagnosis.

Associations between gene expression and stage group and OS in MOC.