Investigators may have uncovered nearly identical mutations to previously examined patient populations and several notable differences that may be clinically relevant among Black patients with ovarian cancer, according to a recent study published by Lawson-Michod et al in Cancer Research.
Background
High-grade serous ovarian cancer is the most common type of ovarian cancer. Ovarian cancer is often diagnosed in its later stages because of a lack of clear symptoms or an effective screening approach, according to the National Cancer Institute (NCI). More than 12,000 women have been estimated to have died of the disease in 2024.
Extensive federal and private research has been devoted to understanding the causes and optimal treatment regimens for ovarian cancer. The Cancer Genome Atlas is an NCI-initiated genomics database that has characterized the genetic makeup of 33 cancer types.
Study Methods and Results
In the extensive tumor genomic analysis, the investigators used advanced tumor sequencing technology to discern the tumor characteristics of patients aged 20 to 79 who had been diagnosed with high-grade serous ovarian cancer. They then compared their results with those of The Cancer Genome Atlas—in which a majority of the high-grade serous ovarian cancer samples were from White patients—with the goal of understanding whether there were distinctions in the tumors of certain populations given differences in survival.
“Prior characterizations … of mutations in ovarian cancers were done in predominantly White populations,” explained lead study author Kayleigh Lawson-Michod, MPH, PhD, a molecular epidemiologist at the University of Utah. “This project was unique in that it was [one of] the first large studies to characterize tumor mutations in Black [patients] with high-grade serous ovarian cancer,” she added.
“The characterizations between these groups showed similar mutations. But Black [patients] have a 43% 5-year overall survival rate for ovarian cancer compared [with] 51% for all [U.S. patients],” revealed co–senior study author Jen Doherty, MS, PhD, Professor of Population Health Sciences at the University of Utah and Co-Leader of the Cancer Control and Population Sciences Program at the Huntsman Cancer Institute. “Our research shows that this discrepancy is unlikely to be explained by the genetic makeup of the tumors themselves,” she continued.
Nonetheless, the investigators discovered a few key differences. In the analysis of Black patients, KRAS mutations were more prevalent than in White patients.
“KRAS did not show up as a significant mutation in the high-grade serous ovarian cancer patients from [The Cancer Genome Atlas]. However, just because KRAS may be more prevalent in Black [patients] does not mean it is not present in all populations with this cancer type. If validated, this could be a missed treatment opportunity,” highlighted Dr. Lawson-Michod.
Additionally, the investigators found that the Black patients involved in the study had a higher prevalence of homologous recombination deficiency (HRD), which prevents damaged cells from repairing themselves. HRD tumors are sensitive to targeted therapy with PARP inhibitors.
Conclusions
“HRD status is associated with better survival, but Black [patients] have higher mortality rates from this disease than other [patients],” indicated co–senior study author Joellen Schildkraut, PhD, MPH, Professor of Epidemiology as well as a member of the Cancer Prevention and Control Research Program at the Winship Cancer Institute at Emory University. “This characterization of ovarian cancer in an understudied population such as this can hopefully impact clinical decision-making for all women with ovarian cancer and inform targeted treatment for this disease,” she emphasized.
“Our analysis shows the importance of researching different types of populations,” underscored Dr. Doherty. “The molecular features that we discover in one patient group will allow us to find potential targets for drug therapies that will work for all patients and improve ovarian cancer health care for everyone,” she concluded.
Disclosure: The research in this study was supported by the National Institutes of Health/NCI and the Huntsman Cancer Foundation. For full disclosures of the study authors, visit aacrjournals.org.
