Abstract IA009: Racial disparities in high grade endometrial cancers

Abstract

Abstract Endometrial cancer (EC) is the most common gynecological cancer in the United States, with approximately 66,200 cases diagnosed annually. Incidence rates have been increasing over the past two decades, especially in non-white and younger populations. Additionally, population-based studies have shown that the increases are greatest among the more aggressive histologic subtypes. In unadjusted analyses, incidence rates are highest among non-Hispanic white women (NHW); however, when the greater prevalence of hysterectomies in non-Hispanic black women (NHB) is accounted for, the incidence among NHB women exceeds that of other racial and ethnic groups. In addition, survival after an EC diagnosis is significantly lower for NHB women at every stage of diagnosis, and for all histologic subtypes. EC is currently the 6th leading cause of cancer-related deaths among women but will likely overtake ovarian cancer (the 5th leading cause) before the end of the decade—it has already done so for NHB women. Factors influencing survival exist across the cancer care spectrum, starting at diagnosis and continuing through treatment and beyond. A portion of the differences in EC survival can be explained by the histologic subtype of the tumor. Low grade endometrioid ECs are the most common histologic type and tend to have a good prognosis. High grade tumors, such as serous cancers, are more common among NHB women and have poorer prognosis. A better understanding of the molecular characteristics of these more aggressive tumors is warranted, as they are increasing in incidence and cause a disproportionate amount of morbidity and mortality. To date, most studies that have included molecular profiling do not have large enough numbers or participants from diverse populations to examine whether mutations that may be clinically significant differ by race and ethnicity in high grade endometrial cancers. In a population of women with high grade EC (endometrioid, serous, clear cell, mixed) identified from two academic hospitals in Detroit, Michigan, we performed whole exome sequencing on tumor and normal tissue from 285 women. We hypothesized that somatic mutations in specific genes may vary by race and ultimately contribute to the survival disparity consistently identified in population-based studies. We report findings from the two most common high grade histologic subtypes, endometrioid (n=51 NHB, n=60 NHW) and serous (n=85 NHB, n=37 NHW). Established and emerging therapeutic targets were selected as a priori for the initial analysis. Tumor mutational burden (TMB), microsatellite instability status (MSI), mutations in genes in the PIK3 pathway, POLE, ARID1A and p53 were all examined. Findings highlight the need to consider histologic subtype in conjunction with race and ethnicity, as failure to do so may erroneously confound the estimates. Larger studies in diverse populations will be critical to disentangle the contribution of ancestry, histology and somatic mutations to the survival disparities seen after an EC diagnosis. Citation Format: Michele L. Cote. Racial disparities in high grade endometrial cancers [abstract]. In: Proceedings of the AACR Special Conference on Endometrial Cancer: Transforming Care through Science; 2023 Nov 16-18; Boston, Massachusetts. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(5_Suppl):Abstract nr IA009.