A molecular perspective: Racial disparities in uterine serous carcinoma (085)

Abstract

<b>Objectives:</b> Endometrial cancer (EMCA) is the most common gynecologic malignancy, with deaths disproportionately affecting Black patients. Black patients are more likely to present with advanced-stage uterine serous carcinoma (USC). While socioeconomic differences across racial groups contribute to disparity in endometrial cancer outcomes, genetic and molecular alterations play important roles. <b>Methods:</b> Patients with endometrial adenocarcinoma who received tumor FoundationOne CDx testing at our institution between January 2017 and July 2021 were identified. Genomic alterations, demographic and clinical characteristics were collected. Genes examined were those with a greater than 15% alteration rate among serous tumors. Descriptive statistics and Fisher's exact test were used to analyze data. <b>Results:</b> A total of 162 patients with advanced or recurrent endometrial adenocarcinoma were referred for FoundationOne Cdx testing. Of these, 27.7% (45 of 162) had USC. The remaining tumors included endometrioid (37.7%), carcinosarcoma (17.3%), mixed (8%), clear cell (5.6%), dedifferentiated (2.5%) and undifferentiated (0.6%) carcinomas. Among patients with serous carcinomas, 21 (46.7%) were Black, 16 (35.6%) were White, three (6.7%) were Asian, and five (11.1%) were from other races. Hispanics represented 8.9% (<i>n</i>=4) of patients. Among USC, <i>CCNE1</i> amplification occurred more often in Black patients than in White patients (38.1% vs 0%, p<0.05), while <i>PTEN</i> mutations occurred less frequently (4.7% vs 31.75%, p=0.09). No differences in frequency of <i>TP53, ERBB2/3, FBXW7, PPP2R1A,</i> or <i>PIK3CA</i> alterations were noted among races (Table 1). Among patients with <i>CCNE1</i> amplification, 62.5% (5 of 8) progressed on first-line platinum-based therapy. Co-amplification of <i>ERBB2</i> and <i>CCNE1</i> occurred in three Black patients. Two patients progressed while receiving primary Trastuzumab, and one patient continued to receive upfront therapy. <b>Conclusions:</b> Black patients constituted almost 50% of patients with USC and had an increased frequency of <i>CCNE1</i> amplification. Evaluation in a larger prospective cohort is needed to confirm these molecular differences. The development of new targeted therapies, an active investigation area, will need to keep these alterations at the forefront as trials are being designed.