Endometrial cancer is the most common gynecologic cancer in the United States. Although the annual incidence rate is slightly lower in African Americans compared to Caucasians, the mortality rate is nearly twice as high. Although racial differences in health care access and delivery have been reported, socioeconomic inequalities only partially account for the poor survival rates. In cooperative group studies of advanced or recurrent endometrial cancer, African Americans have a 25% higher mortality rate, independent of performance status, disease stage, histology and chemotherapy regimen.
Biological differences may underlie the significant racial disparity in the survival of African American women with endometrial cancer. Population-based studies have shown that black women are more likely to be diagnosed with high-grade tumors and advanced stage disease. Non-endometrioid tumors, such as uterine papillary serous (UPSC) or clear cell carcinoma, account for a higher proportion of endometrial cancer deaths among African Americans. Although histologically similar to ovarian serous carcinoma, UPSC is not as sensitive to chemotherapy as first-line treatment or at the time of relapse. Nevertheless, the molecular underpinnings of UPSC may be similar to serous ovarian cancer given their shared M端llerian phenotype. The Cancer Genome Atlas demonstrated widespread copy alterations and p53 mutations in ovarian serous tumors, and others have shown low frequency somatic mutations in over 50% of serous tumors. The goal of our project is to perform high-throughput genomic analysis of UPSC in African American and Caucasian patients to develop a better molecular understanding of this disease, as well as identify potential differences that might explain the disparities in survival by race. We hope the identification of distinct molecular profiles may inform decisions regarding adjuvant therapy for UPSC, and lead to the identification of novel therapeutic targets.