Results of a tumor profiling study of uterine cancer specimens revealed that African-American women were significantly more likely to have uterine cancer characterized as serous carcinoma as well as a higher frequency of TP53-mutatedendothelial carcinoma compared with white women. These findings were accepted for presentation at the Society of Gynecologic Oncology (SGO) Annual Meeting on Women’s Cancer and released on March 28, 2020.1
In the United States, African-American women have a similar incidence of uterine cancer compared with white women; however, they are approximately twice as likely to die of the disease.2 While the origins of this disparity are likely to be attributable to multiple factors, differences in the molecular landscapes of different subtypes of uterine cancer in these 2 populations may at least partially account for the observed differences in mortality.
In this study, uterine cancer tumor specimens from 124 African-American patients and 138 white patients were profiled using DNA sequencing, RNA sequencing, in situ hybridization, and immunohistochemical analysis, and the uterine cancer subtypes represented were serous carcinoma (112 patients), endometrioid (87 patients), carcinosarcoma (49 patients), and leiomyosarcoma (40 patients).
The African-American and white patients had a similar mean age of approximately 63 years, although endometrioid carcinoma was more common in white patients (P =.0023) whereas serous carcinoma was more common in African-American patients (P =.0001).
Regarding the molecular profiles of these tumor samples, no differences in tumor mutational burden, mismatch repair status, or expression of programmed cell death-ligand 1 (PD-L1) or human epidermal growth factor receptor 2 (HER2) were observed between the 2 patient groups.
African-American patients were significantly more likely than white patients to have disease characterized by serous carcinoma (49% versus 31%; P =.0023). Among the identified molecular alterations with significantly higher frequencies in tumor specimens from African-American patients compared with white patients in the subgroup of tumors collectively representing epithelial carcinomas (ie, endometrioid carcinoma, serous carcinoma, and carcinosarcoma) were TP53 mutations (76% versus 54%; P =.0004). Endometrioid carcinoma tumor specimens from African-American patients were also significantly more likely than those from white patients to have mutations in NF1, NFE2L2, MRE11, SETD2, FANCE, PRDM1, and DNMT3A.
In contrast, endometrioid carcinoma was more common in white patients compared with African-American patients (42% versus 15%; P <.001), and epithelial carcinoma tumor specimens from white patients were significantly more likely to have mutations in PIK3CA, PTEN, PIK3R1, AKT1 compared with specimens of epithelial carcinoma from African-American patients (60% vs 37%, P =.0007). In the subgroup of tumor specimens representing serous carcinoma, the frequency of BRCA2 mutations was 8% and 0% for white and African-American patients, respectively (P =.0230).
In their concluding remarks, the study authors noted that these results “may have clinical implications” and that “additional studies are needed to explore these findings.”
Read more of Cancer Therapy Advisor‘s coverage of SGO 2020 by visiting the conference page.
References
- Paladugu R, Baca Y, Xiu J, et al. Differences in the molecular landscape of uterine cancer between African American and Caucasian patients. Submitted to: Society of Gynecologic Oncology (SGO) 2020 Annual Meeting on Women’s Cancer. Abstract 13.
- Henley SJ, Miller JW, Dowling NF, et al. Uterine cancer incidence and mortality – United States, 1999-2016. MMWR. 2018; 67:1333-1338.