The increasing incidence of uterine serous cancers in the elderly and Black women: what molecular markers can guide novel treatment approaches for these patients?

Abstract

<h3>Objectives:</h3> To evaluate rare histologic subtypes of uterine cancer in women older than 70 years of age using four large national databases. <h3>Methods:</h3> Incidence rates were estimated in elderly women diagnosed at age 70+ years old with uterine cancer between 2001 and 2016 from the United States Cancer Statistics (USCS) program after correcting for hysterectomy and pregnancy prevalence from the Behavioral Risk Factor Surveillance System. SEER*Stat and Joinpoint regression were used to calculate the incidence rate (per 100,000) and average annual percent change (AAPC). Data from National Cancer Institute Genomic Data Commons Data Portal including The Cancer Genome Atlas Program (TCGA) were obtained to evaluate genomic features that vary between racial groups. <h3>Results:</h3> There were 206,600 women in the USCS registry with uterine cancer diagnosed at 70+ years old between 2001 and 2016. The incidence of endometrioid endometrial carcinoma increased modestly whereas the incidence of uterine carcinosarcoma remained relatively flat over the 15 year study period. In contrast, the incidence of serous carcinomas rose significantly in each of the elderly age groups: 70-74, 75-79, and 80+ (with an annual percent increase of 5.7%, 5.1% and 4.3%, respectively; P<0.001). Black women diagnosed between 70 and 74 years old had the highest incidence of serous histology (61/100,000), with an annual increase of 7.3% between 2001 and 2016 (P<0.001). Based on current projections, the incidence of serous uterine cancer in Black women between 70 and 74 years will surpass that in endometrioid histology by the year 2030 (Fig. 1). We then evaluated the molecular markers related to targetable novel therapies in Black vs White elderly patients. There were 284 eligible uterine cancer patients diagnosed at >70 year old and 57% of the tumors from Black patients (n=42) expressed TP53 vs 44% from White patients (n=153, P=0.12). In contrast, expression between Black and White women was consistent for HER2 (10% vs 7%; P=0.62), PTEN (33% vs 46%; p=0.13), POLE (7% vs 9%; P=0.68), <i>BRCA1</i> (3% vs 5%; P=0.64), and <i>BRCA2</i> (7% vs 8%; P=0.77), respectively. <h3>Conclusions:</h3> There is a significant increase in serous uterine cancer in elderly BlackBlack patients at an annual rate of 7% that is projected to surpass endometrioid adenocarcinoma within 10 years. Further research must be conducted into potential treatments such as targetable therapies to provide clinical benefit for these patients with overall poorer prognosis.