Racial disparities in high-risk endometrial subtype diagnoses reported

Racial disparities in high-risk endometrial subtype diagnoses reported | Image Credit: © Studio Romantic - © Studio Romantic - stock.adobe.com.

The frequency of CCNE1 amplification is increased among Black patients, according to a recent study published in Frontiers in Oncology.¹

There are significant racial disparities related to endometrial cancer, such as Black patients more often presenting at an advanced stage vs White patients. Additionally, a 2-fold increased risk of breast cancer mortality is reported in Black patients vs White patients, at 8.85 vs 5.70 deaths per 100,000 women, respectively, from 2000 to 2011.

Health care disparities are influenced by social and biological determinants of health. While efforts have been made to adjust for these factors, increased endometrial cancer mortality remains present in Black women.

Tumor next-generation sequencing has significantly improved the understanding of tumor biology. However, data about tumor biology in Black women remains limited by the lack of enrollment of these patients into clinical trials.²

To evaluate molecular tumor profiling among Black patients, investigators conducted a retrospective cohort study.¹ Patients receiving next-generation tumor sequencing at the study institution between January 2017 and August 2022 were included in the analysis.

Immunohistochemical staining, expert pathologist review, and next-generation sequencing were employed to identify histologic subtypes. Commonly altered genes were defined as those with an alteration rate over 15% in the cohort.

Electronic medical records were assessed for demographic and clinical data. This included race and ethnicity, age, stage at diagnosis, insurance status, recurrence history, disease status, and lines of therapy.

The time from the start of therapy to clinical progression or evidence of disease progression was reported as progression free survival. The time from diagnosis to death or last follow-up was used to measure overall survival.

Referral for tumor next-generation sequencing was reported in 289 patients, 26.3% of whom were uterine serous carcinomas, while endometrioid tumors were reported in 39.1% and carcinosarcoma in 19.4%. Under 10% of the cohort had undifferentiated, mixed, clear cell, or dedifferentiated tumors.

Black patients reported 29.4% of endometrial adenocarcinomas, vs 52.6% by White patients. Endometrioid histology was reported in 66.4% of White patients with tumors. Uterine serous carcinoma was more common in Black patients with tumors than White patients, at 38.8% vs 28.2%, respectively.

Patients with uterine serous carcinoma were aged a median 69 years at diagnosis, with most having advanced stage disease. Therapy use, including surgery and adjuvant radiation or chemotherapy, did not significantly differ between Black vs White patients. Death from cancer-related caused was reported in 36.4% of Black patients and 33.3% of White patients.

For tumor next generation sequencing results, TP53, ARID1A, ERBB2/3, FBXW7, MYC, and PPP2R1A alteration rates were similar between racial groups. Black patients had reduced rates of PI3K/AKT/mTOR pathway mutations but higher rates of CCNE1 amplification, at 48.5% and 36.36%, respectively, vs 86.7% and 6.67%, respectively, in White patients.

Progression during first line platinum-based chemotherapy was reported in 40% of patients with CCNE1 amplifications, with 73% progressing within 1 year of diagnosis. The median overall survival was significantly reduced in patients with CCNE1 amplification, at 44.3 months vs 97.3 months in all uterine serous carcinoma patients.

These results indicated an increased risk of high-risk endometrial subtype diagnosis with distinct molecular subtypes in Black patients. Investigators concluded there is a “need to focus on increasing minority enrollment in clinical trials and access to tumor next generation sequencing.”

References

1. Lara OD, Karpel H, Friedman S, Hacker KE, Pothuri B. Race- associated molecular differences in uterine serous carcinoma. Front Oncol. 2024;14:1445128. doi:10.3389/fonc.2024.1445128
2. Scalici J, Finan MA, Black J, Harmon MD, Nicolson W, Lankes HA, et al. Minority participation in gynecologic oncology group (GOG) studies. Gynecol Oncol. 2015;138:441–444. doi:10.1016/j.ygyno.2015.05.014