Implementation of endometrial cancer molecular subtyping into a hybrid community-academic practice.

OBJECTIVES: We sought to confirm utility of our institution's modified Proactive Molecular Risk Classifier for Endometrial Cancer protocol in our daily practice, which includes mismatch repair (MMR), p53, and L1 cell adhesion molecule (L1CAM) immunohistochemistry with in-house next-generation sequencing for POLE, TP53, and CTNNB1. METHODS: We conducted a retrospective review of all patients in our institution who underwent primary endometrial carcinoma resection from the year prior to protocol implementation (PRE; October 1, 2020, to September 30, 2021) through first year of implementation (POST; October 1, 2021, to September 30, 2022) to compare the distribution of molecular and traditional staging factors using GOG-249 criteria to assign clinical risk. RESULTS: In total, 136 of 260 PRE patients were classified as clinically low risk (LR), of whom 31 were MMR deficient. Of the 157 LR POST patients with endometrioid-type carcinoma, 45 were MMR deficient, 5 were POLE mutant, 5 were TP53 mutant, 56 were of no specific molecular profile (NSMP), and 46 did not receive full protocol testing. Of all 79 POST NSMP endometrioid-type cases, 18 were CTNNB1 mutated and 8 showed L1CAM expression. CONCLUSIONS: Our protocol identified 22 (14%) of 157 LR tumors that harbored incipient intermediate- to high-risk molecular aberrations in TP53, CTNNB1, or L1CAM. Moving forward, results of ongoing trials assessing adjuvant therapy decisions based on molecular classification are necessary to confirm protocol utility and identify appropriate modifications.

Associations Between Adverse Childhood Experiences and Stressful Life Events and Health Outcomes in Pregnant and Breastfeeding Women from Diverse Racial and Ethnic Groups.

Background: This study sought to understand the characteristics of racially/ethnically diverse pregnant and breastfeeding women who have experienced adverse childhood experiences (ACEs) and stressful life events (SLEs) and the relationship among ACEs, SLEs, and health outcomes in this population. Materials and Methods: This was a secondary analysis of cross-sectional data from the Family Matters study. The participants in this study were families with children ages 5-9 (N = 1,307) recruited from Minneapolis-St. Paul primary care clinics representing six racial/ethnic backgrounds (White, Black, Native American, Hmong, Somali, Latino). Primary caregivers completed surveys about personal health, parenting styles, resilience, ACEs, and SLEs. Linear and logistic regression models were used to examine the associations between ACEs and SLEs with health outcomes of pregnant and breastfeeding women at the individual level. Results: A total of 123 racially/ethnically diverse women in this study reported being pregnant or currently breastfeeding. Eighty-eight (72%) reported a history of ACEs or SLEs. Those with both ACEs/SLEs reported more depression, economic strain, and a shorter duration of living in the United States. An increase in one reported ACE or SLE was positively associated with self-reported stress, number of reported medical conditions, substance use, self-efficacy, and permissive parenting (all ß coefficients p < 0.05). SLEs independently demonstrated increased predictive probability of severe mental health distress (6.7 percentage points, confidence interval [95% CI: 0.02-0.11; p < 0.01]) and moderate or severe anxiety (7.5 percentage points [95% CI: 0.04-0.11; p < 0.001]). Conclusion: Exposure to ACEs and SLEs appear to have significant impacts on physical health, mental health, and substance use in pregnant racially/ethnically diverse women.