Abstract P017: Early detection of ovarian cancer in high-risk individuals using circulating miRNAs: The MiDe study

Abstract

Abstract Background: Epithelial ovarian cancers generally carry a poor prognosis due to late-stage presentation and a high rate of disease recurrence. In contrast, diagnosis of early-stage disease is associated with a high rate of durable remission. Prior studies using archival samples have suggested that a neural network analysis of circulating miRNA expression levels may be an informative biomarker for early-stage ovarian cancer diagnosis. Methods: The miRNA Detection Study (MiDe Study) is a prospective, observational clinical trial open to individuals in all 50 U.S. states. Persons with at least one ovary classified as being at high-risk for ovarian cancer, either due to known genetic predisposition or family history suggestive of possible hereditary breast and ovarian cancer syndrome or Lynch syndrome, are eligible to enroll. Study subjects will submit a blood sample every 6 months for up to 5 years. Neural network analysis of serum miRNA profiles will be correlated with the subsequent diagnosis of ovarian cancer or serous tubal intraepithelial carcinoma, either clinically or at the time of risk-reducing salpingectomy or salpingo-oophorectomy. The primary outcomes are the sensitivity and specificity of the neural network for anticipating a diagnosis of epithelial ovarian cancer or a cancer precursor within 2 years of the index blood sample. The goal recruitment is 1000 study subjects. Based on a presumed cancer incidence of 0.5-1% per year among this population, approximately 25 incident cancers or precursors are expected to be diagnosed over the timespan of the study. Results: Enrollment began in September 2019. As of August 1, 2022, 372 subjects had consented to the study. Among study subjects, 270/372 (72.5%) carry a known mutation in BRCA1/2, 63/372 (16.9%) carry a known mutation in a different high-risk gene (e.g., PALB2, BRIP1), and 39/372 (10.5%) are considered high-risk due to a mutation in a gene potentially related to ovarian cancer (e.g., ATM, CHEK2) or based on family history alone. To date, 215 (57.8%) participants have contributed at least one sample, among whom 90/215 (41.9%) of subjects have contributed multiple blood samples. Among the study subjects who have given a sample, 2/215 (0.9%) have been later diagnosed with ovarian cancer. Conclusions: The MiDe Study seeks to establish the feasibility of a circulating miRNA-based test for early diagnosis of epithelial ovarian cancer among high-risk individuals. The results of this study will clarify the performance of the neural network test among a high-risk population and inform subsequent interventional trials. Citation Format: Kevin M. Elias, Dipanjan Chowdhury, Judy Garber, Ryan C. Buehler. Early detection of ovarian cancer in high-risk individuals using circulating miRNAs: The MiDe study. [abstract]. In: Proceedings of the AACR Special Conference: Precision Prevention, Early Detection, and Interception of Cancer; 2022 Nov 17-19; Austin, TX. Philadelphia (PA): AACR; Can Prev Res 2023;16(1 Suppl): Abstract nr P017.