Abstract P5-01-02: Identification and validation of a serum microRNA panel for detection of early-stage breast cancer

Background: Survival outcomes of breast cancer patients can be significantly improved by early detection and treatment. Implementation of mammogram-based screening has significantly improved early detection of breast cancer in the west. However, the use of screening mammography is less prevalent in Asia partly due to social and cultural reasons. The aim of this study was to determine if a serum microRNA (miRNA) panel could be used as blood-based biomarkers to assist in the early detection of breast cancer. Methods: We carried out a multi-center, multi-ethnic study to identify and validate miRNA biomarkers for the early detection of breast cancer. A total of 1042 subjects including 540 breast cancer cases (predominantly stage 1 and 2 cases) and 502 matched controls from 6 independent sources were included in this study. Among these, there were 750 American and European subjects recruited by biobanks and 292 Singaporean Asian Subjects recruited at the National Cancer Centre Singapore and the National University Hospital. The study was conducted in 3 phases in which sera of 289 European Caucasian serum samples (Discovery Cohort) were first interrogated to identify differentially expressed miRNAs between early-stage breast cancer cases and matched controls among 520 circulating miRNA candidates by quantitative RT-PCR using MiRXES assays. The remaining 753 subjects from 5 independent sources were assigned into two groups for biomarker optimization/algorithm development (Optimization Cohort, n=374) and validation (Validation Cohort, n=379). Results: Among the 520 circulating miRNAs measured, 241 were quantified in absolute copy numbers for 289 subjects in the Discovery Cohort. Thirty-three candidate miRNAs were identified. These miRNAs consistently showed differential expression between cancer and control subjects in the Optimization Cohort. A multi-variant panel of 8 miRNAs and an algorithm was developed using the Discovery and Optimization Cohort, with an AUC of 0.981 and 0.918 respectively. When validated in the independent Validation Cohort, the panel demonstrated an AUC of 0.915. Conclusion: We developed and validated a serum miRNA panel that is both sensitive (72.2 - 77.4%) and specific (90.2 - 91.5%) in detecting early stage of breast cancer in both Caucasian and Asian populations. Citation Format: Lihan Zhou, Ruiyang Zou, Sau Yeen Loke, Mikael Hartman, Patrick C.K Goo, Ann S.G. Lee-Lim, Heng-Phon Too. Identification and validation of a serum microRNA panel for detection of early-stage breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-01-02.