Leveraging RNA and synthetic lethality to predict response to treatment in breast cancer (including BRCA-mutated)

Division Of Basic Sciences - Nci

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Linked publications & trials

Abstract

(A) BC-SELECT in Breast Cancer Overall: Major Activities: BC-SELECT was presented at AACR 2024 as a poster. The manuscript is under revision, and the algorithm has been used to guide the research of 1-2 faculty so far. Results: We evaluated BC-SELECT's ability to predict responders to trastuzumab, poly (ADP-ribose) polymerase (PARP) inhibitors, and immunotherapy by tuning on three trials including 86 patients and validating on nine trials including 722 patients. BC-SELECT successfully predicted treatment resposne in all PARP inhibitor studies and immunotherapy studies tested. BC-SELECT significantly distinguished between pCR and non-pCR outcome in 8/9 trials. BC-SELECT also outperformed SELECT and ENLIGHT in predicting immunotherapy response. The algorithm outperformed the original SELECT for immunotherapy prediction in breast cancer. Our findings support ongoing development of BC-SELECT towards potential clinical application, including towards patients with BRCA1-2 driven breast cancers. (B) BC-SELECT in germline BRCA+ breast cancer: Major Activities: We have begun sourcing datasets and reviewing collaborations to establish the efficacy of using BC-SELECT specifically in patients with BRCA1/2+ breast cancer.