Abstract IA25: Development of PI3K inhibitors in breast cancer

Abstract

Abstract The phosphatidylinositol-3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) signaling pathway is crucial to many aspects of cell growth and survival. PI3K pathway is frequently deregulated in breast cancer due to genetic or epigenetic alterations in components of this pathway and contributes to treatment resistance. Notably, PIK3CA mutation is the most frequent genetic event in estrogen receptor-positive (ER+) breast cancer, while loss of PTEN expression is commonly observed in triple-negative disease (TNBC). There has been significant interest in developing PI3K inhibitors in breast cancer. Several randomized clinical trials assessing the benefit of adding PI3K inhibitors to fulvestrant in patients with advanced ER+ breast cancer, including BELLE-2, BELLE-3, FERGI, and SANDPIPER, have been reported. Significant improvement in progression-free survival (PFS) has been observed in these trials. However, dose-limiting toxicities of pan-PI3K inhibitors are common, which limit their clinical application. Isoform selective inhibitors, such as alpha selective PI3K inhibitor, are in clinical trials with the hope to reduce toxicity. There is ongoing effect in the investigation of predictors of response and mechanisms of treatment resistance. This presentation will summarize clinical trial data in breast cancer and challenges in the development of PI3K inhibitors in breast cancer. Citation Format: Cynthia X. Ma. Development of PI3K inhibitors in breast cancer [abstract]. In: Proceedings of the AACR Special Conference on Targeting PI3K/mTOR Signaling; 2018 Nov 30-Dec 8; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Res 2020;18(10_Suppl):Abstract nr IA25.