Targeting the PI3K/AKT/PTEN Pathway in HR+/HER2- Locally Advanced and Metastatic Breast Cancer

Adam M. Brufsky, MD, PhD, and Erika P. Hamilton, MD, delve into the most clinically significant genomic tests and biomarker assays employed in HR+/HER2- breast cancer, focusing on BRCA mutations, PIK3CA alterations, AKT1 alterations, and PTEN alterations, which play crucial roles in determining prognosis and guiding treatment decisions.

Medical experts share their strategies for choosing initial treatment options for HR+/HER2- locally advanced or metastatic breast cancer, debating the most effective frontline therapies based on clinical trial evidence, while also discussing their aspirations for a new standard of care, and the challenges of managing disease progression.

Key opinion leaders explore the mechanisms of resistance that can develop after endocrine therapy and CDK4/6 inhibitor treatment in HR+/HER2- locally advanced or metastatic breast cancer, emphasizing the uncertain etiology of resistance and current hypotheses, while also examining biomarkers that may predict resistance to CDK4/6 inhibitors and endocrine therapy.

The panel examines how resistance mutations influence the efficacy of subsequent treatment lines and delves into the process of selecting later-line therapies based on next-generation sequencing results.

Erika P. Hamilton, MD, discusses the CAPItello-291 trial, which investigated the combination of capivasertib and fulvestrant in advanced HR+, HER2- locally advanced or metastatic breast cancer and led to its FDA approval, emphasizing the improved progression-free survival observed in patients with PIK3CA, AKT1, and PTEN alterations.

Key opinion leaders discuss other clinical trials, including the EMERALD study, and targeted therapies for the treatment of HR+/HER2- locally advanced or metastatic breast cancer in later lines of therapy.

Medical experts address the challenges of managing adverse events in the treatment of HR+/HER2- locally advanced or metastatic breast cancer.

Adam M. Brufsky, MD, PhD, and Erika P. Hamilton, MD, share their perspectives on the future landscape of HR+/HER2- locally advanced or metastatic breast cancer treatment and provide essential insights to summarize the key points of their discussion.