Next-generation sequencing for PTEN testing in HR+/HER2˗ metastatic breast cancer

Abstract

Molecular alterations in the Phosphoinositide 3-kinase (PI3K) pathway are key drivers of tumorigenesis and progression in hormone receptor-positive, HER2-negative (HR+/HER2 −) metastatic breast cancer (MBC). These genomic changes are actionable through targeted therapeutic agents. In particular, access to these therapies depends on accurate molecular testing of PIK3CA, AKT1, and PTEN. Next-generation sequencing (NGS) has emerged as a transformative diagnostic tool, offering a comprehensive analysis of PI3K pathway alterations while concurrently evaluating other actionable markers, such as ESR1 and BRCA. Acknowledging its clinical importance, the European Society for Medical Oncology (ESMO) recommends NGS of tumor or plasma samples as the standard of care for patients with HR+ /HER2 − MBC. Although resource-intensive, NGS represents a significant advancement in MBC diagnostics, ensuring that therapeutic decisions are informed by a detailed and multidimensional molecular profile. This review highlights the capabilities of NGS for PI3K pathway testing in HR+ /HER2 − MBC, with a particular focus on the spectrum of PTEN alterations.