Molecular Testing in PIK3CA-Mutated HR+/HER2-Negative Advanced Breast Cancer

Dr. Jason Mouabbi discusses the role of molecular testing in guiding treatment selection for patients with PIK3CA-mutated HR-positive/HER2-negative advanced breast cancer. He emphasizes establishing a molecular profile at the onset of metastatic disease to identify actionable alterations that may inform targeted treatment options. Dr. Mouabbi distinguishes alterations that may be present early in tumor development, such as PIK3CA, AKT1, and PTEN alterations, from alterations that may emerge during treatment, including ESR1 and HER2 mutations. He highlights the value of repeat molecular testing at disease progression to identify newly acquired or evolving alterations that may contribute to treatment resistance. The discussion also addresses testing approaches, including tissue-based next-generation sequencing at metastatic diagnosis and the potential use of both tissue and liquid biopsy when tissue is insufficient. For subsequent disease progression, Dr. Mouabbi describes liquid biopsy as a practical approach for reassessing the molecular profile and identifying potentially actionable changes.