HR-Positive/HER2-Negative Metastatic Breast Cancer: Molecular Testing and Targeted Therapy Selection After Disease Progression

Dr. Adam Brufsky and the panel continue their discussion of treatment sequencing in HR-positive/HER2-negative metastatic breast cancer, focusing on the role of molecular profiling and biomarker-directed therapy following progression on CDK4/6 inhibitor-based treatment. The faculty review emerging clinical data evaluating targeted therapies in patients with alterations in the PI3K/AKT/PTEN pathway and discuss how these findings may influence future treatment strategies. Dr. Rita Nanda, Dr. Rebecca Shatsky, and Dr. Virginia Kaklamani explore practical considerations surrounding genomic testing, including interpretation of next-generation sequencing results, identification of PTEN alterations, and the strengths and limitations of tissue-based versus liquid biopsy approaches. The discussion also addresses challenges in selecting appropriate targeted therapies when molecular alterations are identified and highlights unanswered questions regarding pathway activation and treatment sensitivity. Throughout the conversation, the panel emphasizes the importance of integrating molecular findings with clinical judgment to support individualized treatment decisions and optimize care for patients with HR-positive/HER2-negative metastatic breast cancer.