Treatment Selection in PIK3CA-Mutated HR+/HER2-Negative Advanced Breast Cancer

Dr. Jason Mouabbi presents a 59-year-old postmenopausal woman with PIK3CA-mutated HR-positive/HER2-negative advanced breast cancer who develops metastatic disease 8 months after completing adjuvant endocrine therapy. The patient has bone-only metastatic disease, an ECOG performance status of 0, an HbA1c of 5.8%, a BMI of 31, and a family history of type 2 diabetes. Molecular testing at recurrence identifies a PIK3CA mutation, while ESR1 remains wild type and no AKT1 or PTEN alterations are detected. Dr. Mouabbi characterizes the recurrence as secondary endocrine resistance and discusses how the patient's recurrence timing, biomarker profile, disease distribution, performance status, and baseline metabolic characteristics inform treatment selection. He explains why the patient fits the population studied in INAVO120 and discusses treatment with inavolisib in combination with palbociclib and fulvestrant. He also notes the role of a bone-modifying agent in patients with osseous metastatic disease.