Patient Case and Molecular Profiling in HR+/HER2-Negative Advanced Breast Cancer

Dr. Paolo Tarantino presents a hypothetical case of a 62-year-old postmenopausal woman with hormone receptor-positive, HER2-negative advanced breast cancer. He reviews her initial diagnosis of stage IIB, grade 2 disease and subsequent treatment with surgery, adjuvant chemotherapy, radiation, and 5 years of endocrine therapy. Approximately 2 years after completing adjuvant endocrine therapy, the patient develops metastatic disease involving the bones and mediastinal lymph nodes. She initially responds to an aromatase inhibitor plus a CDK4/6 inhibitor but experiences disease progression after 22 months, with new liver lesions and modest progression of mediastinal lymphadenopathy. At this point, ctDNA testing identifies an activating AKT1 mutation and an ESR1 mutation. Dr. Tarantino discusses the potential value of a liver biopsy to reassess estrogen receptor expression in the setting of new liver metastases. He also highlights the importance of evaluating baseline metabolic risk, including the patient's HbA1c and fasting glucose, when considering subsequent treatment options.