Rebecca Shatsky, MD; Rita Nanda, MD; Kelly McCann, MD, PhD; Nusayba Bagegni, MD; and Alexis LeVee, MD,discuss how recent advances in hormone receptor–positive breast cancer treatment, including oral SERDs such as elacestrant, PI3K pathway inhibitors, and antibody-drug conjugates such as T-DXd, are being integrated into clinical practice based on biomarkers such as ESR1 mutations and HER2-low expression while addressing key sequencing decisions and resistance mechanisms in the evolving therapeutic landscape.
Panelists discuss how they will review the latest updates in hormone receptor–positive, HER2-negative, and HER2-low metastatic breast cancer, focusing on oral selective estrogen receptor degraders (SERDs), targeted therapies, and antibody-drug conjugates presented at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting.
Panelists discuss how the SERENA-6 trial design uses circulating tumor DNA (ctDNA) monitoring to detect ESR1 mutations and switch patients from aromatase inhibitors to oral selective estrogen receptor degraders (SERDs) such as camasertinib while continuing CDK4/6 inhibitors.
Panelists discuss how elacestrant from the EMERALD trial is being incorporated into practice based on ESR1 mutation status and duration of prior CDK4/6 inhibitor therapy, with combination approaches being explored in the ELEVATE trial.
Panelists discuss how upcoming oral selective estrogen receptor degraders (SERDs; eg, camasertinib, imlunestrant, and giredestrant) are showing efficacy primarily in populations with ESR1 mutations and are all well-tolerated oral agents that will likely receive approvals.
Panelists discuss how to approach decision-making among PI3K/AKT pathway inhibitors (capivasertib, alpelisib, everolimus) based on mutation status, toxicity profiles, and dosing schedules in the second-line setting.
Panelists discuss how they decide when to transition from endocrine-based therapies to antibody-drug conjugates, considering factors such as endocrine sensitivity, disease burden, and pace of progression.
Panelists discuss how the TROPiCS-02 trial established sacituzumab govitecan for hormone receptor–positive, HER2-negative metastatic breast cancer and how it influences sequencing decisions with other antibody-drug conjugates (ADCs) such as trastuzumab deruxtecan.
Panelists discuss how datopotamab deruxtecan from the TROPHY-PD-01 trial compares with sacituzumab govitecan, highlighting different toxicity profiles and the challenge of sequencing multiple antibody-drug conjugates (ADCs) with the same TROP2 payload.
Panelists discuss how to manage toxicities associated with datopotamab deruxtecan, particularly ocular toxicity and stomatitis, using prophylactic measures such as steroid mouthwash and eye drops.
Panelists discuss how treatment options for HER2-low and HER2-ultralow metastatic breast cancer include trastuzumab deruxtecan (T-DXd) and sacituzumab govitecan, with sequencing becoming a key consideration.
Panelists discuss how subgroup analyses from DESTINY-Breast06 show trastuzumab deruxtecan benefits across different mutation groups, with particularly strong responses in patients with BRCA1/2-mutated disease due to the topoisomerase I inhibitor payload.
Panelists discuss how they approach sequencing decisions for patients with hormone receptor–positive, HER2- low/ultralow disease, emphasizing selective use of trastuzumab deruxtecan in first-line chemotherapy settings while considering quality-of-life factors.
Panelists discuss how HER2 testing challenges for identifying HER2-low and -ultralow expression require coordination with pathologists and may involve
Panelists discuss how the field has made exciting strides, with oral selective estrogen receptor degraders (SERDs) likely moving into early-stage disease and the need for alternative antibody-drug conjugate (ADC) payloads beyond topoisomerase I inhibitors to overcome resistance mechanisms.
