Recent Practice-Changing Studies in the First-Line Treatment of Advanced and Metastatic Breast Cancer

The cancer treatment landscape is rapidly evolving, with several practice-changing studies in breast cancer recently presented at major international oncology congresses. Targeted therapy is gaining momentum as a first-line treatment of metastatic breast cancer. Circulating tumor DNA (ctDNA) already informs treatment selection in hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer. The landmark SERENA-6 and INAVO120 studies investigated selective inhibitors of estrogen receptor and phosphoinositide 3-kinase (PI3K), respectively, each demonstrating clinically meaningful benefits. Meanwhile, antibody-drug conjugates are poised to redefine the first-line strategy in HER2-positive and triple-negative metastatic breast cancer, based on compelling findings from the DESTINY-Breast09, ASCENT-04/KEYNOTE-D19, ASCENT-03 and TROPION-Breast02 trials. This review summarizes the key findings from these pivotal studies and their implication for future clinical practice. PEER REVIEWED ARTICLE **Peer reviewers:** Prof. Dr Rupert Bartsch, Division of Oncology, Medical University of Vienna, Vienna, Austria Dr Ruben Bill, Department of Medical Oncology, Bern University Hospital, Bern, Switzerland PD Dr Cvetka Grašič Kuhar, Institute of Oncology Ljubljana, Slovenija PD Dr Constanze Elfgen, Breast-Center Zurich, Zurich, Switzerland Received on October 21, 2025; accepted after peer review on November 24, 2025; published online on November 28, 2025.