Redefining breast cancer treatment by precision oncology: the clinical impact of sacituzumab govitecan

INTRODUCTION: Trophoblast cell-surface antigen-2 (Trop-2) is overexpressed in most breast cancers, including about 90% of triple-negative breast cancers (TNBC) and more than half of hormone receptor-positive/HER2-negative (HR+/HER2-) tumors, with limited expression in normal tissues, making it an attractive therapeutic target. Sacituzumab govitecan (SG), the first Trop-2-directed antibody-drug conjugate (ADC) delivers the topoisomerase I inhibitor SN-38 to cancer cells and has changed the treatment of metastatic breast cancer (mBC). AREAS COVERED: This review synthesizes data from chemical characterization, pharmacokinetic studies, and the clinical evidence from phases I-III in metastatic TNBC and HR+/HER2- mBC (IMMU-132-01, ASCENT, ASCENT-03, ASCENT-04, ASCENT-07, TROPiCS-02) and in early-stage disease. A literature search from PubMed/MEDLINE, Embase, Scopus and ClinicalTrials.gov, complemented by the proceedings of the ASCO, ESMO and SABCS meetings, was performed up to September 2026 using the terms 'sacituzumab govitecan,' 'Trop-2,' 'antibody-drug conjugates' and 'breast cancer'. EXPERT OPINION: The high drug-to-antibody ratio, membrane-permeable payload and bystander effect of SG explain both its efficacy and its hematological and gastrointestinal toxicity. Its place among the growing family of Trop-2-directed and topoisomerase I payload ADCs will depend on rational sequencing, biomarkers of resistance, and combination with immunotherapy and poly ADP-ribose polymerase inhibitors.