Impact of targeted therapy on progression-free survival in breast cancer: A decade of evidence from randomized and clinical trials

Targeted therapies have transformed breast cancer management by focusing on molecular drivers such as HER2 amplification, hormone receptor signaling, and CDK4/6 pathways. They aim to increase disease control while reducing systemic toxicity compared to conventional chemotherapy. This review assessed the effectiveness and safety of targeted therapies in advanced and metastatic breast cancer, with progression-free survival (PFS) as the primary outcome and overall survival (OS), objective response rate (ORR), and safety as secondary endpoints. We systematically searched PubMed/MEDLINE and the Cochrane Library between January 2015 and March 2025 for randomized controlled trials and large clinical studies comparing conventional and targeted pharmacotherapy in breast cancer. Eligible studies reporting progression-free survival were included. PRISMA guidelines were strictly followed. Data extraction and risk-of-bias assessments were performed independently by two reviewers. We included 15 trials with more than 10,000 patients. In HER2-positive disease, trastuzumab deruxtecan (T-DXd) significantly improved PFS and OS compared with trastuzumab emtansine, while tucatinib combinations provided strong intracranial control. CDK4/6 inhibitors (ribociclib, palbociclib, abemaciclib) consistently extended PFS in HR+/HER2– populations across pre- and postmenopausal groups. For triple-negative breast cancer, atezolizumab plus nab-paclitaxel improved outcomes in PD-L1–positive patients. Safety profiles were distinct, with interstitial lung disease from T-DXd, hematologic toxicity from CDK4/6 inhibitors, and immune-related events with checkpoint inhibitors. Targeted therapies substantially improve PFS, with OS benefits in several trials, setting new standards across breast cancer subtypes. Balancing efficacy with toxicity management and improving global access remain essential to maximize clinical benefit.