Survival disparities in HER2-low versus HER2-positive breast cancer: a systematic review of progression-free survival and overall survival.

BACKGROUND: The emergence of HER2-low breast cancer as a distinct clinical entity has challenged the traditional binary classification of HER2 status. This systematic review aims to evaluate the disparities in Progression-Free Survival (PFS) and Overall Survival (OS) between HER2-low and HER2-positive breast cancer patients. METHODS: A systematic search was performed across PubMed, Scopus, Cochrane Library, ESMO and ASCO for studies published through January 2026. The Clinical trials and observational studies reporting Progression-Free Survival (PFS) and Overall Survival (OS) with Hazard Ratios (HR) were included. Due to significant clinical and methodological heterogeneity, a formal meta-analysis was deemed inappropriate; consequently, evidence was synthesized qualitatively following the Synthesis Without Meta-analysis (SWiM) guidelines. The protocol was prospectively registered in PROSPERO (CRD420261293004). RESULTS: A total of 536 records were identified; after removing 356 duplicates, 180 were screened, and 10 trials met the inclusion criteria. Preliminary synthesis indicates that HER2-low tumors exhibit distinct survival trajectories compared to HER2-positive cohorts, often influenced by Hormone Receptor (HR) co-expression and the type of targeted therapy received. CONCLUSION: Understanding survival disparities is crucial for optimizing treatment sequencing in the era of antibody-drug conjugates (ADCs). SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/prospero/, identifier CRD420261293004.