Systematic review reveals divergent survival trajectories between HER2-low and HER2-positive breast cancer, highlighting the need for tailored treatment sequencing with antibody-drug conjugates.
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.
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