HER2/EGFR in Cancer Research Open access Peer reviewed

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

Widyanti Soewoto, Ida Bagus Budhi S. A., Wibisono, Kristanto Yuli Yarso and 1 more

Frontiers in Oncology | Sep 10, 2026

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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.

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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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Authors

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Widyanti Soewoto

first | Sebelas Maret University

Ida Bagus Budhi S. A.

middle | Sebelas Maret University

Wibisono

middle | Sebelas Maret University

Kristanto Yuli Yarso

middle | Sebelas Maret University | ORCID 0000-0003-4514-4676

Joko Wibowo Sentoso

last | Sebelas Maret University

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Citation

BibTeX

@article{Soewoto2026Survival,
  title = {Survival disparities in HER2-low versus HER2-positive breast cancer: a systematic review of progression-free survival and overall survival},
  author = {Widyanti Soewoto and Ida Bagus Budhi S. A. and Wibisono and Kristanto Yuli Yarso and Joko Wibowo Sentoso},
  journal = {Frontiers in Oncology},
  year = {2026},
  doi = {10.3389/fonc.2026.1839945},
  url = {https://doi.org/10.3389/fonc.2026.1839945}
}

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