Real-World Outcomes and Clinicopathologic Features of Human Epidermal Growth Factor Receptor 2-Low Breast Cancer in a...

The emergence of targeted therapy for patients with human epidermal growth factor receptor 2 (HER2)-low tumors has transformed treatment paradigms, increasing the relevance of assessing this biomarker. Approximately 60% of patients with breast cancer have HER2-low tumors. This study aims to describe the clinicopathologic characteristics and prognosis of patients with HER2-low.

We conducted a multicenter, retrospective cohort study including patients with breast cancer previously classified as HER2-negative between January 2018 and December 2022. Tumors were reclassified as HER2-0 (immunohistochemistry [IHC] score 0) or HER2-low (IHC score 1+ or 2+ with negative in situ hybridization). Survival outcomes were analyzed using the Kaplan-Meier method with log-rank tests for group comparisons. Univariable and multivariable Cox proportional hazards models were constructed to assess independent prognostic factors. Statistical analyses were performed using STATA version 19.5, and two-sided P values <.05 were considered statistically significant.

A total of 704 patients were included with a median follow-up of 63.1 months. No significant differences in event-free survival (EFS) were observed between HER2-0 and HER2-low patients (P = .139). Overall survival (OS) favored HER2-low over HER2-0 patients (P = .050). HER2-low and estrogen receptor had a marked prognostic impact in EFS (P = .002) and OS (P < .0001).

HER2-low was associated with a modest difference in OS compared with HER2-0 tumors; the borderline statistical significance of this finding should be interpreted cautiously and may not reflect a clinically meaningful effect. Further prospective studies are warranted to validate this observation and explore the potential predictive value of HER2-low status for response to novel directed agents.