Comprehensive analysis of HER2 Low Breast Cancer Response to Neoadjuvant Chemotherapy, a Retrospective Cohort Study

Abstract

Background: This study aimed to identify the response and survival outcomes of HER2-low patients following neoadjuvant chemotherapy (NAC).

Method: A retrospective cohort of patients who received NAC in the Department of Breast Surgery at Peking Union Medical College Hospital (PUMCH) from September 27, 2016, to January 23, 2024, was reviewed. Multivariate logistic regression and Cox proportional hazards models were used to identify factors associated with pathological complete response (pCR) and survival outcomes. The Kaplan-Meier method was applied to compare survival outcomes between HER2-zero and HER2-low patients.

Result: Four hundred and twenty-one patients meeting the inclusion criteria. The pCR rate of HER2-zero patients was significantly higher than that of HER2-low patients after adjusting for confounders (OR = 2.83, 95% CI: 1.44-5.65, adjusted P = .003). HER2-low patients demonstrated the most stable status after NAC within the hormone receptor (HR)-positive subset (80.82%) and the most unstable status within the HR-negative subset (57.69%). HER2-zero status was associated with worse disease-free survival (DFS) (HR = 1.94, 95% CI: 1.13-3.32, adjusted P = .02), but not with overall survival (OS) (HR = 1.18, 95% CI: 0.59-2.37, P = .65). HER2-zero patients had significantly worse DFS than HER2-low patients in the entire cohort (P = .014) and the HR-positive subset (P < .001). pCR could serve as a surrogate endpoint of favorable survival outcomes for HER2-zero patients, but not for HER2-low patients.

Conclusion: HER2-low patients might exhibit distinct characteristics compared with HER2-zero patients following NAC. Further multicenter, prospective studies are warranted to validate the conclusions of this exploratory research and assess whether HER2-low expression could serve as a new clinical subtype for evaluating NAC treatment outcomes.

Keywords: HER2 low; HER2 status change; neoadjuvant chemotherapy sensitivity; pathological complete response; survival analysis.