Impact of HER2-low status for patients with early-stage breast cancer and non-pCR after neoadjuvant chemotherapy: A National Cancer Database Analysis

Abstract Purpose To investigate potential differences in pathological complete response (pCR) rates and overall survival (OS) between HER2-low and HER2-zero patients with early-stage hormone receptor (HR)-positive and triple-negative breast cancer (TNBC), in the neoadjuvant chemotherapy setting. Methods We identified early-stage invasive HER2-negative BC patients who received neoadjuvant chemotherapy diagnosed between 2010 and 2018 in the National Cancer Database. HER2-low was defined by immunohistochemistry (IHC) 1 + or 2 + with negative in-situ hybridization, and HER2-zero by IHC0. All the methods were applied separately in the HR-positive and TNBC cohorts. Logistic regression was used to estimate the association of HER2 status with pCR (i.e., ypT0/Tis and ypN0). Kaplan-Meier method and Cox proportional hazards model were applied to estimate the association of HER2 status with OS. Inverse probability weighting and/or multivariable regression were applied to all analyses. Results For HR-positive patients, 70.9% (n = 17,934) were HER2-low, whereas 51.1% (n = 10,238) of TNBC patients were HER2-low. For both HR-positive and TNBC cohorts, HER2-low status was significantly associated with lower pCR rates [HR-positive: 5.0% vs. 6.7%; weighted odds ratio (OR) = 0.81 (95% CI: 0.72–0.91), P < 0.001; TNBC: 21.6% vs. 24.4%; weighted OR = 0.91 (95% CI: 0.85–0.98), P = 0.007] and improved OS [HR-positive: weighted hazard ratio = 0.85 (95% CI: 0.79–0.91), P < 0.001; TNBC: weighted hazard ratio = 0.91 (95% CI: 0.86–0.96), P < 0.001]. HER2-low status was associated with favorable OS among patients not achieving pCR [HR-positive: adjusted hazard ratio = 0.83 (95% CI: 0.77–0.89), P < 0.001; TNBC: adjusted hazard ratio = 0.88 (95% CI 0.83–0.94), P < 0.001], while no significant difference in OS was observed in patients who achieved pCR [HR-positive: adjusted hazard ratio = 1.00 (95% CI: 0.61–1.63), P > 0.99; TNBC: adjusted hazard ratio = 1.11 (95% CI: 0.85–1.45), P = 0.44]. Conclusion In both early-stage HR-positive and TNBC patients, HER2-low status was associated with lower pCR rates. HER2-zero status might be considered an adverse prognostic factor for OS in patients not achieving pCR.