Affiliation:
1. Duke University Department of Biostatistics and Bioinformatics
2. Duke Cancer Institute
3. Merck & Co Inc
4. Fudan University Shanghai Cancer Center
5. Chinese Academy of Medical Sciences & Peking Union Medical College
6. St Jude Children's Research Hospital
7. Duke University
8. The Fourth Affiliated Hospital of Hebei Medical University
Abstract
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.
Publisher
Research Square Platform LLC