Statistical independence in primary analyses Our main analysis examined baseline (pre-neoadjuvant chemotherapy) HER2 status as a predictor of a pathologic complete response and survival. This status was determined from a single pretreatment core biopsy per patient, yielding independent observations for a single outcome. Standard logistic regression and Cox models are thus appropriate, representing the established approach for pretreatment biomarker analyses in neoadjuvant trials.2-4 In addition, post-neoadjuvant chemotherapy HER2 status was not included in pathologic complete response models in our study. Dr. Chen's within-patient correlation critique and simulation apply to repeated-outcome measures, not our design. Absence of immortal time bias All patients completed planned neoadjuvant chemotherapy without distant metastasis or death and reached surgery according to inclusion criteria. According to the NeoSTEEP (new Standardized Definitions for Efficacy End Points) standard,5 survival time zero was set at the surgery date. This eliminates guaranteed survival time. Reporting standards compliance Our methods detailed centrally confirmed HER2 assessment, categorization, and adjustments, fully complying with STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) guidelines.6 Dr Chen's cluster-level, repeated-outcomes simulation is inapplicable to our single-observation pretreatment data. The author disclosed no conflicts of interest
Fangmeng Fu (Mon,) studied this question.