Statistical methods
MAY, SECONDARY
pCR rates by treatment arm were assessed across biomarker subgroups for HER2 IHC (IHC1+, IHC2+, or IHC3+), HER2/CEP17 gene ratio (≥ 2 to < 4 or ≥ 4), HER2 and HER3 mRNA expression (≤ median or > median), HER2 staining pattern (focal, heterogeneous, or homogeneous), A multivariate analysis was carried out to identify biomarkers most prognostic for pCR, regardless of treatment. Univariate analysis based on a logistic model was conducted for all biomarkers assessed. Biomarkers showing at least a moderate potential association with pCR (< 0.15 significance level) were included in a multivariate logistic model in which backwards selection was applied. The final analysis model included randomized treatment plus the set of biomarker covariates selected based on the previous step.An unstratified Cox proportional hazards model was used to estimate hazard ratios (HRs) between biomarker subgroups (preplanned: HER2 IHC subgroups [3+ versus 2+], PD-L1 IHC [IC 1/2/3 versus IC 0], and PIK3CA [mutated versus non-mutated]; post hoc: PAM50 subtype [HER2-E versus non-HER2-E]) and corresponding 95% CIs for the EFS endpoint. The Kaplan–Meier approach was used to estimate 3-year EFS rates and corresponding 95% CIs.Changes in PAM50 subtype, PD-L1 IHC status, percentage of stromal TILs, and HER2 mRNA levels (NanoString) from baseline to cycle 2 and surgery were assessed by treatment arm.As these were exploratory analyses, all gene expression levels, HRs, odds ratios, and 95% CIs should be considered descriptive and are included for illustrative purposes only. The clinical cutoff dates for the biomarker analyses were the same as those used for the primary and secondary endpoints: December 3, 2015, for the pCR analysis and May 29, 2018, for the final EFS analysis.