Fig 2.

Biomarker analyses of progression-free survival. (A) Significance testing of biomarkers and assays. Assays showing a treatment interaction (P < .4) are shown in blue. The number of patients for whom biomarker data were available for each assay is shown to the left. (B) Hazard ratio estimations by biomarker status for heregulin (HRG), betacellulin (BTC), and human epidermal growth factor receptor 3 (ErbB3) in all patients for whom biomarker data were available. HRG negative (neg), HRG score < 1; HRG positive (pos), HRG score ≥ 1; BTC neg, BTC score < 1; BTC pos, BTC score ≥ 1; ErbB3 low, ErbB3 score < 2; ErbB3 high, ErbB3 score ≥ 2. (C) Local hazard ratio (HR) scan of human epidermal growth factor receptor 2 (HER2) in all patients with available data (blue) or in the subset of these patients who were HRG pos (gold). Local HR was estimated by including all patients with HER2 levels within one standard deviation of the measurement error. The number of patients used for each HR calculation is indicated by the size of the dot. (D) Cumulative HR scans of two-way combinations of biomarkers that passed significance testing by univariable analysis. In the top three plots, cumulative HR was estimated as a function of HER2 threshold, either in all patients for whom biomarker data were available (blue) or in patients positive for the second biomarker (gold; HRG pos, BTC pos, or ErbB3 high [score ≥ 2]). In the bottom three plots, points represent the estimated HR for all patients with available biomarker data (gray), patients positive for one of the biomarkers (blue), or patients positive for both biomarkers (gold). In all six plots, the x-axis indicates the percentage of patients who meet the criteria. Yellow rectangles indicate HR < 0.5. Chr-IHC, chromogenic immunohistochemistry; Fl-qIHC, fluorescence-based quantitative immunohistochemistry; ISH, in situ hybridization; RT-qPCR, reverse-transcriptase quantitative polymerase chain reaction.