Additional file 1: Table S1. of Biomarker analysis of the NeoSphere study: pertuzumab, trastuzumab, and docetaxel versus trastuzumab plus docetaxel, pertuzumab plus trastuzumab, or pertuzumab plus docetaxel for the neoadjuvant treatment of HER2-positive breast cancer

Biomarker analyses on the intent-to-treat population: sample sizes and technical success rates. *As a percentage of the ITT population (N = 417). CR concentration ratio, Cyt cytoplasmic, EGF epidermal growth factor, EGFR epidermal growth factor receptor, ELISA enzyme-linked immunosorbent assay, FISH fluorescence in situ hybridization, IGF1R insulin-like growth factor 1 receptor, IHC immunohistochemistry, Mem membranous, Nuc nuclear, PIK3CA gene encoding phosphoinositide 3-kinase catalytic subunit, PTEN phosphatase and tensin homolog, qRT-PCR quantitative reverse transcription PCR, sHER2 serum HER2 extracellular domain, SNP single nucleotide polymorphism, TGF transforming growth factor. Table S2. Baseline levels of all biomarkers in all four treatment groups (biomarker population, based on the intent-to-treat population). CR concentration ratio, Cyt cytoplasmic, EGF epidermal growth factor, EGFR epidermal growth factor receptor, ELISA enzyme-linked immunosorbent assay, FISH fluorescence in situ hybridization, IGF1R insulin-like growth factor 1 receptor, IHC immunohistochemistry, Mem membranous, Nuc nuclear, PIK3CA gene encoding phosphoinositide 3-kinase catalytic subunit, PTEN phosphatase and tensin homolog, qRT-PCR quantitative reverse transcription PCR, sHER2 serum HER2 extracellular domain, SNP single nucleotide polymorphism, TGF transforming growth factor. Table S3. Relationship between biomarkers and pCR, adjusted for hormone receptor status and breast cancer type (biomarker population, based on the intent-to-treat population). CR concentration ratio, Cyt cytoplasmic, EGF epidermal growth factor, EGFR epidermal growth factor receptor, ELISA enzyme-linked immunosorbent assay, FISH fluorescence in situ hybridization, IGF1R insulin-like growth factor 1 receptor, IHC immunohistochemistry, Mem membranous, Mut mutant , Nuc nuclear, pCR pathologic complete response, PIK3CA gene encoding phosphoinositide 3-kinase catalytic subunit, PTEN phosphatase and tensin homolog, qRT-PCR quantitative reverse transcription PCR, sHER2 serum HER2 extracellular domain, SNP single nucleotide polymorphism, TGF transforming growth factor, WT wild-type. Cochran–Mantel–Haenszel Chi-square test based on biomarker subgroup x pCR status (2 × 2) stratified by hormone receptor status and breast cancer type. Table S4. Treatment and biomarker interaction tests comparing groups A (trastuzumab plus docetaxel) and B (pertuzumab, trastuzumab, and docetaxel) (median cut-point; biomarker population, based on the intent-to-treat population). *Subgroup defined by using a cutoff for target:centromere ratio of 2. †Subgroup defined using mutation versus no mutation. CR concentration ratio, Cyt cytoplasmic, EGF epidermal growth factor, EGFR epidermal growth factor receptor, ELISA enzyme-linked immunosorbent assay, FISH fluorescence in situ hybridization, IGF1R insulin-like growth factor 1 receptor, IHC immunohistochemistry, Mem membranous, Nuc nuclear, pCR pathologic complete response, PIK3CA gene encoding phosphoinositide 3-kinase catalytic subunit, PTEN phosphatase and tensin homolog, qRT-PCR quantitative reverse transcription PCR, SNP single nucleotide polymorphism, TGF transforming growth factor. Table S5. Relationship between biomarkers and pCR by hormone receptor status (biomarker population, based on the intent-to-treat population). CR concentration ratio, Cyt cytoplasmic, EGF epidermal growth factor, EGFR epidermal growth factor receptor, ELISA enzyme-linked immunosorbent assay, FISH fluorescence in situ hybridization, IGF1R insulin-like growth factor 1 receptor, IHC immunohistochemistry, Mem membranous, Nuc nuclear, pCR pathologic complete response, PIK3CA gene encoding phosphoinositide 3-kinase catalytic subunit, PTEN phosphatase and tensin homolog, qRT-PCR quantitative reverse transcription PCR, sHER2 serum HER2 extracellular domain, TGF transforming growth factor. Table S6. Detailed analyses of biomarker levels by ER status. CR concentration ratio, Cyt cytoplasmic, EGF epidermal growth factor, EGFR epidermal growth factor receptor, ELISA enzyme-linked immunosorbent assay, FISH fluorescence in situ hybridization, IGF1R insulin-like growth factor 1 receptor, IHC immunohistochemistry, Mem membranous, Nuc nuclear, pCR pathologic complete response, PIK3CA gene encoding phosphoinositide 3-kinase, catalytic subunit; PTEN phosphatase and tensin homolog, qRT-PCR quantitative reverse transcription PCR, sHER2 serum HER2 extracellular domain, TGF transforming growth factor; WT wild-type. Cochran–Mantel–Haenszel Chi-square test based on biomarker subgroup × pCR status (2 × 2) stratified by breast cancer type. (DOCX 59 kb)