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Table S1. List of covariates (and associated hazard ratios with 95% CIs as well as P-values) included in the final multivariate regression model applied to evaluate PFS. Final model derived using stepwise backward variable selection. Table S2. PFS in HER2 mRNA and PIK3CA biomarker subgroups. Table S3. PFS in biomarker subgroups defined by PIK3CA in combination with HER2 mRNA expression. Figure S1. PFS by HER2 mRNA expression and PIK3CA biomarker status in patients with de novo disease. (PDF 546 kb)

Supplementary Methods. Treatment â endocrine therapy. Treatment â chemotherapy. Treatment â chemotherapy followed by endocrine therapy. Table S1. Frequency of endocrine therapy. Table S2. Frequency of chemotherapy agent. Table S3. Frequency of chemotherapy followed by endocrine therapy. (DOCX 30 kb)

List of institutional review boards/ethics committees. (PDF 354 kb)

Additional file 1: Table S1. Number of questionnaire responses at each point of assessment. Table S2. Comparison of FACT-Taxane scores of the EG and PG groups during treatment. Table S3. Comparison of Taxane-associated scores of the EG and PG groups during treatment.

Figure S1. Relationship between biomarkers and pCR by treatment group and estrogen receptor 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. (PDF 836Â kb)

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)

Baseline characteristics of patientsâ cohort. Table S2. The relationship among expression levels of ERBB family RTKs in TNBC. Table S3. elationships between stage of disease and chemotherapeutic agent. Table S4. Univariate analysis of baseline characteristics affecting ERBB4 expression (N=203). (DOCX 29 kb)

Box plots for the expression level of HER family genes and ESR1 gene. (A) Training set (N = 203). (B) Validation set (N = 84). (C) Group consisting of non-triple negative breast cancer (N = 52). Figure S2. Relationship among expression of the ERBB family genes and ESR1 gene in TNBC. Figure S3. Survival analysis according to the expression level of ESR1 and ERBB4 expression in the training set. (A) Kaplan-Meier survival curve for stage I/IIA (N = 149). (B) Kaplan-Meier survival curve for stage IIB/IIIA/IIIC (N = 54). (PPTX 266 kb)