Author Contributions: Dr Symmans had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
Study concept and design: Hatzis, Symmans.
Acquisition of data: Pusztai, Valero, Booser, Esserman, Lluch, Vidaurre, Holmes, Souchon, Martin, Cotrina, Gomez, Hubbard, Chacón, Ferrer-Lozano, Dyer, Buxton, Gong, Wu, Ibrahim, Andreopoulou, Ueno, Hunt, Yang, Nazario, DeMichele, Symmans.
Analysis and interpretation of data: Hatzis, Pusztai, Esserman, Wang, Ibrahim, Ueno, Hunt, O’Shaughnessy, Hortobagyi, Symmans.
Drafting of the manuscript: Hatzis, Symmans.
Critical revision of the manuscript for important intellectual content: Hatzis, Pusztai, Valero, Booser, Esserman, Lluch, Vidaurre, Holmes, Souchon, Wang, Martin, Cotrina, Gomez, Hubbard, Chacón, Ferrer-Lozano, Dyer, Buxton, Gong, Wu, Ibrahim, Andreopoulou, Ueno, Hunt, Yang, Nazario, DeMichele, O’Shaughnessy, Hortobagyi, Symmans.
Statistical analysis: Hatzis, Wang.
Obtained funding: Pusztai, Esserman, Symmans.
Administrative, technical, or material support: Pusztai, Valero, Esserman, Lluch, Vidaurre, Holmes, Souchon, Hubbard, Hortobagyi, Symmans.
Study supervision: Pusztai, Valero, Holmes, Souchon, Martin, Gomez, Hortobagyi, Symmans.
Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Hatzis reported holding equity in his employer, Nuvera Biosciences, and holding joint patents with Nuera Biosciences. Dr Pusztai reported serving as an unpaid scientific advisor for Nuvera Biosciences and holding joint patents with Nuera Biosciences. Dr Holmes reported receiving honoraria from Novartis, Genentech, and Philips (with relevance outside the submitted work). Dr Gomez reporting receiving honoraria from GlaxoSmithKline and Bristol-Meyers Squibb (with relevance outside the submitted work). Dr Hortobagyi reported serving as a paid consultant to Allergan, Genentech, Novartis, and sanofi-aventis and receiving research funding from Novartis (with relevance outside the submitted work). Dr Symmans reported serving as an unpaid scientific advisor to Nuvera Biosciences; holding equity in Nuvera Biosciences; holding joint patents with Nuera Biosciences with royalty; and receiving honoraria from Agendia BV.
Funding/Support: This study was supported by grants from Susan G. Komen for The Cure (KG081680) to Dr Symmans; the National Cancer Institute (1 R01 CA106290) to Dr Pusztai; the Breast Cancer Research Foundation to Dr Pusztai and Dr Symmans; the Safeway Foundation to Dr Pusztai and Dr Symmans; faculty funds from Dr Gong, Dr Wu, and Dr Symmans; and generally by the Nellie B. Connally Breast Cancer Research Fund at the M. D. Anderson Cancer Center (MDACC). Additionally, the I-SPY-1 (Investigation of Serial Studies to Predict Your Therapeutic Response With Imaging and Molecular Analysis) trial was supported in part by grants from the National Cancer Institute to the Cancer and Leukemia Group B (Monica M. Bertagnolli, MD, chair [CA31946]) and to the Cancer and Leukemia Group B Statistical Center (Daniel J. Sargent, PhD [CA33601]) and by grants to participating sites: Georgetown University Medical Center, Washington, DC (Minetta C. Liu, MD [CA77597]), Memorial Sloan-Kettering Cancer Center, New York, NY (Clifford A. Hudis, MD [CA77651]), University of California at San Francisco (Charles J. Ryan, MD [CA60138]), University of Chicago, Chicago, Illinois (Hedy L. Kindler, MD [CA41287]), University of Minnesota, Minneapolis (Bruce A. Peterson, MD [CA16450]), University of North Carolina at Chapel Hill (Thomas C. Shea, MD [CA47559]), and University of Texas Southwestern Medical Center, Dallas (Debasish Tripathy, MD [CA37347]).
Role of the Sponsors: The sponsors had no role in the design and conduct of the study; the collection, management, analysis, and interpretation of the data; or the preparation, review, or approval of the manuscript.
Statistical Analysis: Dr Hatzis conducted all analyses for signature development for the discovery cohort. Dr Wang had full access to all data from the validation cohort and conducted independent statistical analyses. Data sets for this study and gene expression weights for signatures are accessible via the GEO repository (http://www.ncbi.nlm.nih.gov/geo/) under accession identification numbers GSE25066 (combined series), GSE25055 (discovery cohort), and GSE25065 (validation cohort).
Disclaimer: The content of this article is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute.
Additional Contributions: We thank the patients who participated in this research and the following colleagues (uncompensated for their contributions) for technical laboratory work in the Department of Pathology: Feng Lin, MS, Bin Zeng, MS, Hongxia Sun, PhD, and Chunxiao Fu, PhD (MDACC Breast Cancer Pharmacogenomics Laboratory); obtaining biopsy samples: Nour Sneige, MD (cytopathology); obtaining clinical data used in this work: Eva Carrasco (Grupo Español de Investigación en Cáncer de Mama), Patricia de los Rios (Lyndon B. Johnson Hospital), Marc Lenburg (Investigation of Serial Studies to Predict Your Therapeutic Response With Imaging and Molecular Analysis), and Chingyi Young, MS, and Anna Kratz (MDACC); and the Departments of Breast Imaging, Pathology, Surgery, and Breast Medical Oncology at MDACC.