NYMC Faculty Publications

Age-Independent Preoperative Chemosensitivity and 5-Year Outcome Determined by Combined 70- and 80-Gene Signature in a Prospective Trial in Early-Stage Breast Cancer


Pat Whitworth, Nashville Breast Center, Nashville, TN, USA.
Peter D. Beitsch, Targeted Medical Education, Cupertino, CA, USA.
James V. Pellicane, Bon Secours Cancer Institute, Richmond, VA, USA.
Paul L. Baron, Breast and Melanoma Specialist of Charleston, Charleston, SC, USA.
Laura A. Lee, Comprehensive Cancer Center, Palm Springs, CA, USA.
Carrie L. Dul, Ascension St. John Hospital Great Lakes Cancer Management Specialists, Grosse Pointe Woods, MI, USA.
Charles H. Nash, Northeast Georgia Medical Center, Gainesville, GA, USA.
Mary K. Murray, Akron General Medical Center, Akron, OH, USA.
Paul D. Richards, Blue Ridge Cancer Center, Roanoke, VA, USA.
Mark Gittleman, Breast Care Specialists, Allentown, PA, USA.
Raye Budway, St. Clair Hospital, Pittsburgh, PA, USA.
Rakhshanda Layeequr Rahman, Texas Tech University, Lubbock, TX, USA.
Pond Kelemen, Ashikari Breast Center, Sleepy Hollow, NY, USA.
William C. Dooley, Breast Institute, University of Oklahoma Health Sciences, Oklahoma City, OK, USA.
David T. Rock, Regional Breast Care, Fort Myers, FL, USA.
Ken Cowan, University of Nebraska Medical Center, Omaha, NE, USA.
Beth-Ann Lesnikoski, The Breast Institute at JFK Medical Center, Atlantis, FL, USA.
Julie L. Barone, Exempla Saint Joseph Hospital, Denver, CO, USA.
Andrew Y. Ashikari, Ashikari Breast Center, Sleepy Hollow, NY, USA.
Beth Dupree, St. Mary Medical Alliance Cancer Specialists, Langhorne, PA, USA.
Shiyu Wang, Agendia Inc., Irvine, CA, USA.
Andrea R. Menicucci, Agendia Inc., Irvine, CA, USA.
Erin B. Yoder, Agendia Inc., Irvine, CA, USA.
Christine Finn, Agendia Inc., Irvine, CA, USA.
Kate Corcoran, Agendia Inc., Irvine, CA, USA.
Lisa E. Blumencranz, Agendia Inc., Irvine, CA, USA.
William Audeh, Agendia Inc., Irvine, CA, USA. william.audeh@agendia.com.

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Annals of Surgical Oncology

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BACKGROUND: The Neoadjuvant Breast Symphony Trial (NBRST) demonstrated the 70-gene risk of distant recurrence signature, MammaPrint, and the 80-gene molecular subtyping signature, BluePrint, precisely determined preoperative pathological complete response (pCR) in breast cancer patients. We report 5-year follow-up results in addition to an exploratory analysis by age and menopausal status. METHODS: The observational, prospective NBRST (NCT01479101) included 954 early-stage breast cancer patients aged 18-90 years who received neoadjuvant chemotherapy and had clinical and genomic data available. Chemosensitivity and 5-year distant metastasis-free survival (DMFS) and overall survival (OS) were assessed. In a post hoc subanalysis, results were stratified by age (≤ 50 vs. > 50 years) and menopausal status in patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) tumors. RESULTS: MammaPrint and BluePrint further classified 23% of tumors to a different subtype compared with immunohistochemistry, with more precise correspondence to pCR rates. Five-year DMFS and OS were highest in MammaPrint Low Risk, Luminal A-type and HER2-type tumors, and lowest in MammaPrint High Risk, Luminal B-type and Basal-type tumors. There was no significant difference in chemosensitivity between younger and older patients with Low-Risk (2.2% vs. 3.8%; p = 0.64) or High-Risk tumors (14.5% vs. 11.5%; p = 0.42), or within each BluePrint subtype; this was similar when stratifying by menopausal status. The 5-year outcomes were comparable by age or menopausal status for each molecular subtype. CONCLUSION: Intrinsic preoperative chemosensitivity and long-term outcomes were precisely determined by BluePrint and MammaPrint regardless of patient age, supporting the utility of these assays to inform treatment and surgical decisions in early-stage breast cancer.