Functional subtyping with BluePrint 80-gene profile to identify distinct triple-positive subtypes with and without trastuzumab/chemosensitivity.

Systemic Therapy
Session Type and Session Title: 
Oral Abstract Session A
Poster Session A: Risk Assessment, Prevention, Early Detection, Screening, and Local/Regional Therapy
Abstract Number: 


Poster Board Number: 
Poster Session A Board #C5
J Clin Oncol 33, 2015 (suppl 28S; abstr 114)
Pat W. Whitworth, Peter D. Beitsch, Michael C. Rotkis, James V. Pellicane, Mary Murray, Paul Baron, Carrie L. Dul, Angela Marie Mislowsky, Charles H. Nash, Paul D. Richards, Laura A. Lee, Lisette Stork, Femke De Snoo, Sarah Untch, Mark Gittleman, Stephanie Akbari, Jennifer Beatty; NRG Oncology/NSABP, ALLIANCE/ACOSOG, and Nashville Breast Center, Nashville, TN; Dallas Surgical Group, Dallas, TX; Northern Indiana Cancer Research Consortium, South Bend, IN; Virginia Breast Center, Bon Secours Cancer Institute, Richmond, VA; Akron General Medical Center, Akron, OH; Cancer Specialists of Charleston, Charleston, SC; Great Lakes Management Spclsts, Grosse Pointe Park, MI; Coastal Carolina Breast Center, Murrells Inlet, SC; The Longstreet Clinic PC, Gainesville, GA; Oncology and Hematology Association of Southwest Virginia, Salem, VA; Comprehensive Cancer Center, Palm Springs, CA; Agendia, Amsterdam, Netherlands; Agendia, Irvine, CA; Breast Care Specialists, Allentown, PA; Virginia Hospital Center Reinsch Pierce Family Center for Breast Health, Arlington, VA; The Breast Place, Charleston, SC

Abstract Disclosures


Background: Classification by molecular subtype can aid in the selection of therapy for patients with breast cancer. However at present, the methodology for molecular subtyping is not standardized. The aim of the prospective NBRST study is to compare chemosensitivity as defined by pathological Complete Response (pCR) using the 80-gene BluePrint (BP) functional subtype profile vs. conventional IHC/FISH subtyping. Methods: The study includes women aged 18–90 with histologically proven breast cancer, written informed consent, no excision biopsy or axillary dissection, and no prior therapy for breast cancer. Neo-adjuvant Chemotherapy (NCT) was at the discretion of the physician adhering to NCCN approved or other peer-reviewed regimens. BP in combination with MammaPrint classifies patients into 4 molecular subgroups: Luminal A, Luminal B, HER2 and Basal. Results: 721 patients had definitive surgery. 58/335 (17%) IHC/FISH HR+/HER2- patients were re-classified by BP as Basal (57) or HER2 (1). 92/222 (41%) IHC/FISH HER2+ patients were re-classified as BP Luminal (67) or BP Basal (25). 7/164 (4%) IHC/FISH triple negative (TN) patients were re-classified as BP Luminal (5) or BP HER2 (2). NCT pCR rates were 3% in Luminal A and 9% in Luminal B patients versus 10% pCR in IHC/FISH luminal patients. The NCT pCR rate was 54% in BP HER2 patients. This is significantly superior (p = 0.02) to the pCR rate in IHC/FISH HER2+ patients (40%). BP Basal and IHC/FISH TN had a pCR rate of 35%. Functional BP subtyping divided the 137 IHC/FISH triple positive patients into two major subgroups: BP Luminal (n = 66, pCR = 11%) and BP HER2 (n = 60, pCR = 45%).11 patients were re-classified as BP Basal with pCR = 45%. Conclusions: Molecular subtyping using BP leads to a reclassification of 23% of tumors. The re-classification is most prominent in classically assessed triple positive patients where 48% of patients are re-assigned to the less responsive BP Luminal-type group vs. 44% of patients assigned to the responsive BP HER2-type group. These findings confirm the more accurate identification of molecular subgroups for treatment decision by BluePrint functional subtype classifier. Clinical trial information: NCT01479101