Research-Based PAM50 Subtype Predictor Identifies Higher Responses and Improved Survival Outcomes in HER2-Positive Breast Cancer in the NOAH Study
- Aleix Prat1,2,
- Giampaolo Bianchini4,
- Marlene Thomas5,
- Anton Belousov5,
- Maggie C.U. Cheang7,
- Astrid Koehler5,
- Patricia Gómez1,
- Vladimir Semiglazov8,
- Wolfgang Eiermann6,
- Sergei Tjulandin9,
- Mikhail Byakhow10,
- Begoña Bermejo3,
- Milvia Zambetti4,
- Federico Vazquez1,
- Luca Gianni4, and
- José Baselga1,11
+ Author Affiliations
- Authors' Affiliations: 1Translational Genomics Group, Vall d'Hebron Institute of Oncology; 2Department of Medicine, Universitat Autònoma de Barcelona, Barcelona; 3Hospital Clinico Universitario, Valencia, Spain; 4Oncologia Medica, San Raffaele Cancer Centre, Milan, Italy; 5Roche, Pharma Research and Early Development, Penzberg; 6Frauenklinik vom Roten Kreuz, Munich, Germany; 7University of North Carolina, Chapel Hill, North Carolina; 8NN Petrov Research Institute of Oncology, St Petersburg, Russian Federation; 9NN Blokhin Russian Cancer Centre; 10Central Clinical Hospital named after N A Semashko, Moscow, Russia; and 11Memorial Sloan-Kettering Cancer Center, New York, New York
- Corresponding Author:
José Baselga, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10065. Phone: 212-639-3201; Fax: 212-794-3182; E-mail: baselgaj@mskcc.org
Abstract
Purpose: We report a retrospective exploratory analysis of the association of the research-based prediction analysis of microarray 50 (PAM50) subtype predictor with pathologic complete response (pCR) and event-free survival (EFS) in women enrolled in the NeOAdjuvant Herceptin (NOAH) trial.
Experimental Design: Gene expression profiling was performed using RNA from formalin-fixed paraffin-embedded core biopsies from 114 pretreated patients with HER2-positive (HER2+) tumors randomized to receive neoadjuvant doxorubicin/paclitaxel (AT) followed by cyclophosphamide/methotrexate/fluorouracil (CMF), or the same regimen in combination with trastuzumab for one year. A control cohort of 42 patients with HER2-negative tumors treated with AT-CMF was also included. The PAM50 subtypes, the PAM50 proliferation score, and the PAM50 risk of relapse score based on subtype (RORS) and subtype and proliferation (RORP) were evaluated.
Results: HER2-enriched (HER2-E) tumors predominated within HER2+ disease, although all PAM50 intrinsic subtypes were identified across the three cohorts. The OR for achieving pCR with trastuzumab-based chemotherapy for HER2+/HER2-E and HER2+/RORP-high were 5.117 (
P = 0.009) and 8.469 (
P = 0.025), respectively, compared with chemotherapy only. The pCR rates of HER2+/HER2-E and HER2+/RORP-high after trastuzumab-based chemotherapy were 52.9% and 75.0%, respectively. A statistically nonsignificant trend was observed for more pronounced survival benefit with trastuzumab in patients with HER2+/HER2-E and HER2+/RORP-high tumors compared with patients with HER2+/non-HER2-E and HER2+/non-RORP-high tumors, respectively.
Conclusions: As determined by EFS and pCR, patients with HER2+/HER2-E tumors, or HER2+/RORP-high tumors, benefit substantially from trastuzumab-based chemotherapy. The clinical value of this genomic test within HER2+ disease warrants further investigation.
Clin Cancer Res; 20(2); 511–21. ©2014 AACR.
Footnotes
- Received January 25, 2013.
- Revision received October 8, 2013.
- Accepted October 9, 2013.
- ©2014 American Association for Cancer Research.
predicting which patients get the most benefit from herceptin based chemptherapy
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