predicting which patients get the most benefit from herceptin based chemptherapy
 

Research-Based PAM50 Subtype Predictor Identifies Higher Responses and Improved Survival Outcomes in HER2-Positive Breast Cancer in the NOAH Study

1. Aleix Prat1,2,
2. Giampaolo Bianchini4,
3. Marlene Thomas5,
4. Anton Belousov5,
5. Maggie C.U. Cheang7,
6. Astrid Koehler5,
7. Patricia Gómez1,
8. Vladimir Semiglazov8,
9. Wolfgang Eiermann6,
10. Sergei Tjulandin9,
11. Mikhail Byakhow10,
12. Begoña Bermejo3,
13. Milvia Zambetti4,
14. Federico Vazquez1,
15. Luca Gianni4, and
16. José Baselga1,11

+ Author Affiliations

1. 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

1. 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

• Note: Supplementary data for this article are available at Clinical Cancer Research Online (http://clincancerres.aacrjournals.org/).

• Received January 25, 2013.
• Revision received October 8, 2013.
• Accepted October 9, 2013.

• ©2014 American Association for Cancer Research.

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