• Aleix Prat, Giampaolo Bianchini, Marlene Thomas, Anton Belousov, Maggie C U Cheang, Astrid Koehler, Patricia Gómez, Vladimir Semiglazov, Wolfgang Eiermann, Sergei Tjulandin, Mikhail Byakhow, Begoña Bermejo, Milvia Zambetti, Federico Vazquez, Luca Gianni, and José Baselga.
• Authors' Affiliations: Translational Genomics Group, Vall d'Hebron Institute of Oncology; Department of Medicine, Universitat Autònoma de Barcelona, Barcelona; Hospital Clinico Universitario, Valencia, Spain; Oncologia Medica, San Raffaele Cancer Centre, Milan, Italy; Roche, Pharma Research and Early Development, Penzberg; Frauenklinik vom Roten Kreuz, Munich, Germany; University of North Carolina, Chapel Hill, North Carolina; NN Petrov Research Institute of Oncology, St Petersburg, Russian Federation; NN Blokhin Russian Cancer Centre; Central Clinical Hospital named after N A Semashko, Moscow, Russia; and Memorial Sloan-Kettering Cancer Center, New York, New York.
• Clin Cancer Res. 2014 Jan 15; 20 (2): 511-21.

PurposeWe 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 DesignGene 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.ResultsHER2-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.ConclusionsAs 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.©2014 AACR.

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