Research-Based PAM50 subtype predictor identifies higher responses and improved survival outcomes in HER2- Positive breast cancer in the NOAH Study

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, José Baselga

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    121 Citations (Scopus)

    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 trastuzumabbased 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 American Association for Cancer Research.
    Original languageEnglish
    Pages (from-to)511-521
    JournalClinical Cancer Research
    Volume20
    Issue number2
    DOIs
    Publication statusPublished - 15 Jan 2014

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