Research-based PAM50 subtype predictor identifies higher responses and improved survival outcomes in HER2-positive breast cancer in the NOAH study.

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.

• Authors: 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
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 20 Issue 2 Pg. 511-21 (Jan 15 2014) ISSN: 1557-3265 [Electronic] United States
• PMID: 24443618 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: ©2014 AACR.

Chemical References

• Antibodies, Monoclonal, Humanized
• Receptors, Estrogen
• Receptors, Progesterone
• Receptor, ErbB-2
• Trastuzumab

Topics

• Adult
• Aged
• Antibodies, Monoclonal, Humanized (administration & dosage)
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Breast Neoplasms (drug therapy, genetics, mortality, pathology)
• Female
• Gene Expression Profiling (methods)
• Humans
• Lymphatic Metastasis
• Middle Aged
• Neoadjuvant Therapy
• Neoplasm Grading
• Neoplasm Staging
• Prognosis
• Receptor, ErbB-2 (genetics, metabolism)
• Receptors, Estrogen (metabolism)
• Receptors, Progesterone (metabolism)
• Retrospective Studies
• Trastuzumab
• Treatment Outcome