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01-12-2020 | Breast Cancer | Clinical trial

Clinical implications of HER2 mRNA expression and intrinsic subtype in refractory HER2-positive metastatic breast cancer treated with pan-HER inhibitor, poziotinib

Authors: Ji-Yeon Kim, Kyunghee Park, Seock-Ah Im, Kyung Hae Jung, Joohyuk Sohn, Keun Seok Lee, Jee Hyun Kim, Yaewon Yang, Yeon Hee Park

Published in: Breast Cancer Research and Treatment | Issue 3/2020

Abstract

Introduction

We explored clinical implication of intrinsic molecular subtype in human epidermal growth factor receptor 2 (HER2) + metastatic breast cancer (BC) with pan-HER inhibitor from a phase II clinical trial of poziotinib in refractory HER2+BC patients.

Methods

For this translational research correlated with phase II clinical trial, we performed an nCounter expression assay, using gene panel including 50 genes for PAM50 prediction and targeted deep sequencing.

Results

From 106 participants, we obtained 97 tumor tissues and analyzed gene expression in 91 of these samples. Of 91 HER2+BCs, 40 (44.0%) were HER2-enriched (E) intrinsic molecular subtype, 17 (18.7%) of Luminal A, 16 (17.6%) of Basal-like, 14 (15.4%) of Luminal B and 4 (4.4%) of Normal-like. HER2-E subtype was associated with hormone receptor negativity (odds ratio [OR] 2.93; p = 0.019), 3 + of HER2 immunohistochemistry(IHC) (OR 5.64; p = 0.001), high mRNA expression of HER2 (OR 14.43; p = 0.001) and copy number(CN) amplification of HER2 (OR 12.80; p = 0.005). In genetic alterations, alteration was more frequently observed in HER2-E subtype (OR 3.84; p = 0.022) but there was no association between PIK3CA alteration and HER2-E subtype (p = 0.655). In terms of drug efficacy, high mRNA expression of HER2 was the most powerful predictor of poziotinib response (median progression-free survival [PFS): 4.63 months [high] vs. 2.56 [low]; p < .001). In a combination prediction model, median PFS of intrinsic subtypes except Her2-E with high HER2 mRNA expression without PIK3CA genetic alteration was 6.83 months and that of the remaining group was 1.74 months (p < .001).

Conclusion

HER2-E subtype was associated with hormone receptor status, HER2 IHC, CN and mRNA expression and TP53 mutation. In survival analysis, the information of level of HER2 mRNA expression, intrinsic molecular subtype and PI3K pathway alteration would be independent predictors to poziotinib treatment.

ClinicalTrials.gov identifier: NCT02418689.

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Title: Clinical implications of HER2 mRNA expression and intrinsic subtype in refractory HER2-positive metastatic breast cancer treated with pan-HER inhibitor, poziotinib
Authors: Ji-Yeon Kim
Kyunghee Park
Seock-Ah Im
Kyung Hae Jung
Joohyuk Sohn
Keun Seok Lee
Jee Hyun Kim
Yaewon Yang
Yeon Hee Park
Publication date: 01-12-2020
Publisher: Springer US
Keywords: Breast Cancer
Breast Cancer
Published in: Breast Cancer Research and Treatment / Issue 3/2020
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI: https://doi.org/10.1007/s10549-020-05891-0

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