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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 
Citation
 BREAST CANCER RESEARCH AND TREATMENT, Vol.184(3) : 743-753, 2020-12 
Journal Title
BREAST CANCER RESEARCH AND TREATMENT
ISSN
 0167-6806 
Issue Date
2020-12
MeSH
Biomarkers, Tumor / genetics ; Breast Neoplasms* / drug therapy ; Breast Neoplasms* / genetics ; Female ; Humans ; Phosphatidylinositol 3-Kinases / genetics ; Prognosis ; Quinazolines ; RNA, Messenger / genetics ; Receptor, ErbB-2 / genetics
Keywords
HER2+metastatic breast cancer ; Intrinsic molecular subtype ; Genetic alteration ; Prediction model
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 ofHER2(OR 14.43;p = 0.001) and copy number(CN) amplification ofHER2(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 betweenPIK3CAalteration and HER2-E subtype (p = 0.655). In terms of drug efficacy, high mRNA expression ofHER2was 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 highHER2mRNA expression withoutPIK3CAgenetic 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.
Full Text
https://link.springer.com/article/10.1007/s10549-020-05891-0
DOI
10.1007/s10549-020-05891-0
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Sohn, Joo Hyuk(손주혁) ORCID logo https://orcid.org/0000-0002-2303-2764
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/189903
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