HER2 and ESR1 mRNA expression levels and response to neoadjuvant trastuzumab plus chemotherapy in patients with primary breast cancer

Introduction: Recent data suggest that benefit from trastuzumab and chemotherapy might be related to expression of HER2 and estrogen receptor (ESR1). Therefore, we investigated HER2 and ESR1 mRNA levels in core biopsies 
Introduction: Recent data suggest that benefit from trastuzumab and chemotherapy might be related to expression of HER2 and estrogen receptor (ESR1). Therefore, we investigated HER2 and ESR1 mRNA levels in core biopsies of HER2-positive breast carcinomas from patients treated within the neoadjuvant GeparQuattro trial.
Methods: HER2 levels were centrally analyzed by immunohistochemistry (IHC), silver in-situ hybridization (SISH) and qRT-PCR in 217 pretherapeutic formalin-fixed, paraffin-embedded (FFPE) core biopsies. All tumors had been HER2-positive by local pathology and had been treated with neoadjuvant trastuzumab/ chemotherapy in GeparQuattro.
Results: Only 73% of the tumors (158 of 217) were centrally HER2-positive (cHER2-positive) by IHC/SISH, with cHER2-positive tumors showing a significantly higher pCR rate (46.8% vs. 20.3%, p<0.0005). HER2 status by qRT-PCR showed a concordance of 88.5% with the central IHC/SISH status, with a low pCR rate in those tumors that were HER2-negative by mRNA analysis (21.1% vs. 49.6%, p<0.0005). The level of HER2 mRNA expression was linked to response rate in ESR1-positive tumors, but not in ESR1-negative tumors. HER2 mRNA expression was significantly associated with pCR in the HER2-positive/ESR1-positive tumors (p=0.004), but not in HER2-positive/ESR1-negative tumors.
Conclusions: Only patients with cHER2-positive tumors - irrespective of the method used - have an increased pCR rate with trastuzumab plus chemotherapy. In patients with cHER2-negative tumors the pCR rate is comparable to the pCR rate in the non-trastuzumab treated HER-negative population. Response to trastuzumab is correlated to HER2 mRNA levels only in ESR1-positive tumors. This study adds further evidence to the different biology of both subsets within the HER2-positive group. 
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Author:Carsten Michael Denkert, Jens Huober, Sibylle Loibl, Judith Prinzler, Ralf Kronenwett, Silvia Darb-Esfahani, Jan C. Brase, Christine Solbach, Keyur Mehta, Peter Andreas Fasching, Bruno V. Sinn, Knut Engels, Mattea Reinisch, Martin-Leo Hansmann, Hans Tesch, Gunter von Minckwitz, Michael Untch
URN:urn:nbn:de:hebis:30:3-289362
DOI:http://dx.doi.org/10.1186/bcr3384
ISSN:1465-542X
ISSN:1465-5411
Pubmed Id:http://www.ncbi.nlm.nih.gov/pubmed?term=23391338
Parent Title (English):Breast cancer research
Publisher:BioMed Central
Place of publication:London
Document Type:Article
Language:English
Year of Completion:2013
Date of first Publication:2013/02/07
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2013/04/26
Volume:15
Issue:R11
Pagenumber:12
HeBIS PPN:338206663
Institutes:Medizin
Dewey Decimal Classification:610 Medizin und Gesundheit
Sammlungen:Universitätspublikationen
Licence (German):License LogoCreative Commons - Namensnennung 2.0

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