Prognostic effect of low-level HER2 expression in patients with clinically negative HER2 status.

Assessment of HER2 overexpression using immunohistochemistry (IHC) and/or in situ hybridisation (ISH) for the detection of HER2 amplifications is standard to identify patients for established HER2-directed treatments. Patients with lower HER2 expression levels have recently also become candidates for novel therapies targeting HER2. This study aimed to assess tumour and patient characteristics and prognosis in patients with advanced breast cancer (aBC), relative to low HER2 expression levels. PRAEGNANT is a prospective aBC registry (NCT02338167), focusing on molecular biomarkers. Patients in all therapy lines receiving any kind of treatment are eligible. This analysis includes patients with conventionally HER2-negative aBC. Clinical outcome was compared in the groups with no (IHC score 0) or with low HER2 expression (IHC 1+, or IHC 2+/ISH negative). Low HER2 expression levels in triple-negative aBC patients did not influence progression-free survival. Overall survival appeared poorer in patients with IHC 2+ compared with patients with no HER2 expression in the unadjusted analysis (hazard ratio 2.24, 95% confidence interval 0.1.12-4.47). However, this effect was not maintained in the adjusted analysis. In HER2-negative, hormone receptor-positive patients, low HER2 expression appeared to have no effect on prognosis, neither progression-free survival nor overall survival. We could not demonstrate that HER2 expression at a low level and assessed in clinical routine can differentiate patients into prognostic groups. However, the prevalence of patients with a low expression makes this population interesting for clinical trials with potentially active treatments using HER2 as a target.

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Déclaration de conflit d'intérêts

Conflict of interest statement The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: A.D.H. has received honoraria from Teva, GenomicHealth, Celgene, AstraZeneca, Novartis, Pfizer and Roche; J.E. has received honoraria from AstraZeneca, Daiichi-Sankyo, Eisai, Lilly, Novartis, Pierre Fabre, Roche and Pfizer; M.P.L. has received honoraria from Pfizer, Lilly, Roche, MSD, Hexal, Novartis, AstraZeneca, Eisai, medac and Exact Sciences for advisory boards, lectures and travel support; B.V. has received honoraria from Novartis; F.A.T. has received honoraria from Hexal, Novartis, Tesaro and travel expenses from GSK; F.O. received speaker and consultancy honoraria from Amgen, AstraZeneca, Bayer, BMS, Boehringer, Celgene, Cellex, Chugai, Gilead, Hexal, Ipsen, Janssen-Cilag, Merck, MSD, Novartis, Riemser, Roche, Tesaro and Teva; P.H. received honoraria, unrestricted educational grants and research funding from Amgen, AstraZeneca, Eli Lilly, MSD, Novartis, Pfizer and Roche; H.T. has received honoraria from Novartis, Roche, Celgene, TEVA and Pfizer, and travel support from Roche, Celgene and Pfizer; J.E. has received honoraria from AstraZeneca, Daiichi-Sankyo, Eisai, Lilly, Novartis, Pierre Fabre, Roche and Pfizer; D.L. has received honoraria from Amgen, Eli Lilly, Pfizer, Roche, MSD, Hexal, Novartis, AstraZeneca, TEVA, Celgene, Eisai, and Loreal. M.W. has received speaker honoraria from AstraZeneca, Celgene and Novartis; V.M. has received speaker honoraria from Amgen, AstraZeneca, Daiichi-Sankyo, Eisai, Pfizer, MSD, Novartis, Roche, Teva, Seattle Genetics and consultancy honoraria from Genomic Health, Hexal, Roche, Pierre Fabre, Amgen, ClinSol, Novartis, MSD, Daiichi-Sankyo, Eisai, Lilly, Tesaro and Nektar; E.B. has received honoraria from Novartis, Pfizer, Amgen, Daiichi-Sankyo and onkowissen.de; C.H. has received honoraria from Roche Pharma, Pfizer, AstraZeneca, Novartis and Onkovis; C.M.K. received honoraria from Amgen, Axios, Roche, Teva, Novartis, MSD Sharp & Dohme, Mundipharma, NewCo, Pfizer, Riemser and ZytoService, research grants from Amgen, Axios, Novartis, MSD Sharp & Dohme, NewCo, Pfizer and ZytoService, and travel support from Amgen, Paxman Inc., PharmaMar and Pfizer; R.W. has received honoraria from Amgen, AstraZeneca, Celgene, Daiichi-Sankyo, Esai, Exact Science, Nanostring, GSK, Hexal, Lilly, MSD, Mundipharma, Novartis, Odonate, Pfizer, Pierre Fabre, Riemser, Roche, Sandoz, Seattle Genetics, Tesaro Bio, Teva and Viatris; C.T. has received honoraria from Roche, Daiichi-Sankyo and AstraZeneca; M.U. has received honoraria from Abbvie, Amgen, AstraZeneca, BMS, Celgene, Daiichi-Sankyo, Eisai, Lilly Deutschland, Lilly Int., MSD Merck, Mundipharma, Myriad Genetics, Odonate, Pfizer, PUMA Biotechnology, Roche Pharma, Sanofi Aventis Deutschland, TEVA Pharmaceuticals Ind Ltd, Novartis, Pierre Fabre, Clovis Oncology and Seattle Genetics; P.A.F. received honoraria from Novartis, Pfizer, Roche, Amgen, Celgene, Daiichi-Sankyo, AstraZeneca, Merck-Sharp & Dohme, Eisai, Puma and Teva, his institution conducts research with funding from Novartis and Biontech; W.J. has received honoraria and research grants from Sanofi-Aventis, Novartis, Lilly, Pfizer, Roche, Chugai, AstraZeneca, MSD and Daiichi-Sankyo; T.N.F. has received honoraria from Novartis, Roche, Pfizer, TEVA, Diachii Sankyo, AstraZeneca and MSD; S.Y.B. has received honoraria from Roche Pharma, Novartis, Pfizer, MSD, Teva and AstraZeneca. A.S. has received honoraria from Roche, AstraZeneca, Aurikamed GmbH, Celgene, ClinSol Research GmbH, Connectmedica Sp.Z o.o., Deutsche Gesellschaft für Senologie GmbH, if-kongress management gmbh, I-MED Institute GmbH, Lilly Deutschland GmbH, Medicultus GmbH, med publico GmbH, MSD Sharp & Dohme GmbH, onkowissen.de GmbH, Pfizer GmbH, Schattauer Verlag GmbH, Promedicis GmbH, Tesaro Bio Germany GmbH and W. Zuckschwerdt Verlag GmbH; H.-C.K. has received honoraria from Carl Zeiss Meditec, Theraclion, Novartis, Amgen, AstraZeneca, Pfizer, GSK, SurgVision, Onkowissen and Genomic Health/Exact Sciences, travel support from Tesaro and Daiichi-Sankyo and holds stock of Theraclion and Phaon scientific. All remaining others (A.H., L.H., L.A.W., M.W.B., P.W., D.W.) have declared that they do not have any conflicts of interest.