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  • Review Article
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HER2-positive breast cancer is lost in translation: time for patient-centered research

Key Points

  • Since the development of hormonal therapies for breast cancer, the discovery that 20% of breast cancers harbour HER2 amplification and can be effectively treated with trastuzumab underscores impressive science and clinical progress

  • The hope to move from 'stratified' oncology to truly 'personalized' oncology has not yet materialized for HER2-positive breast cancer, despite over a decade of very intensive translational research efforts

  • The failure to address patients' needs regarding treatment options, such as more or less aggressive chemotherapy, longer or shorter anti-HER2 therapy, is an alarming signal

  • Multiple potential biomarkers have been studied in advanced-stage and early-stage disease, including HER2; other relevant growth factor receptors, signalling cascades, the tumour microenvironment, heterogeneity and host factors are being explored

  • HER2 positivity remains the only validated biomarker today in the clinic

  • There is an urgent need to move from highly fragmented translational research towards broader and more-comprehensive collaborative efforts with earlier data sharing and focus on answering questions of true clinical relevance

Abstract

No biomarker beyond HER2 itself, which suffers from a low positive predictive value, has demonstrated clinical utility in breast cancer, despite numerous attempts to improve treatment tailoring for the growing number of anti-HER2 targeted therapies. This prompted us to examine the body of evidence, using a systematic approach, to identify putative predictive biomarkers in HER2-positive breast cancer, and discuss the hitherto failure to address the needs of patients. In the future, it is hoped immune-based biomarkers will predict benefit from anti-HER2 treatments in the neoadjuvant and adjuvant settings. In advanced-stage disease, the quantification of tumour heterogeneity using molecular-imaging technology has generated informative data on the success or failure of the antibody-drug conjugate T-DM1. Treatment tailoring remains a high priority, in cost-constrained health-care systems, but such tailoring will require a dramatic shift in the way translational research is being conducted, with the establishment of large, easily accessible, and well-annotated databases of candidate predictive biomarkers. Single-centre biomarker research should become a thing of the past.

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Figure 1: A schematic representation of the HER2 signalling pathway.

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I.G. G.G. and M.P-G. wrote the manuscript, and all authors reviewed and/or edited the manuscript before submission.

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Correspondence to Martine Piccart-Gebhart.

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Gingras, I., Gebhart, G., de Azambuja, E. et al. HER2-positive breast cancer is lost in translation: time for patient-centered research. Nat Rev Clin Oncol 14, 669–681 (2017). https://doi.org/10.1038/nrclinonc.2017.96

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