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Challenges translating breast cancer gene signatures into the clinic

Nature Reviews Clinical Oncology volume 9, pages 58–64 (2012)Cite this article

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Abstract

The advent of microarray-based gene-expression profiling a decade ago raised high expectations for rapid advances in breast cancer classification, prognostication and prediction. Despite the development of molecular classifications, and prognostic and predictive gene-expression signatures, microarray-based studies have not yielded definitive answers to many of the questions that remain germane for the successful implementation of personalized medicine. There are a lack of robust signatures to predict benefit from specific therapeutic agents and it is still not possible to predict prognosis or chemotherapy treatment response in specific disease subsets accurately, such as triple-negative breast cancer. We discuss the hurdles in the development and validation of molecular classification systems, and prognostic and predictive signatures based on microarray gene-expression profiling. We suggest that similar challenges are likely to be encountered in translating next-generation sequencing data into clinically useful information. Finally we highlight strategies for the development of clinically useful molecular predictors in the future.

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Figure 1: Challenges for the development of microarray-based gene signatures to predict drug response.
Figure 2: Generation of predictive markers.

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Acknowledgements

B. Weigelt is funded by a Cancer Research UK postdoctoral fellowship. L. Pusztai is funded in part by the Breast Cancer Research Foundation. A. Ashworth and J. S. Reis-Filho are funded in part by Breakthrough Breast Cancer, Cancer Research UK and Stand-Up to Cancer/American Association for Cancer Research. We thank William Foulkes for his insightful comments. J. S. Reis-Filho is a recipient of the 2010 CRUK Future Leaders Prize. We acknowledge NHS funding to the NIHR Biomedical Research Centre. The study sponsors had no involvement in the design of this Perspective, the literature review, data interpretation, writing of the manuscript or the decision to submit it for publication.

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Authors and Affiliations

  1. Signal Transduction Laboratory, Cancer Research UK London Research Institute, 44 Lincoln's Inn Fields, London, WC2A 3LY, UK

    Britta Weigelt

  2. Department of Breast Medical Oncology, MD Anderson Cancer Center, University of Texas, PO Box 301439, Houston, 77230-1439, TX, USA

    Lajos Pusztai

  3. The Breakthrough Breast Cancer Research Centre, Institute of Cancer Research, 237 Fulham Road, London, SW3 6JB, UK

    Alan Ashworth & Jorge S. Reis-Filho

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  1. Britta Weigelt
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B. Weigelt and J. S. Reis-Filho contributed to the data research, discussion, writing, reviewing and editing of the manuscript. L. Pusztai and A. Ashworth contributed to the discussion, reviewing and editing the manuscript.

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Correspondence to Jorge S. Reis-Filho.

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Weigelt, B., Pusztai, L., Ashworth, A. et al. Challenges translating breast cancer gene signatures into the clinic. Nat Rev Clin Oncol 9, 58–64 (2012). https://doi.org/10.1038/nrclinonc.2011.125

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