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Taxane benefit in breast cancer—a role for grade and chromosomal stability

Nature Reviews Clinical Oncology volume 10, pages 357–364 (2013)Cite this article

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Abstract

Chromosomal instability, which is a characteristic of many human cancers, contributes to intratumour heterogeneity and has been functionally implicated in resistance to taxane therapy in tumour models. However, defining the status of tumour chromosomal instability in a given tumour to test this hypothesis remains challenging. Measurements of numerical and structural chromosomal heterogeneity demonstrate that histological grade correlates with chromosomal instability in oestrogen receptor (ER)-positive breast cancer. Using data on adjuvant taxane therapy in women with breast cancer, we propose that patients with low-grade ER-positive tumours, which are thought to be chromosomally stable, might derive unexpected benefit from taxane therapy. We discuss the implications of the relationships between tumour grade, chromosomal instability and intratumour heterogeneity, the development of high-throughput methods to define tumour chromosomal instability and the potential use of chromosomal instability to tailor therapy.

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Figure 1: Pathways of chromosomal instability.

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Acknowledgements

The authors would like to acknowledge Judith Bliss (Cancer Research UK Section of Clinical Trials, The Institute of Cancer Research, Sutton, UK), David Endesfelder (Helmholtz Zentrum München, Neuherberg, Germany), Nicolai Birkbak (Centre for Biological Sequence Analysis, Technical University of Denmark, Lyngby, Denmark), Ian O. Ellis (University of Nottingham, Department of Histopathology, Nottingham City Hospital, Nottingham, UK), Andy Hanby (Leeds Institute of Molecular Medicine, St James's University Hospital, Leeds, UK), Ian Tomlinson (Wellcome Trust Centre for Human Genetics, Oxford, UK), Maik Kschischo (University of Applied Sciences, Mathematics and Techniques, Remagen, Germany), Janina Kulka (2nd Department of Pathology, Semmelweis University, Budapest, Hungary), Zoltan Szallasi (Centre for Biological Sequence Analysis, Technical University of Denmark, Lyngby, Denmark), Andrea L. Richardson (Dana–Farber Cancer Institute, Boston, USA), Andrew Rowan (Translational Cancer Therapeutics Laboratory, Cancer Research UK, London Research Institute, London, UK) and members of the TRANS–TACT consortium for helpful advice during preparation of the manuscript. The authors would also like to acknowledge Rebecca Burrell and Nicholas McGranahan for help in preparing the article figure. C. Swanton is supported by the Breast Cancer Research Foundation, Medical Research Council UK and Cancer Research UK.

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Authors and Affiliations

  1. Cancer Research UK Section of Clinical Trials, The Institute of Cancer Research, 15 Cotswold Road, Belmont, Sutton, SM2 5NG, UK

    Roger P. A'Hern & Stephen R. D. Johnston

  2. Translational Cancer Therapeutics Laboratory, Cancer Research UK, London Research Institute, 44 Lincoln's Inn Fields, London, WC2A 3LY, UK

    Mariam Jamal-Hanjani & Charles Swanton

  3. 2nd Department of Pathology, Semmelweis University, Üllo˝i u. 93, Budapest, 1091, Hungary

    A. Marcell Szász

  4. Department of Pathology, Memorial Sloan–Kettering Cancer Center, 1275 York Avenue, New York, 10065, NY, USA

    Jorge S. Reis-Filho

  5. Barts Cancer Institute, Queen Mary University of London, Charterhouse Square, London, EC1M 6BQ, UK

    Rebecca Roylance

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  1. Roger P. A'Hern
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Contributions

R. P. A'Hern and M. Jamal-Hanjani contributed equally to the preparation of the manuscript. R. P. A'Hern, M. Jamal-Hanjani, J. S. Reis-Filho and C. Swanton researched the data for the article and wrote the manuscript. All authors contributed to a discussion of the article's content and edited the manuscript before submission.

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Correspondence to Roger P. A'Hern or Charles Swanton.

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Supplementary Box 1

Calculating the number needed to treat with taxane-based chemotherapy to save one breast cancer death (DOC 32 kb)

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A'Hern, R., Jamal-Hanjani, M., Szász, A. et al. Taxane benefit in breast cancer—a role for grade and chromosomal stability. Nat Rev Clin Oncol 10, 357–364 (2013). https://doi.org/10.1038/nrclinonc.2013.67

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