A'Hern, R. P., Jamal-Hanjani, M., Szasz, A. M., Johnston, S. R. D., Reis, J. S., Roylance, R., Swanton, C. (2013) Taxane benefit in breast cancer-a role for grade and chromosomal stability. NATURE REVIEWS CLINICAL ONCOLOGY, 10 (6). pp. 357-364. ISSN 1759-4774

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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.

Item Type:	Article
Authors (ICR Faculty only):	Ahern, Roger and Johnston, Stephen and Reis-Filho, Jorge
All Authors:	A'Hern, R. P., Jamal-Hanjani, M., Szasz, A. M., Johnston, S. R. D., Reis, J. S., Roylance, R., Swanton, C.
Additional Information:	ISI Document Delivery No.: 152VU Times Cited: 0 Cited Reference Count: 77 A'Hern, Roger P. Jamal-Hanjani, Mariam Szasz, A. Marcell Johnston, Stephen R. D. Reis-Filho, Jorge S. Roylance, Rebecca Swanton, Charles Breast Cancer Research Foundation; Medical Research Council UK; Cancer Research UK 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 Munchen, 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. Nature publishing group New york
Uncontrolled Keywords:	s-phase fraction nuclear-dna content spindle assembly checkpoint in-situ hybridization term follow-up histological grade karyotypic complexity mitotic checkpoint prognostic-significance paclitaxel sensitivity
Research teams:	Closed research groups > Molecular Pathology Clinical Units > Breast Unit ICR divisions > Cancer Therapeutics > Hit Discovery & Structural Design ICR divisions > Structural Biology > Hit Discovery & Structural Design
Depositing User:	Alexander Smithson
Date Deposited:	15 Jul 2013 15:12
Last Modified:	07 May 2014 15:05
URI:	http://publications.icr.ac.uk/id/eprint/12565

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