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Open Access Highly Accessed Research article

Critical research gaps and translational priorities for the successful prevention and treatment of breast cancer

Suzanne A Eccles17*, Eric O Aboagye1, Simak Ali1, Annie S Anderson2, Jo Armes7, Fedor Berditchevski4, Jeremy P Blaydes3, Keith Brennan5, Nicola J Brown6, Helen E Bryant6, Nigel J Bundred5, Joy M Burchell7, Anna M Campbell2, Jason S Carroll9, Robert B Clarke5, Charlotte E Coles34, Gary JR Cook7, Angela Cox6, Nicola J Curtin10, Lodewijk V Dekker11, Isabel dos Santos Silva12, Stephen W Duffy13, Douglas F Easton9, Diana M Eccles3, Dylan R Edwards15, Joanne Edwards14, D Gareth Evans5, Deborah F Fenlon3, James M Flanagan1, Claire Foster3, William M Gallagher16, Montserrat Garcia-Closas17, Julia M W Gee18, Andy J Gescher28, Vicky Goh7, Ashley M Groves8, Amanda J Harvey33, Michelle Harvie5, Bryan T Hennessy20, Stephen Hiscox18, Ingunn Holen6, Sacha J Howell5, Anthony Howell5, Gill Hubbard21, Nick Hulbert-Williams22, Myra S Hunter7, Bharat Jasani18, Louise J Jones13, Timothy J Key23, Cliona C Kirwan5, Anthony Kong23, Ian H Kunkler24, Simon P Langdon24, Martin O Leach17, David J Mann1, John F Marshall13, Lesley Ann Martin17, Stewart G Martin11, Jennifer E Macdougall25, David W Miles7, William R Miller24, Joanna R Morris4, Sue M Moss13, Paul Mullan26, Rachel Natrajan17, James PB O’Connor5, Rosemary O’Connor27, Carlo Palmieri31, Paul D P Pharoah9, Emad A Rakha11, Elizabeth Reed29, Simon P Robinson17, Erik Sahai32, John M Saxton15, Peter Schmid30, Matthew J Smalley18, Valerie Speirs19, Robert Stein8, John Stingl9, Charles H Streuli5, Andrew N J Tutt7, Galina Velikova19, Rosemary A Walker28, Christine J Watson9, Kaye J Williams5, Leonie S Young20 and Alastair M Thompson2*

Author Affiliations

1 Imperial College London, Exhibition Rd, London SW7 2AZ, UK

2 University of Dundee, Perth Road, Dundee DD1 4HN, UK

3 University of Southampton, University Road, Southampton SO17 1BJ, UK

4 University of Birmingham, Edgbaston, Birmingham B15 2TT, UK

5 University of Manchester, Oxford Road, Manchester M13 9PL, UK

6 University of Sheffield, Western Bank, Sheffield S10 2TN, UK

7 Kings College London, Strand, London WC2R 2LS, UK

8 University College London, Gower Street, London WC1E 6BT, UK

9 Cancer Research UK, Cambridge Research Institute/University of Cambridge, Trinity Lane, Cambridge CB2 1TN, UK

10 Newcastle University, Claremont Road, Newcastle upon Tyne NE1 7RU, UK

11 University of Nottingham, University Park, Nottingham NG7 2RD, UK

12 London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 2HT, UK

13 Queen Mary University of London, Mile End Road, London E1 4NS, UK

14 University of Glasgow, University Avenue, Glasgow G12 8QQ, UK

15 University of East Anglia, Earlham Road, Norwich NR4 7TJ, UK

16 University College Dublin, Belfield, Dublin 4, Ireland

17 The Institute of Cancer Research, 15 Cotswold Road, London SM2 5MG, UK

18 University of Cardiff, Park Place, Cardiff CF10 3AT, UK

19 University of Leeds, Woodhouse Lane, Leeds LS2 9JT, UK

20 Royal College of Surgeons Ireland, 123, St Stephen’s Green, Dublin 2, Ireland

21 University of Stirling, Stirling FK9 4LA, UK

22 University of Chester, Parkgate Road, Chester, CH1 4BJ, UK

23 University of Oxford, Wellington Square, Oxford OX1 2JD, UK

24 University of Edinburgh, South Bridge, Edinburgh EH8 9YL, UK

25 National Cancer Research Institute, 407 St John Street, London EC1V 4AD, UK

26 Queen’s University Belfast, University Road, Belfast BT7 1NN, UK

27 University College Cork, College Road, Cork, Ireland

28 University of Leicester, University Road, Leicester LE1 4RH, UK

29 Princess Alice Hospice, West End Lane, Esher KT10 8NA, UK

30 Brighton and Sussex Medical School, University of Sussex, Brighton, East Sussex BN1 9PX, UK

31 The University of Liverpool, Brownlow Hill, Liverpool L69 7ZX, UK

32 London Research Institute, 44 Lincoln’s Inn Fields, London WC2A 3LY, UK

33 Brunel University, Kingston Lane, Uxbridge UB8 3PH, UK

34 Cambridge University Hospitals NHS Foundation Trust, Hills Road, Cambridge CB2 0QQ, UK

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Breast Cancer Research 2013, 15:R92  doi:10.1186/bcr3493

Published: 1 October 2013

Abstract

Introduction

Breast cancer remains a significant scientific, clinical and societal challenge. This gap analysis has reviewed and critically assessed enduring issues and new challenges emerging from recent research, and proposes strategies for translating solutions into practice.

Methods

More than 100 internationally recognised specialist breast cancer scientists, clinicians and healthcare professionals collaborated to address nine thematic areas: genetics, epigenetics and epidemiology; molecular pathology and cell biology; hormonal influences and endocrine therapy; imaging, detection and screening; current/novel therapies and biomarkers; drug resistance; metastasis, angiogenesis, circulating tumour cells, cancer ‘stem’ cells; risk and prevention; living with and managing breast cancer and its treatment. The groups developed summary papers through an iterative process which, following further appraisal from experts and patients, were melded into this summary account.

Results

The 10 major gaps identified were: (1) understanding the functions and contextual interactions of genetic and epigenetic changes in normal breast development and during malignant transformation; (2) how to implement sustainable lifestyle changes (diet, exercise and weight) and chemopreventive strategies; (3) the need for tailored screening approaches including clinically actionable tests; (4) enhancing knowledge of molecular drivers behind breast cancer subtypes, progression and metastasis; (5) understanding the molecular mechanisms of tumour heterogeneity, dormancy, de novo or acquired resistance and how to target key nodes in these dynamic processes; (6) developing validated markers for chemosensitivity and radiosensitivity; (7) understanding the optimal duration, sequencing and rational combinations of treatment for improved personalised therapy; (8) validating multimodality imaging biomarkers for minimally invasive diagnosis and monitoring of responses in primary and metastatic disease; (9) developing interventions and support to improve the survivorship experience; (10) a continuing need for clinical material for translational research derived from normal breast, blood, primary, relapsed, metastatic and drug-resistant cancers with expert bioinformatics support to maximise its utility. The proposed infrastructural enablers include enhanced resources to support clinically relevant in vitro and in vivo tumour models; improved access to appropriate, fully annotated clinical samples; extended biomarker discovery, validation and standardisation; and facilitated cross-discipline working.

Conclusions

With resources to conduct further high-quality targeted research focusing on the gaps identified, increased knowledge translating into improved clinical care should be achievable within five years.