Critical research gaps and translational priorities for the successful prevention and treatment of breast cancer
Authors: Eccles Suzanne A , Aboagye Eric O , Ali Simak , Anderson Annie S , Armes Jo , Berditchevski Fedor , Blaydes Jeremy P , Brennan Keith , Brown Nicola J , Bryant Helen E , Bundred Nigel J , Burchell Joy M , Campbell Anna M , Carroll Jason S , Clarke Robert B , Coles Charlotte E , Cook Gary JR , Cox Angela , Curtin Nicola J , Dekker Lodewijk V , dos Santos Silva Isabel , Duffy Stephen W , Easton Douglas F , Eccles Diana M , Edwards Dylan R , Edwards Joanne , Evans D Gareth , Fenlon Deborah F , Flanagan James M , Foster Claire , Gallagher William M , Garcia-Closas Montserrat , Gee Julia M W , Gescher Andy J , Goh Vicky , Groves Ashley M , Harvey Amanda J , Harvie Michelle , Hennessy Bryan T , Hiscox Stephen , Holen Ingunn , Howell Sacha J , Howell Anthony , Hubbard Gill , Hulbert-Williams Nick , Hunter Myra S , Jasani Bharat , Jones Louise J , Key Timothy J , Kirwan Cliona C , Kong Anthony , Kunkler Ian H , Langdon Simon P , Leach Martin O , Mann David J , Marshall John F , Martin Lesley Ann , Martin Stewart G , Macdougall Jennifer E , Miles David W , Miller William R , Morris Joanna R , Moss Sue M , Mullan Paul , Natrajan Rachel , O’Connor James PB , O’Connor Rosemary , Palmieri Carlo , Pharoah Paul D P , Rakha Emad A , Reed Elizabeth , Robinson Simon P , Sahai Erik , Saxton John M , Schmid Peter , Smalley Matthew J , Speirs Valerie , Stein Robert , Stingl John , Streuli Charles H , Tutt Andrew N J , Velikova Galina , Walker Rosemary A , Watson Christine J , Williams Kaye J , Young Leonie S , Thompson Alastair M 
Published: 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.