TY - JOUR
T1 - Critical research gaps and translational priorities for the successful prevention and treatment of breast cancer
AU - Eccles, Suzanne A.
AU - Aboagye, Eric O.
AU - Ali, Simak
AU - Anderson, Annie S.
AU - Armes, Jo
AU - Berditchevski, Fedor
AU - Blaydes, Jeremy P.
AU - Brennan, Keith
AU - Brown, Nicola J.
AU - Bryant, Helen E.
AU - Bundred, Nigel J.
AU - Burchell, Joy M.
AU - Campbell, Anna M.
AU - Carroll, Jason S.
AU - Clarke, Robert B.
AU - Coles, Charlotte E.
AU - Cook, Gary J.R.
AU - Cox, Angela
AU - Curtin, Nicola J.
AU - Dekker, Lodewijk V.
AU - dos Santos Silva, Isabel
AU - Duffy, Stephen W.
AU - Easton, Douglas F.
AU - Eccles, Diana M.
AU - Edwards, Dylan R.
AU - Edwards, Joanne
AU - Evans, D. G.
AU - Fenlon, Deborah F.
AU - Flanagan, James M.
AU - Foster, Claire
AU - Gallagher, William M.
AU - Garcia-Closas, Montserrat
AU - Gee, Julia M.W.
AU - Gescher, Andy J.
AU - Goh, Vicky
AU - Groves, Ashley M.
AU - Harvey, Amanda J.
AU - Harvie, Michelle
AU - Hennessy, Bryan T.
AU - Hiscox, Stephen
AU - Holen, Ingunn
AU - Howell, Sacha J.
AU - Howell, Anthony
AU - Hubbard, Gill
AU - Hulbert-Williams, Nick
AU - Hunter, Myra S.
AU - Jasani, Bharat
AU - Jones, Louise J.
AU - Key, Timothy J.
AU - Kirwan, Cliona C.
N1 - Funding Information:
We would like to acknowledge the helpful contributions to the final manuscript from the Executive Advisory Board: Kevin Brindle, Robert E Coleman, Charles Coombes, Jack Cuzick, Mitchell Dowsett, Lesley Fallowfield, Christine Friedenreich, William J Gullick, Barry Gusterson, Craig Jordan, Sunil Lakhani, Bettina Meiser, Emma Pennery, Rebecca Riggins and Stephen Johnston. We would also like to acknowledge the contributions of the patient advocate representatives Mairead McKenzie and Marion Lewis from Breast Cancer Care’s Service User Research Panel. SAE acknowledges support from the NIHR RM/ICR Biomedical Research Centre, ICR and Cancer Research UK. AMT acknowledges support from Breast Cancer Campaign, Breakthrough Breast Cancer and CR-UK. Breast Cancer Campaign staff Lisa Wilde, Phyllis Quinn and Stuart Griffiths assisted in the design and implementation of the gap analysis initiative and acted as facilitators throughout the process. Geraldine Byrne was responsible for co-ordinating and delivering the logistics and acted as a facilitator at the nine gap analysis workshops that were held at the Breast Cancer Campaign offices. We thank Dr Alexis Willet who provided editorial assistance on behalf of Punch Consulting.
PY - 2013/10/1
Y1 - 2013/10/1
N2 - 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.
AB - 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.
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U2 - 10.1186/bcr3493
DO - 10.1186/bcr3493
M3 - Article (journal)
C2 - 24286369
AN - SCOPUS:84887563411
SN - 1465-5411
VL - 15
JO - Breast Cancer Research
JF - Breast Cancer Research
IS - 5
M1 - R92
ER -
