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

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

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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.

Original languageEnglish
Article numberR92
Number of pages37
JournalBreast Cancer Research
Volume15
Issue number5
DOIs
Publication statusPublished - 1 Oct 2013

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Translational Medical Research
Breast Neoplasms
Biomarkers
Epigenomics
Breast
Neoplasm Metastasis
Circulating Neoplastic Cells
Therapeutics
Neoplasms
Molecular Epidemiology
Molecular Pathology
Neoplastic Stem Cells
Radiation Tolerance
Computational Biology
Research
Drug Resistance
Cell Biology
Life Style
Molecular Biology
Survival Rate

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Eccles, S. A., Aboagye, E. O., Ali, S., Anderson, A. S., Armes, J., Berditchevski, F., ... Thompson, A. M. (2013). Critical research gaps and translational priorities for the successful prevention and treatment of breast cancer. Breast Cancer Research, 15(5), [R92]. https://doi.org/10.1186/bcr3493

Critical research gaps and translational priorities for the successful prevention and treatment of breast cancer. / 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 J R; Cox, Angela; Curtin, Nicola J; Dekker, Lodewijk V; Silva, Isabel dos Santos; Duffy, Stephen W; Easton, Douglas F; Eccles, Diana M; Edwards, Dylan R; Edwards, Joanne; Evans, D; 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; 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 P B; 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.

In: Breast Cancer Research, Vol. 15, No. 5, R92, 01.10.2013.

Research output: Contribution to journalReview article

Eccles, SA, Aboagye, EO, Ali, S, Anderson, AS, Armes, J, Berditchevski, F, Blaydes, JP, Brennan, K, Brown, NJ, Bryant, HE, Bundred, NJ, Burchell, JM, Campbell, AM, Carroll, JS, Clarke, RB, Coles, CE, Cook, GJR, Cox, A, Curtin, NJ, Dekker, LV, Silva, IDS, Duffy, SW, Easton, DF, Eccles, DM, Edwards, DR, Edwards, J, Evans, D, Fenlon, DF, Flanagan, JM, Foster, C, Gallagher, WM, Garcia-Closas, M, Gee, JMW, Gescher, AJ, Goh, V, Groves, AM, Harvey, AJ, Harvie, M, Hennessy, BT, Hiscox, S, Holen, I, Howell, SJ, Howell, A, Hubbard, G, Hulbert-Williams, N, Hunter, MS, Jasani, B, Jones, LJ, Key, TJ, Kirwan, CC, Kong, A, Kunkler, IH, Langdon, SP, Leach, MO, Mann, DJ, Marshall, JF, Martin, L, Martin, SG, Macdougall, JE, Miles, DW, Miller, WR, Morris, JR, Moss, SM, Mullan, P, Natrajan, R, O'Connor, JPB, O'Connor, R, Palmieri, C, Pharoah, PDP, Rakha, EA, Reed, E, Robinson, SP, Sahai, E, Saxton, JM, Schmid, P, Smalley, MJ, Speirs, V, Stein, R, Stingl, J, Streuli, CH, Tutt, ANJ, Velikova, G, Walker, RA, Watson, CJ, Williams, KJ, Young, LS & Thompson, AM 2013, 'Critical research gaps and translational priorities for the successful prevention and treatment of breast cancer', Breast Cancer Research, vol. 15, no. 5, R92. https://doi.org/10.1186/bcr3493
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 J R ; Cox, Angela ; Curtin, Nicola J ; Dekker, Lodewijk V ; Silva, Isabel dos Santos ; Duffy, Stephen W ; Easton, Douglas F ; Eccles, Diana M ; Edwards, Dylan R ; Edwards, Joanne ; Evans, D ; 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 ; 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 P B ; 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. / Critical research gaps and translational priorities for the successful prevention and treatment of breast cancer. In: Breast Cancer Research. 2013 ; Vol. 15, No. 5.
@article{ebd05d3e19a14f3eaa18bb30573cfd41,
title = "Critical research gaps and translational priorities for the successful prevention and treatment of breast cancer",
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.",
author = "Eccles, {Suzanne A} and Aboagye, {Eric O} and Simak Ali and Anderson, {Annie S} and Jo Armes and Fedor Berditchevski and Blaydes, {Jeremy P} and Keith Brennan and Brown, {Nicola J} and Bryant, {Helen E} and Bundred, {Nigel J} and Burchell, {Joy M} and Campbell, {Anna M} and Carroll, {Jason S} and Clarke, {Robert B} and Coles, {Charlotte E} and Cook, {Gary J R} and Angela Cox and Curtin, {Nicola J} and Dekker, {Lodewijk V} and Silva, {Isabel dos Santos} and Duffy, {Stephen W} and Easton, {Douglas F} and Eccles, {Diana M} and Edwards, {Dylan R} and Joanne Edwards and D Evans and Fenlon, {Deborah F} and Flanagan, {James M} and Claire Foster and Gallagher, {William M} and Montserrat Garcia-Closas and Gee, {Julia M W} and Gescher, {Andy J} and Vicky Goh and Groves, {Ashley M} and Harvey, {Amanda J} and Michelle Harvie and Hennessy, {Bryan T} and Stephen Hiscox and Ingunn Holen and Howell, {Sacha J} and Anthony Howell and Gill Hubbard and Nick Hulbert-Williams and Hunter, {Myra S} and Bharat Jasani and Jones, {Louise J} and Key, {Timothy J} and Kirwan, {Cliona C} and Anthony Kong and Kunkler, {Ian H} and Langdon, {Simon P} and Leach, {Martin O} and Mann, {David J} and Marshall, {John F} and Lesley Martin and Martin, {Stewart G} and Macdougall, {Jennifer E} and Miles, {David W} and Miller, {William R} and Morris, {Joanna R} and Moss, {Sue M} and Paul Mullan and Rachel Natrajan and O'Connor, {James P B} and Rosemary O'Connor and Carlo Palmieri and Pharoah, {Paul D P} and Rakha, {Emad A} and Elizabeth Reed and Robinson, {Simon P} and Erik Sahai and Saxton, {John M} and Peter Schmid and Smalley, {Matthew J} and Valerie Speirs and Robert Stein and John Stingl and Streuli, {Charles H} and Tutt, {Andrew N J} and Galina Velikova and Walker, {Rosemary A} and Watson, {Christine J} and Williams, {Kaye J} and Young, {Leonie S} and Thompson, {Alastair M}",
note = "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.",
year = "2013",
month = "10",
day = "1",
doi = "10.1186/bcr3493",
language = "English",
volume = "15",
journal = "Breast Cancer Research",
issn = "1465-5411",
publisher = "BioMed Central",
number = "5",

}

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 - Silva, Isabel dos Santos

AU - Duffy, Stephen W

AU - Easton, Douglas F

AU - Eccles, Diana M

AU - Edwards, Dylan R

AU - Edwards, Joanne

AU - Evans, D

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

AU - Kong, Anthony

AU - Kunkler, Ian H

AU - Langdon, Simon P

AU - Leach, Martin O

AU - Mann, David J

AU - Marshall, John F

AU - Martin, Lesley

AU - Martin, Stewart G

AU - Macdougall, Jennifer E

AU - Miles, David W

AU - Miller, William R

AU - Morris, Joanna R

AU - Moss, Sue M

AU - Mullan, Paul

AU - Natrajan, Rachel

AU - O'Connor, James P B

AU - O'Connor, Rosemary

AU - Palmieri, Carlo

AU - Pharoah, Paul D P

AU - Rakha, Emad A

AU - Reed, Elizabeth

AU - Robinson, Simon P

AU - Sahai, Erik

AU - Saxton, John M

AU - Schmid, Peter

AU - Smalley, Matthew J

AU - Speirs, Valerie

AU - Stein, Robert

AU - Stingl, John

AU - Streuli, Charles H

AU - Tutt, Andrew N J

AU - Velikova, Galina

AU - Walker, Rosemary A

AU - Watson, Christine J

AU - Williams, Kaye J

AU - Young, Leonie S

AU - Thompson, Alastair M

N1 - 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.

U2 - 10.1186/bcr3493

DO - 10.1186/bcr3493

M3 - Review article

C2 - 24286369

VL - 15

JO - Breast Cancer Research

JF - Breast Cancer Research

SN - 1465-5411

IS - 5

M1 - R92

ER -