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

ABSTRACT: 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.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.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.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.

SUBMITTER: Eccles SA

PROVIDER: S-EPMC3907091 | biostudies-other | 2013 Oct

REPOSITORIES: biostudies-other

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

Eccles Suzanne A SA Aboagye Eric O EO Ali Simak S Anderson Annie S AS Armes Jo J Berditchevski Fedor F Blaydes Jeremy P JP Brennan Keith K Brown Nicola J NJ Bryant Helen E HE Bundred Nigel J NJ Burchell Joy M JM Campbell Anna M AM Carroll Jason S JS Clarke Robert B RB Coles Charlotte E CE Cook Gary J R GJ Cox Angela A Curtin Nicola J NJ Dekker Lodewijk V LV Silva Isabel dos Santos Idos S Duffy Stephen W SW Easton Douglas F DF Eccles Diana M DM Edwards Dylan R DR Edwards Joanne J Evans D D Fenlon Deborah F DF Flanagan James M JM Foster Claire C Gallagher William M WM Garcia-Closas Montserrat M Gee Julia M W JM Gescher Andy J AJ Goh Vicky V Groves Ashley M AM Harvey Amanda J AJ Harvie Michelle M Hennessy Bryan T BT Hiscox Stephen S Holen Ingunn I Howell Sacha J SJ Howell Anthony A Hubbard Gill G Hulbert-Williams Nick N Hunter Myra S MS Jasani Bharat B Jones Louise J LJ Key Timothy J TJ Kirwan Cliona C CC Kong Anthony A Kunkler Ian H IH Langdon Simon P SP Leach Martin O MO Mann David J DJ Marshall John F JF Martin Lesley L Martin Stewart G SG Macdougall Jennifer E JE Miles David W DW Miller William R WR Morris Joanna R JR Moss Sue M SM Mullan Paul P Natrajan Rachel R O'Connor James P B JP O'Connor Rosemary R Palmieri Carlo C Pharoah Paul D P PD Rakha Emad A EA Reed Elizabeth E Robinson Simon P SP Sahai Erik E Saxton John M JM Schmid Peter P Smalley Matthew J MJ Speirs Valerie V Stein Robert R Stingl John J Streuli Charles H CH Tutt Andrew N J AN Velikova Galina G Walker Rosemary A RA Watson Christine J CJ Williams Kaye J KJ Young Leonie S LS Thompson Alastair M AM

Breast cancer research : BCR 20131001 5

<h4>Introduction</h4>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.<h4>Methods</h4>More than 100 internationally recognised specialist breast cancer scientists, clinicians and healthcare professionals collaborated to address nine thematic areas: genetics, epigenetics and epidemio ...[more]

PMID: 24286369

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Project description:OBJECTIVE:Colorectal cancer (CRC) leads to significant morbidity/mortality worldwide. Defining critical research gaps (RG), their prioritisation and resolution, could improve patient outcomes. DESIGN:RG analysis was conducted by a multidisciplinary panel of patients, clinicians and researchers (n=71). Eight working groups (WG) were constituted: discovery science; risk; prevention; early diagnosis and screening; pathology; curative treatment; stage IV disease; and living with and beyond CRC. A series of discussions led to development of draft papers by each WG, which were evaluated by a 20-strong patient panel. A final list of RGs and research recommendations (RR) was endorsed by all participants. RESULTS:Fifteen critical RGs are summarised below: RG1: Lack of realistic models that recapitulate tumour/tumour micro/macroenvironment; RG2: Insufficient evidence on precise contributions of genetic/environmental/lifestyle factors to CRC risk; RG3: Pressing need for prevention trials; RG4: Lack of integration of different prevention approaches; RG5: Lack of optimal strategies for CRC screening; RG6: Lack of effective triage systems for invasive investigations; RG7: Imprecise pathological assessment of CRC; RG8: Lack of qualified personnel in genomics, data sciences and digital pathology; RG9: Inadequate assessment/communication of risk, benefit and uncertainty of treatment choices; RG10: Need for novel technologies/interventions to improve curative outcomes; RG11: Lack of approaches that recognise molecular interplay between metastasising tumours and their microenvironment; RG12: Lack of reliable biomarkers to guide stage IV treatment; RG13: Need to increase understanding of health related quality of life (HRQOL) and promote residual symptom resolution; RG14: Lack of coordination of CRC research/funding; RG15: Lack of effective communication between relevant stakeholders. CONCLUSION:Prioritising research activity and funding could have a significant impact on reducing CRC disease burden over the next 5 years.

Project description:Prioritizing comparative effectiveness research may contribute to obtaining answers that clinicians perceive they need and may minimize research that could be considered wasteful. Our objective was to identify evidence gaps and set priorities for new systematic reviews and randomized controlled trials for managing diabetic retinopathy (DR), including diabetic macular edema (DME).Cross-sectional study.Diabetic Retinopathy Clinical Research Network (DRCR.net) investigators.We provided recommendations from the American Academy of Ophthalmology's 2012 Preferred Practice Patterns for Diabetic Retinopathy as 91 answerable clinical research questions about intervention effectiveness to 410 DRCR.net investigators to rate each question's importance from 0 (not important) to 10 (very important) using a 2-round Delphi survey and to suggest additional questions. We considered questions as high priority if at least 75% of respondents to both rounds assigned an importance rating of 5 or more in round 2. We also extracted outcome measures relevant to DR and asked respondents to identify those that must be measured in all studies. We mapped Cochrane reviews published up to March 2016 to high-priority clinical research questions.Ranking of importance of each clinical question.Thirty-two individuals completed rounds 1 and 2 and suggested 15 questions. Among the final list of 106 clinical research questions, 22 questions met our definition of high priority: 9 of 22 concerned the effectiveness of anti-VEGF therapy, and 13 of 22 focused on how often patients should be followed up (re-examination) and treatment effectiveness in patients with specific characteristics (e.g., DME). Outcomes that 75% or more of respondents marked as "must be measured in all studies" included visual acuity and visual loss, death of participants, and intraocular pressure. Only 1 prioritized question was associated with conclusive evidence from a Cochrane systematic review.A limited response rate among DRCR.net members identified 22 comparative effectiveness research questions as high priority for the management of DR, including DME, but few were associated with Cochrane reviews. These results support the need of systematic reviews and randomized controlled trials to address evidence gaps.

Project description:BackgroundThe role of the human microbiome in health and disease is an emerging and important area of research; however, there is a concern that African populations are under-represented in human microbiome studies. We, therefore, conducted a systematic survey of African human microbiome studies to provide an overview and identify research gaps. Our secondary objectives were: (i) to determine the number of peer-reviewed publications; (ii) to identify the extent to which the researches focused on diseases identified by the World Health Organization [WHO] State of Health in the African Region Report as being the leading causes of morbidity and mortality in 2018; (iii) to describe the extent and pattern of collaborations between researchers in Africa and the rest of the world; and (iv) to identify leadership and funders of the studies.MethodologyWe systematically searched Medline via PubMed, Scopus, CINAHL, Academic Search Premier, Africa-Wide Information through EBSCOhost, and Web of Science from inception through to 1st April 2020. We included studies that characterized samples from African populations using next-generation sequencing approaches. Two reviewers independently conducted the literature search, title and abstract, and full-text screening, as well as data extraction.ResultsWe included 168 studies out of 5515 records retrieved. Most studies were published in PLoS One (13%; 22/168), and samples were collected from 33 of the 54 African countries. The country where most studies were conducted was South Africa (27/168), followed by Kenya (23/168) and Uganda (18/168). 26.8% (45/168) focused on diseases of significant public health concern in Africa. Collaboration between scientists from the United States of America and Africa was most common (96/168). The first and/or last authors of 79.8% of studies were not affiliated with institutions in Africa. Major funders were the United States of America National Institutes of Health (45.2%; 76/168), Bill and Melinda Gates Foundation (17.8%; 30/168), and the European Union (11.9%; 20/168).ConclusionsThere are significant gaps in microbiome research in Africa, especially those focusing on diseases of public health importance. There is a need for local leadership, capacity building, intra-continental collaboration, and national government investment in microbiome research within Africa. Video Abstract.

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

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

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