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Critical research gaps and translational priorities for the successful prevention and treatment of breast cancerEccles, 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.; et al. (BioMed Central, 2013-10-01)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.
New paradigms for BRCA1/BRCA2 testing in women with ovarian cancer: results of the Genetic Testing in Epithelial Ovarian Cancer (GTEOC) studyPlaskocinska, Inga; Shipman, Hannah; Drummond, James; Thompson, Edward; Buchanan, Vanessa; Newcombe, Barbara; Hodgkin, Charlotte; Barter, Elisa; Ridley, Paul; Ng, Rita; et al. (2016-05-12)Background: Over recent years genetic testing for germline mutations in BRCA1/BRCA2 has become more readily available because of technological advances and reducing costs. The Genetic Testing in Epithelial Ovarian Cancer (GTEOC) Study explored the feasibility and acceptability of offering genetic testing to all women recently diagnosed with epithelial ovarian cancer (EOC). Methods: From 1st July 2013 to 30th June 2015 women newly diagnosed with EOC were recruited through six sites in East Anglia, UK. Eligibility was irrespective of patient age and family history of cancer. The psychosocial arm of the study utilised self-report, psychometrically validated questionnaires (Depression Anxiety and Stress Scale, DASS-21; Impact of Event Scale, IES) and cost analysis was performed. Results: 232 women were recruited and 18 mutations were detected (12 in BRCA1, 6 in BRCA2) giving a mutation yield of 8% which increases to 12% in unselected women <70 years (17/146) and 1% in unselected women >70 years (1/86). IES and DASS-21 scores in response to genetic testing were significantly lower than equivalent scores in response to cancer diagnosis (p<.001). Correlation tests indicated that whilst older age is a protective factor against any traumatic impacts of genetic testing, no significant correlation exists between age and distress outcomes. Conclusion: The mutation yield in unselected women diagnosed with EOC from a heterogeneous population with no founder mutations was 8% in all ages and 12% in women under 70. Unselected genetic testing in women with EOC was acceptable to patients and is potentially less resource-intensive than current standard practice.