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

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.

Categories

Keyword(s)

Afatinib ATM protein biological marker BRCA1 protein BRCA2 protein checkpoint kinase 2 denosumab everolimus fenretinide ganetespib goserelin lapatinib lasofoxifene letrozole luminespib metformin neratinib paclitaxel pertuzumab phosphatidylinositol 3 5 trisphosphate 3 phosphatase protein kinase LKB1 protein p53 raloxifene resveratrol saracatinib tamoxifen trastuzumab uvomorulin abdominal obesity advanced cancer alcohol consumption allele angiogenesis article behavior change bioinformatics body composition body weight bone metastasis breast cancer breast development breast metastasis breast reconstruction caloric restriction cancer adjuvant therapy cancer epidemiology cancer genetics cancer hormone therapy cancer immunotherapy cancer prognosis cancer risk cancer survival cancer susceptibility cell death cell lineage cell polarity chemosensitivity circulating tumor cell clinical decision making cognitive therapy cost effectiveness analysis cytology distant metastasis DNA damage drug efficacy epigenetics epithelial mesenchymal transition exercise fat intake fine needle aspiration biopsy gene expression genetic association genetic predisposition genetic screening genetic susceptibility genetic variability genotype hormonal therapy human in vitro study in vivo study lifestyle modification longevity low drug dose lymphangiogenesis malignant transformation mastectomy medical research meta analysis (topic) micrometastasis molecularly targeted therapy monotherapy nonhuman nuclear magnetic resonance imaging patient satisfaction personalized medicine phase 3 clinical trial (topic) physical activity positron emission tomography psychological well being quality of life radiofrequency ablation radiosensitivity randomized controlled trial (topic) signal transduction single nucleotide polymorphism smoking social marketing stereotactic body radiation therapy terminal care translational research tumor microenvironment tumor xenograft.

License

CC BY-NC-ND 4.0