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Individually tailored screening of breast cancer with genes, tumour phenotypes, clinical attributes, and conventional risk factors.

ABSTRACT: BACKGROUND: We demonstrated how to comprehensively translate the existing and updated scientific evidence on genomic discovery, tumour phenotype, clinical features, and conventional risk factors in association with breast cancer to facilitate individually tailored screening for breast cancer. METHODS: We proposed an individual-risk-score-based approach that translates state-of-the-art scientific evidence into the initiators and promoters affecting onset and subsequent progression of breast tumour underpinning a novel multi-variable three-state temporal natural history model. We applied such a quantitative approach to a population-based Taiwanese women periodical screening cohort. RESULTS: Risk prediction for pre-clinical detectable and clinical-detected breast cancer was made by the two risk scores to stratify the underlying population to assess the optimal age to begin screening and the inter-screening interval for each category and to ascertain which high-risk group requires an alternative image technique. The risk-score-based approach significantly reduced the interval cancer rate as a percentage of the expected rate in the absence of screening by 30% and also reduced 8.2% false positive cases compared with triennial universal screening. CONCLUSION: We developed a novel quantitative approach following the principle of translational research to provide a roadmap with state-of-the-art genomic discovery and clinical parameters to facilitate individually tailored breast cancer screening.

SUBMITTER: Wu YY

PROVIDER: S-EPMC3681026 | biostudies-literature | 2013 Jun

REPOSITORIES: biostudies-literature

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Individually tailored screening of breast cancer with genes, tumour phenotypes, clinical attributes, and conventional risk factors.

Wu Y-Y YY Yen M-F MF Yu C-P CP Chen H-H HH

British journal of cancer 20130514 11

<h4>Background</h4>We demonstrated how to comprehensively translate the existing and updated scientific evidence on genomic discovery, tumour phenotype, clinical features, and conventional risk factors in association with breast cancer to facilitate individually tailored screening for breast cancer.<h4>Methods</h4>We proposed an individual-risk-score-based approach that translates state-of-the-art scientific evidence into the initiators and promoters affecting onset and subsequent progression of ...[more]

PMID: 23674086

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Project description:PurposeThe aim of this study was to systematically establish a comprehensive tumour microenvironment (TME)-relevant prognostic gene and target miRNA network for breast cancer patients.MethodsBased on a large-scale screening of TME-relevant prognostic genes (760 genes) for breast cancer patients, the prognostic model was established. The primary TME prognostic genes were selected from the constructing database and verified in the testing database. The internal relationships between the potential TME prognostic genes and the prognosis of breast cancer patients were explored in depth. The associated miRNAs for the TME prognostic genes were generated, and the functions of each primary TME member were investigated in the breast cancer cell line.ResultsCompared with sibling controls, breast cancer patients showed 55 differentially expressed TME prognostic genes, of which 31 were considered as protective genes, while the remaining 24 genes were considered as risk genes. According to the lambda values of the LASSO Cox analysis, the 15 potential TME prognostic genes were as follows: ENPEP, CCDC102B, FEZ1, NOS2, SCG2, RPLP2, RELB, RGS3, EMP1, PDLIM4, EPHA3, PCDH9, VIM, GFI1, and IRF1. Among these, there was a remarkable linear internal relationship for CCDC102B but non-linear relationships for others with breast cancer patient prognosis. Using the siRNA technique, we silenced the expression of each TME prognostic gene. Seven of the 15 TME prognostic genes (NOS2, SCG2, RGS3, EMP1, PDLIM4, PCDH9, and GFI1) were involved in enhancing cell proliferation, destroying cell apoptosis, promoting cell invasion, or migration in breast cancer. Six of them (CCDC102B, RPLP2, RELB, EPHA3, VIM, and IRF1) were favourable for maintaining cell invasion or migration. Only two of them (ENPEP and FEZ1) were favourable for the processes of cell proliferation and apoptosis.ConclusionsThis integrated study hypothesised an innovative TME-associated genetic functional network for breast cancer patients. The external relationships between these TME prognostic genes and the disease were measured. Meanwhile, the internal molecular mechanisms were also investigated.

Project description:BackgroundInternet-delivered interventions can provide remarkable opportunities in addressing breast cancer survivors' unmet support care needs, as they present an effective strategy to improve care coordination and provide access to efficacious, cost-efficient and convenient survivorship care. Nevertheless, research focusing on improving survivors' psychosocial needs using internet-based tools is scarce and its practical implementation is limited.ObjectivesTo study the acceptability, feasibility, efficacy and cost-effectiveness of iNNOVBC, a 10 weeks guided internet-delivered individually-tailored Acceptance and Commitment Therapy (ACT)-influenced cognitive behavioural (CBT) intervention developed to improve mild to moderate anxiety and depression in Breast cancer survivors when compared to treatment as usual (TAU) in a waiting list control group (WLC).MethodsA two-arm, parallel, open label, multicentre, waiting list randomized controlled trial will be conducted to investigate the efficacy and cost-effectiveness of INNOVBC. The primary outcomes in this research will be anxiety and depression. Secondary outcomes will include psychological flexibility, fatigue, insomnia, sexual dysfunction and Health Related Quality of Life (HRQoL).Ethical approvalThis study has been reviewed and approved by Comissão Nacional de Proteção de Dados; Instituto Português de Oncologia do Porto Francisco Gentil; Unidade Local de Saúde de Matosinhos, EPE; Centro Hospitalar de São João and Ordem dos Psicólogos ethical committees.Expected resultsIt is anticipated that iNNOVBC will show to be an efficacious and cost-effective program in improving the outcomes of interest in this study, as opposed to a WLC under TAU. The results of this research will be published in accordance with CONSORT-EHEALTH guidelines.ConclusionsThis study will inform on the acceptability, feasibility, efficacy and cost-effectiveness of iNNOVBC, in improving psychosocial outcomes in breast cancer survivors when compared to TAU in a WLC. Its conclusions will contribute to understand the idiosyncrasies of designing and implementing internet-delivered interventions in breast cancer survivors.Trial Registration code: INNOVBC (NCT03275727).

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Individually tailored screening of breast cancer with genes, tumour phenotypes, clinical attributes, and conventional risk factors.

Publications

Individually tailored screening of breast cancer with genes, tumour phenotypes, clinical attributes, and conventional risk factors.

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