Personalized Risk Assessment for Prevention and Early Detection of Breast Cancer: Integration and Implementation (PERSPECTIVE I&I)

Journal of Personalized Medicine, Journal Year: 2021, Volume and Issue: 11(6), P. 511 - 511

Published: June 4, 2021

Early detection of breast cancer through screening reduces mortality. The benefits must also be considered within the context potential harms (e.g., false positives, overdiagnosis). Furthermore, while risk is highly variable population, most programs use age to determine eligibility. A risk-based approach expected improve benefit-harm ratio programs. PERSPECTIVE I&I (Personalized Risk Assessment for Prevention and Detection Breast Cancer: Integration Implementation) project seeks personalized assessment allow a cost-effective, population-based best practices implementation in Canada. This commentary describes four inter-related activities that comprise project. 1: Identification validation novel moderate high-risk susceptibility genes. 2: Improvement, validation, adaptation prediction web-tool Canadian context. 3: Development piloting socio-ethical framework support screening. 4: Economic analysis optimize Risk-based prevention benefit all women, empowering them work with their healthcare provider make informed decisions about prevention.

Language: Английский

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Artificial intelligence in mammographic phenotyping of breast cancer risk: a narrative review

Breast Cancer Research, Journal Year: 2022, Volume and Issue: 24(1)

Published: Feb. 20, 2022

Improved breast cancer risk assessment models are needed to enable personalized screening strategies that achieve better harm-to-benefit ratio based on earlier detection and outcomes than existing guidelines. Computational mammographic phenotypes have demonstrated a promising role in prediction. With the recent exponential growth of computational efficiency, artificial intelligence (AI) revolution, driven by introduction deep learning, has expanded utility imaging predictive models. Consequently, AI-based imaging-derived data led some most tools for precision screening.This review aims synthesize current state-of-the-art applications AI phenotyping risk. We discuss fundamentals explore computing advancements made image analysis essential refining assessment. Specifically, we use derived from digital mammography as well tomosynthesis. Different aspects targeted including (a) robust reproducible evaluations density, well-established factor, (b) woman's inherent risk, (c) identification women who likely be diagnosed with cancers after negative or routine screen due masking rapid aggressive tumor. Lastly, challenges unique future directions this research field.We provide useful reference researchers investigating image-based while indicating key priorities that, if properly addressed, could accelerate implementation AI-assisted stratification refine individualize strategies.

Language: Английский

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Study protocol comparing the ethical, psychological and socio-economic impact of personalised breast cancer screening to that of standard screening in the “My Personal Breast Screening” (MyPeBS) randomised clinical trial

BMC Cancer, Journal Year: 2022, Volume and Issue: 22(1)

Published: May 6, 2022

Abstract Background The MyPeBS study is an ongoing randomised controlled trial testing whether a risk-stratified breast cancer screening strategy non-inferior, or eventually superior, to standard age-based at reducing incidence of stage 2 more cancers. This large European Commission-funded initiative aims include 85,000 women aged 40 70 years, without prior and not previously identified high risk in six countries (Belgium, France, Italy, Israel, Spain, UK). A specific work package within examines psychological, socio-economic ethical aspects this new strategy. It compares women’s reported data outcomes both arms on the following issues: general anxiety, cancer-related worry, understanding information-seeking behaviour, socio-demographic economic characteristics, quality life, perception, intention change health-related behaviours, satisfaction with trial. Methods At inclusion, 3-months, 1-year 4-years, each woman participating asked fill online questionnaires. Descriptive statistics, bivariate analyses, subgroup comparisons analysis variations over time will be performed appropriate tests assess differences between arms. Multivariate regression models allow modelling different patient such as comprehension information provided, anxiety seeking behaviour. In addition, qualitative (48 semi-structured interviews conducted France UK arm), help further understand participants’ acceptability trial, their experience assessment. Discussion Beyond scientific medical objectives clinical study, it critical acknowledge consequences paradigm shift for women. Indeed, introducing risk-based relying individual biological also implies addressing non-biological (e.g. social status health literacy) from perspective, ensure equal access healthcare. results present facilitate making recommendations implementation end accompany any potential Trial registration Study sponsor: UNICANCER. My personalised (MyPeBS). Clinicaltrials.gov (2018) available at: https://clinicaltrials.gov/ct2/show/NCT03672331 Contact: Cécile VISSAC SABATIER, PhD, + 33 (0)1 73 79 77 58 ext 330,142,114,293, [email protected].

Language: Английский

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Nanoparticles Targeting Receptors on Breast Cancer for Efficient Delivery of Chemotherapeutics

Biomedicines, Journal Year: 2021, Volume and Issue: 9(2), P. 114 - 114

Published: Jan. 26, 2021

The journey of chemotherapeutic drugs from the site administration to action is confronted by several factors including low bioavailability, uneven distribution in major organs, limited accessibility drug molecules distant tumor tissues, and lower therapeutic indexes. These unavoidable features classical chemotherapeutics necessitate an additional high, repetitive dose obtain maximum responses with result unintended adverse side effects. An erratic microenvironment, notable drawbacks conventional chemotherapy, multidrug-resistant mechanisms breast cancer cells warrant precisely designed therapeutics for treatment cancers. In recent decades, nanoparticles have been deployed delivery standard anticancer maximize potency while minimizing effects increase quality span life. Several organic inorganic nanoplatforms that exploiting distinctive microenvironment offer favorable physicochemical properties pharmacokinetic profiles a parent drug, higher amounts pathological its controlled release, thereby improving balance between efficacy toxicity. Advances this front included design construction targeted conjugating homing devices like peptide, ligand, Fab on surface nanomaterials navigate nanoparticledrug complexes towards target cell minimal destruction healthy cells. Furthermore, actively targeting can facilitate cellular uptake nanoparticle-loaded constructs via binding specific receptors expressed aberrantly cell. Herein, we present overview principle approaches, drug-nanoparticle conjugates multiple moieties highlighting evaluation preclinical studies. We conclude understanding translational gap challenges would show possible future directions foster development novel nanotherapeutics.

Language: Английский

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Prospective validation of the BOADICEA multifactorial breast cancer risk prediction model in a large prospective cohort study

Journal of Medical Genetics, Journal Year: 2022, Volume and Issue: 59(12), P. 1196 - 1205

Published: Sept. 26, 2022

Background The multifactorial Breast and Ovarian Analysis of Disease Incidence Carrier Estimation Algorithm (BOADICEA) breast cancer risk prediction model has been recently extended to consider all established factors. We assessed the clinical validity in a large independent prospective cohort. Methods validated BOADICEA (V.6) Swedish KARolinska Mammography Project for Risk Prediction Cancer (KARMA) cohort including 66 415 women European ancestry (median age 54 years, IQR 45–63; 816 incident cancers) without previous diagnosis. calculated 5-year risks on basis questionnaire-based factors, pedigree-structured first-degree family history, mammographic density (BI-RADS), polygenic score (PRS) based 313-SNPs, pathogenic variant status 8 susceptibility genes: BRCA1 , BRCA2 PALB2 CHEK2 ATM RAD51C RAD51D BARD1 . Calibration was by comparing observed expected deciles predicted calibration slope. discriminatory ability using area under curve (AUC). Results Among individual components, PRS contributed most stratification. well calibrated predicting low-risk high-risk when all, or subsets factors are included prediction. Discrimination maximised considered (AUC=0.70, 95% CI: 0.66 0.73; expected-to-observed ratio=0.88, 0.75 1.04; slope=0.97, 0.95 0.99). full classified 3.6% as high (5-year ≥3%) 11.1% very low <0.33%). Conclusion provides valid predictions personalised decision-making disease prevention screening.

Language: Английский

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Enhancing the BOADICEA cancer risk prediction model to incorporate new data onRAD51C,RAD51D,BARD1updates to tumour pathology and cancer incidence

Journal of Medical Genetics, Journal Year: 2022, Volume and Issue: 59(12), P. 1206 - 1218

Published: Sept. 26, 2022

Background BOADICEA (Breast and Ovarian Analysis of Disease Incidence Carrier Estimation Algorithm) for breast cancer the epithelial tubo-ovarian (EOC) models included in CanRisk tool ( www.canrisk.org ) provide future risks based on pathogenic variants cancer-susceptibility genes, polygenic risk scores, density, questionnaire-based factors family history. Here, we extend to include effects recently established EOC susceptibility up-to-date age-specific pathology distributions continuous factors. Methods was extended further incorporate associations BARD1 , RAD51C RAD51D with risk. The model association PALB2 Age-specific oestrogen-receptor-negative triple-negative status variant carriers these genes CHEK2 ATM were also incorporated. A novel method developed, exemplified by including adult height as continuous. Results explain 0.31% variance. When incorporated into multifactorial model, 34%–44% would be reclassified near-population 15%–22% high-risk categories UK National Institute Health Care Excellence guidelines. Under 62%, 35% 3% have lifetime <5%, 5%–10% >10%, respectively. Including continuous, increased relative variance from 0.002 0.010. Conclusions These extensions will allow better personalised more informed choices screening, prevention, factor modification or other risk-reducing options.

Language: Английский

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Acceptability of risk stratification within population-based cancer screening from the perspective of healthcare professionals: A mixed methods systematic review and recommendations to support implementation

PLoS ONE, Journal Year: 2023, Volume and Issue: 18(2), P. e0279201 - e0279201

Published: Feb. 24, 2023

Background Introduction of risk stratification within population-based cancer screening programmes has the potential to optimise resource allocation by targeting towards members population who will benefit from it most. Endorsement healthcare professionals is necessary facilitate successful development and implementation risk-stratified interventions. Therefore, this review aims explore whether using acceptable identify any requirements for implementation. Methods We searched four electronic databases January 2010 October 2021 quantitative, qualitative, or primary mixed methods studies reporting professional and/or other stakeholder opinions on acceptability screening. Quality included was assessed Mixed Appraisal Tool. Data were analysed Joanna Briggs Institute convergent integrated approach analysis mapped onto Consolidated Framework Implementation Research a ‘best fit’ approach. PROSPERO record CRD42021286667. Results A total 12,039 papers identified through literature search seven in review, six context breast one considering ovarian cancer. Risk broadly considered acceptable, with findings covering all five domains framework: intervention characteristics, outer setting, inner characteristics individuals, process. Across these domains, key areas that as needing further consideration support were: need greater evidence, particularly de-intensifying screening; limitations; staff training clear communication; importance public involvement. Conclusions largely professionals, but be required successfully Future research should focus strengthening evidence base stratification, relation reducing frequency among low-risk cohorts across different types.

Language: Английский

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Gender-Specific Genetic Predisposition to Breast Cancer: BRCA Genes and Beyond

Cancers, Journal Year: 2024, Volume and Issue: 16(3), P. 579 - 579

Published: Jan. 30, 2024

Among neoplastic diseases, breast cancer (BC) is one of the most influenced by gender. Despite common misconceptions associating BC as a women-only disease, can also occur in men. Additionally, transgender individuals may experience BC. Genetic risk factors play relevant role predisposition, with important implications precision prevention and treatment. The genetic architecture susceptibility similar women men, high-, moderate-, low-penetrance variants; however, some sex-specific features have emerged. Inherited high-penetrance pathogenic variants (PVs) BRCA1 BRCA2 genes are strongest factor. PVs more commonly associated increased female male BC, respectively. Notably, BRCA-associated BCs characterized pathologic features. Recently, next-generation sequencing technologies helped to provide insights on moderate-penetrance variants, particularly PALB2, CHEK2, ATM genes, while international collaborative genome-wide association studies contributed evidence their combined effect polygenic models, modulators BRCA1/2 PV carriers. Overall, all these suggested that basis although similar, differ from Evaluating component distinct entity first step improve both personalized assessment therapeutic choices patients sexes order reach gender equality care. In this review, we summarize latest research field predisposition particular focus similarities differences discuss implications, challenges, open issues surround establishment gender-oriented clinical management for

Language: Английский

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Estimation of age of onset and progression of breast cancer by absolute risk dependent on polygenic risk score and other risk factors

Cancer, Journal Year: 2024, Volume and Issue: 130(9), P. 1590 - 1599

Published: Jan. 4, 2024

Abstract Background Genetic, lifestyle, reproductive, and anthropometric factors are associated with the risk of developing breast cancer. However, it is not yet known whether polygenic score (PRS) absolute based on a combination progression This study aims to estimate distribution sojourn time (pre‐clinical screen‐detectable period) mammographic sensitivity by cancer derived from profile other factors. Methods The authors used data population‐based case‐control study. Six categories 10‐year different combinations were using Breast Ovarian Analysis Disease Incidence Carrier Estimation Algorithm. Women classified into low, medium, high‐risk groups. constructed continuous‐time multistate model. To calculate time, they simulated trajectories subjects through disease states. Results There was little difference in large overlap 95% confidence interval (CI) between groups across six PRS studied. age entry state varied category, mean 53.4 years (95% CI, 52.2–54.1) 57.0 55.1–57.7) low‐risk women, respectively. Conclusion In risk‐stratified screening, at start but necessarily frequency should be tailored woman’s level. optimal screening strategy that would improve benefit‐to‐harm balance cost‐effectiveness programs needs

Language: Английский

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Antibody-drug conjugates targeting SSEA-4 inhibits growth and migration of SSEA-4 positive breast cancer cells

Cancer Letters, Journal Year: 2025, Volume and Issue: 611, P. 217453 - 217453

Published: Jan. 10, 2025

Language: Английский

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