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Dive into the research topics where Jack Cuzick is active.

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Featured researches published by Jack Cuzick.


Journal of Clinical Oncology | 2017

Participant-Reported Symptoms and Their Effect on Long-Term Adherence in the International Breast Cancer Intervention Study I (IBIS I)

Samuel G. Smith; Ivana Sestak; Anthony Howell; John Forbes; Jack Cuzick

Purpose To assess the role of participant-reported symptoms on long-term adherence to preventive therapy in the United Kingdom sample of the International Breast Cancer Intervention Study (IBIS-I). IBIS-I was a randomized controlled trial that investigated the effectiveness of tamoxifen in reducing the risk of breast cancer among women at increased risk of the disease. Participants and Methods Women were randomly assigned to tamoxifen versus placebo (20 mg/day; n = 4,279). After 456 exclusions, 3,823 women were included in this analysis. Adherence (< 4.5 years or ≥ 4.5 years) was calculated using data from six monthly clinical visits. Analyses were adjusted for age, Tyrer-Cuzick risk, smoking, use of hormone replacement therapy, menopausal status, baseline menopausal symptoms, and treatment. Results Overall, 69.7% of women were adherent for at least 4.5 years (tamoxifen: 65.2% v placebo: 74.0%; P < .001). Differences in adherence between treatment arms were observed from 12 months onward (all P < .01) and were largest at 54 months. Dropout rates were highest in the first 12 to 18 months and decreased thereafter. Women reporting nausea/vomiting were less likely to be adherent in both the tamoxifen (odds ratio [OR], 0.57; 95% CI, 0.37 to 0.86; P = .007) and placebo (OR, 0.58; 95% CI, 0.37 to 0.93; P = .023) arms. Headaches were associated with adherence only in the placebo arm (OR, 0.62; 95% CI, 0.42 to 0.91; P = .016), whereas gynecologic symptoms were significant only in the tamoxifen arm (OR, 0.77; 95% CI, 0.62 to 0.97; P = .024). Effect sizes for each symptom on adherence were not significantly different between the treatment groups (P > .05). In both treatment arms, we observed significant trends for lower adherence with increasing severity for all symptoms (P < .01) except headaches (P = .054). Conclusion In the IBIS-I trial, experiencing predefined symptoms in the first 6 months reduced long-term adherence. Effects were similar between treatment arms, suggesting that women were attributing age-related symptoms to preventive therapy. Interventions were required to support symptom management.


Cancer Research | 2016

Abstract PD1-07: Mammographic density and SNPs add to Tyrer-Cuzick and Gail model breast cancer risk in a UK screening cohort

D G R Evans; Susan M. Astley; Adam R. Brentnall; Anthony Howell; Jack Cuzick

Background: The predicting risk of cancer at screening study (PROCAS) in Manchester UK is a prospective study of breast cancer risk estimation. This article considers whether mammographic density and SNPs in PROCAS may help refine breast cancer risk estimation using the Gail (BCRAT) and Tyrer-Cuzick (TC, or IBIS) models, based on incident and prevalent breast cancers identified between two three-yearly screening rounds. Methods: Mammographic density was measured at entry as a percentage using the average visual assessment from two trained readers. Tyrer-Cuzick and Gail risks were based on a questionnaire completed at the same time. The contribution of density to risk models was assessed after adjustment for age and body mass index (BMI) using odds ratios (ORs) and profile likelihood confidence intervals (CIs). A secondary analysis compared cancer pathology characteristics using a two-sided Wilcoxon test. Eighteen breast cancer risk variants (SNP18) were assessed with a polygenic risk score (PRS) alongside TC and density in a subset of 8870 women with 341 prospective cancers. Results: Analysis included 50628 women of routine screening age (47-73 yrs), recruited between Aug 2009 and Jul 2014. 697 had a breast cancer diagnosed after enrolment. Median follow-up was 3.2 years. Visually assessed percentage breast density (inter-quartile range odds ratio (IQR OR) 1.48 (95%CI 1.34-1.63)) was a slightly stronger univariate risk factor than TC (IQR OR 1.36 (1.25-1.48)) or Gail (IQR OR 1.22 (1.12-1.33)). It continued to add information after allowing for TC (IQR OR 1.47 (1.33-1.62)) or Gail (IQR OR 1.45 (1.32-1.60)). 36472/50628 (72%) women had less than 3.5% 10-yr risk from the TC model and breast density combined. Women with dense breasts were more likely to have a higher stage breast cancer (P Conclusion: Breast density and SNPs when combined with the TC or Gail risk model identify a larger number of high risk women at screening, and it is associated with higher stage of disease. Approximately 70% of women are identified with a combined TC and density risk assessment of less than 3.5% 10-yr risk (average or less than average risk), for whom three-yearly screening might be effective. SNP18 adds further precision and addition of further newly identified SNPs is likely to add greater discrimination. Citation Format: Evans DG, Astley SM, Brentnall A, Howell A, Cuzick J. Mammographic density and SNPs add to Tyrer-Cuzick and Gail model breast cancer risk in a UK screening cohort. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr PD1-07.


Cancer Research | 2017

Abstract S5-03: Menopausal symptoms as predictors of long-term adherence in the International breast cancer intervention study (IBIS-1)

Sg Smith; Ivana Sestak; John Forbes; Anthony Howell; Jack Cuzick

Tamoxifen reduces the risk of breast cancer among women at increased risk of the disease. The effectiveness of the drug is dependent on its appropriate use for the duration of therapy. Adherence for the full course of preventive therapy ranges from 60-80%. Early discontinuation is largely attributed to side-effects, but no studies have validated this using 5-year follow-up data. We assessed the role of menopausal side-effects on long-term adherence in the UK arm of the International Breast Cancer Intervention Study (IBIS-1). In the IBIS-1 trial, 4279 women in the UK were randomised to placebo vs. tamoxifen (20mg/day). A total of 292 were excluded (breast cancer, death, or other cancer), leaving 3987 to be included in the analysis (2000 placebo arm, 1987 tamoxifen arm). Adherence was calculated using data from six monthly clinical visits during the trial. Adherence ( Overall, 66.8% of women were adherent for at least 4.5 years (placebo: 71.5% vs. tamoxifen: 62.1%, p In the IBIS-I trial, we observed a significant effect of common menopausal symptoms on long-term adherence. These effects were largely similar between tamoxifen and placebo arms, suggesting women are attributing age-related menopausal symptoms to preventive therapy. To ensure women experience the full benefit of preventive therapy, interventions are required to support the management of menopausal symptoms and to promote adherence. The higher rate of drop-out in the early months of the trial suggests early intervention may be an effective way to promote long-term adherence. Citation Format: Smith SG, Sestak I, Forbes J, Howell A, Cuzick JJ. Menopausal symptoms as predictors of long-term adherence in the International breast cancer intervention study (IBIS-1) [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr S5-03.


Cancer Research | 2011

P4-11-07: Feasibility and Acceptability of Offering Breast Cancer Risk Estimation in the Context of the UK National Health Service Breast Cancer Screening Programme: A New Paradigm for Cancer Prevention.

Dgr Evans; Susan M. Astley; Paula Stavrinos; S Sahin; Sarah L. Ingham; Helen McBurney; B Eckersley; Mary E. Wilson; Ursula Beetles; Michelle Harvie; Ruth Warren; Jamie C. Sergeant; Alan Hufton; Jane Warwick; William G. Newman; Iain Buchan; Jack Cuzick; Anthony Howell

Background: Currently there are no real attempts internationally to tailor breast screening programmes to individual risk Methods: We have assessed the feasibility of collecting breast cancer risk information during routine mammographic screening in the National Health Service Breast Screening Programme (NHSBSP) in England, in order to consider, ultimately, adapting the screening interval to risk of breast cancer and introducing preventive strategies in women at high risk. The study Predicting Risk Of Cancer At Screening (PROCAS) aims to recruit 60,000 women over 3 years. Results: 26,000 women (June 8 th 2011) have so far given consent to join the study. Thirty six percent of the first 20,000 women in nineteen screening sites in Manchester consented to enter the study and completed a risk factor questionnaire. The median 10 year breast cancer risk was 2.65%, with 926 (9.26%) of the first 10,000 women having a 10 year risk of ≥5% and 92 (0.92%) having a 10 year risk of ≥8% (Tyrer-Cuzick), IQR:1.35. 832 (8.32%) women had a mammographic density of 60% or greater (Visual Analogue Scale). We collected saliva samples from 1019 women for genetic analysis and will extend this to 18% of participants. Of those who agreed to participate in the study, 94% indicated that they wished to know their breast cancer risk. Women with a 10-year risk of ≥8%, and women with a 10-year risk of ≥5% and mammographic density ≥60% were invited to attend or be telephoned to be counselled. To date 138 have accepted with 135, so far, having received risk counselling. Nineteen percent of the high-risk women identified subsequently decided to enter a randomised breast cancer prevention study with either a dietary or drug intervention (IBIS2, anastrazole vs placebo). Results from the first 1,000 women who provided DNA samples suggest that the risk information from the 18 validated SNPS may enhance existing risk models. Conclusion: This study demonstrates that it is feasible to determine individual breast cancer risk and offer women appropriate risk-reducing interventions within the context of a population-based mammographic screening programme. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-11-07.


Cancer Research | 2018

Abstract P3-08-01: Prognostic performance of EndoPredict in invasive lobular carcinoma

Ivana Sestak; Ralf Kronenwett; Carsten Denkert; Jack Cuzick; M. Dowsett


Cancer Research | 2018

Abstract P4-08-01: Not presented

Anthony Howell; Elaine Harkness; J Fox; Susan M. Astley; J Wiseman; M Eriksson; Mary E. Wilson; R. Warren; P Hall; Jack Cuzick; Gareth Evans


Cancer Research | 2018

Abstract P5-15-01: Participant-reported symptoms as predictors of long-term adherence of endocrine therapy in the International breast cancer intervention studies 2 (IBIS-2)

Ivana Sestak; Sg Smith; M Sleeth; Anthony Howell; Jack Cuzick


Archive | 2016

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D. Gareth Evans; Susan M. Astley; Paula Stavrinos; Elaine Harkness; Louise S Donnelly; Sarah Dawe; Ian Jacob; Michelle Harvie; Jack Cuzick; Adam R. Brentnall; Mary Wilson; Fiona Harrison; Katherine Payne; Anthony Howell


Archive | 2016

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D. Gareth Evans; Susan M. Astley; Paula Stavrinos; Elaine Harkness; Louise S Donnelly; Sarah Dawe; Ian Jacob; Michelle Harvie; Jack Cuzick; Adam R. Brentnall; Mary Wilson; Fiona Harrison; Katherine Payne; Anthony Howell


Archive | 2016

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D. Gareth Evans; Susan M. Astley; Paula Stavrinos; Elaine Harkness; Louise S Donnelly; Sarah Dawe; Ian Jacob; Michelle Harvie; Jack Cuzick; Adam R. Brentnall; Mary Wilson; Fiona Harrison; Katherine Payne; Anthony Howell

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Adam R. Brentnall

Queen Mary University of London

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Anthony Howell

Queen Mary University of London

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David Guthrie

Medical Research Council

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Elaine Harkness

University Hospital of South Manchester NHS Foundation Trust

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Paula Stavrinos

University Hospital of South Manchester NHS Foundation Trust

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Peter Simmonds

University of Southampton

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