Predicting Risk Of Cancer At Screening Research Articles

Obesity at age 20 and weight gain during adulthood increase risk of total and premature all-cause mortality: findings from women attending breast screening in Manchester

BackgroundObesity in early adulthood is associated with lower breast cancer rates in later life. This could be interpreted as a positive reinforcement of excess weight amongst younger women however, the wider implications of higher weights are less well known. This study examined the association between both obesity in early adulthood and body mass index (BMI) change through adulthood, and all-cause mortality.MethodsThe Predicting Risk of Cancer At Screening (PROCAS) study recruited 57,902 women aged 46–73 years (median age 57.2, IQR 51.8–63.7 years) from the Greater Manchester National Health Service breast screening programme in North West England between 2009 and 2015. It was used to assess associations between BMI at 20 years and cohort entry with all-cause mortality ascertained via deaths recorded on the National Breast Screening System to June 2020. Hazard ratios were estimated using proportional hazards (Cox) regression adjusted for factors at entry to the cohort: age, deprivation, bilateral oophorectomy, hormone-replacement therapy, menopausal status, ethnicity, alcohol intake, physical activity, and BMI.ResultsThe prevalence of overweight (25–30 kg/m2) and obesity (> 30 kg/m2) were 10.4% and 2.5% respectively at 20 years, increasing to 35.2% and 25.9% respectively at cohort entry. After a mean 8.7 years follow-up we observed that overweight (HR = 1.27, 95%CI = 1.10–1.47) and obesity (HR = 2.11, 95%CI = 1.67–2.66) at 20 years had a higher mortality rate compared with healthy weight. Women who were underweight/healthy weight at 20 years and gained weight to obesity at entry had a slightly increased mortality rate compared with women who were underweight/healthy weight at both time points (HR 1.16, 95%CI = 1.02–1.32). Women with overweight (HR = 1.36, 95%CI = 1.06–1.75) or obesity (HR = 1.90, 95%CI = 1.45–2.48) at both 20 years and entry had a higher mortality rate than women who were underweight/healthy weight at both points.ConclusionsWomen who self-reported overweight and obesity at 20 years had a shorter life expectancy in this cohort of women attending breast cancer screening. Weight gain from 20 years was common in this group. Girls and women should be supported to maintain a healthy weight throughout the lifespan to help increase life expectancy.Trial registration number NCT04359420, retrospectively registered 24/04/2020.

Women\u2019s health behaviour change after receiving breast cancer risk estimates with tailored screening and prevention recommendations

BackgroundThe Predicting Risk of Cancer at Screening (PROCAS) study provided women who were eligible for breast cancer screening in Greater Manchester (United Kingdom) with their 10-year risk of breast cancer, i.e., low (≤1.5%), average (1.5–4.99%), moderate (5.-7.99%) or high (≥8%). The aim of this study is to explore which factors were associated with women’s uptake of screening and prevention recommendations. Additionally, we evaluated women’s organisational preferences regarding tailored screening.MethodsA total of 325 women with a self-reported low (n = 60), average (n = 125), moderate (n = 80), or high (n = 60) risk completed a two-part web-based survey. The first part contained questions about personal characteristics. For the second part women were asked about uptake of early detection and preventive behaviours after breast cancer risk communication. Additional questions were posed to explore preferences regarding the organisation of risk-stratified screening and prevention. We performed exploratory univariable and multivariable regression analyses to assess which factors were associated with uptake of primary and secondary breast cancer preventive behaviours, stratified by breast cancer risk. Organisational preferences are presented using descriptive statistics.ResultsSelf-reported breast cancer risk predicted uptake of (a) supplemental screening and breast self-examination, (b) risk-reducing medication and (c) preventive lifestyle behaviours. Further predictors were (a) having a first degree relative with breast cancer, (b) higher age, and (c) higher body mass index (BMI). Women’s organisational preferences for tailored screening emphasised a desire for more intensive screening for women at increased risk by further shortening the screening interval and moving the starting age forward.ConclusionsBreast cancer risk communication predicts the uptake of key tailored primary and secondary preventive behaviours. Effective communication of breast cancer risk information is essential to optimise the population-wide impact of tailored screening.

The importance of ethnicity: Are breast cancer polygenic risk scores ready for women who are not of White European origin?

Polygenic risk scores (PRS) for disease risk stratification show great promise for application in general populations, but most are based on data from individuals of White European origin. We assessed two well validated PRS (SNP18, SNP143) in the Predicting‐Risk‐of‐Cancer‐At‐Screening (PROCAS) study in North‐West England for breast cancer prediction based on ethnicity. Overall, 9475 women without breast cancer at study entry, including 645 who subsequently developed invasive breast cancer or ductal carcinoma in situ provided DNA. All were genotyped for SNP18 and a subset of 1868 controls were genotyped for SNP143. For White Europeans both PRS discriminated well between individuals with and without cancer. For n = 395 Black (n = 112), Asian (n = 119), mixed (n = 44) or Jewish (n = 120) women without cancer both PRS overestimated breast cancer risk, being most marked for women of Black and Jewish origin (P < .001). SNP143 resulted in a potential mean 40% breast cancer risk overestimation in the combined group of non‐White/non‐European origin. SNP‐PRS that has been normalized based on White European ethnicity for breast cancer should not be used to predict risk in women of other ethnicities. There is an urgent need to develop PRS specific for other ethnicities, in order to widen access of this technology.

Is Breast Cancer Risk Associated with Menopausal Hormone Therapy Modified by Current or Early Adulthood BMI or Age of First Pregnancy?

Simple SummaryMenopausal hormone therapy (MHT) increases risk of developing breast cancer (BC), and women are often advised to avoid its use for this reason. In this analysis we examined the size of this effect using data from a large cohort of women attending breast cancer screening in Manchester, UK. We additionally explored the extent to which risk from MHT might be modified by current BMI, early adulthood body mass index (BMI) (age 20 years), and age of first pregnancy. Identifying modifying effects would help enable better estimation of risk associated with MHT for an individual woman. Results indicated that women using combined oestrogen and progestagen MHT were at greater risk than those receiving oestrogen-only MHT. The Relative risk associated with MHT was less for obese women than non-obese women. After adjustment for current BMI, the effect of MHT did not appear to be substantially modified by early BMI or age of pregnancy.Menopausal hormone therapy (MHT) has an attenuated effect on breast cancer (BC) risk amongst heavier women, but there are few data on a potential interaction with early adulthood body mass index (at age 20 years) and age of first pregnancy. We studied 56,489 women recruited to the PROCAS (Predicting Risk of Cancer at Screening) study in Manchester UK, 2009-15. Cox regression models estimated the effect of reported MHT use at entry on breast cancer (BC) risk, and potential interactions with a. self-reported current body mass index (BMI), b. BMI aged 20 and c. First pregnancy >30 years or nulliparity compared with first pregnancy <30 years. Analysis was adjusted for age, height, family history, age of menarche and menopause, menopausal status, oophorectomy, ethnicity, self-reported exercise and alcohol. With median follow up of 8 years, 1663 breast cancers occurred. BC risk was elevated amongst current users of combined MHT compared to never users (Hazard ratioHR 1.64, 95% CI 1.32–2.03), risk was higher than for oestrogen only users (HR 1.03, 95% CI 0.79–1.34). Risk of current MHT was attenuated by current BMI (interaction HR 0.80, 95% CI 0.65–0.99) per 5 unit increase in BMI. There was little evidence of an interaction between MHT use, breast cancer risk and early and current BMI or with age of first pregnancy.

Young adulthood body mass index, adult weight gain and breast cancer risk: the PROCAS Study (United Kingdom)

BackgroundWe tested the hypothesis that body mass index (BMI) aged 20 years modifies the association of adult weight gain and breast cancer risk.MethodsWe recruited women (aged 47–73 years) into the PROCAS (Predicting Risk Of Cancer At Screening; Manchester, UK: 2009–2013) Study. In 47,042 women, we determined BMI at baseline and (by recall) at age 20 years, and derived weight changes. We estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for new breast cancer using Cox models and explored relationships between BMI aged 20 years, subsequent weight changes and breast cancer risk.ResultsWith median follow-up of 5.6 years, 1142 breast cancers (post-menopausal at entry: 829) occurred. Among post-menopausal women at entry, BMI aged 20 years was inversely associated [HR per SD: 0.87 (95% CI: 0.79–0.95)], while absolute weight gain was associated with breast cancer [HR per SD:1.23 (95% CI: 1.14–1.32)]. For post-menopausal women who had a recall BMI aged 20 years <23.4 kg/m2 (75th percentile), absolute weight gain was associated with breast cancer [HR per SD: 1.31 (95% CIs: 1.21–1.42)], but there were no associations for women with a recall BMI aged 20 years of >23.4 kg/m2 (Pinteraction values <0.05).ConclusionsAdult weight gain increased post-menopausal breast cancer risk only among women who were <23.4 kg/m2 aged 20 years.

Breast cancer pathology and stage are better predicted by risk stratification models that include mammographic density and common genetic variants

PurposeTo improve breast cancer risk stratification to enable more targeted early detection/prevention strategies that will better balance risks and benefits of population screening programmes.Methods9362 of 57,902 women in the Predicting-Risk-Of-Cancer-At-Screening (PROCAS) study who were unaffected by breast cancer at study entry and provided DNA for a polygenic risk score (PRS). The PRS was analysed alongside mammographic density (density-residual-DR) and standard risk factors (Tyrer-Cuzick-model) to assess future risk of breast cancer based on tumour stage receptor expression and pathology.Results195 prospective incident breast cancers had a prediction based on TC/DR/PRS which was informative for subsequent breast cancer overall [IQ-OR 2.25 (95% CI 1.89–2.68)] with excellent calibration-(0.99). The model performed particularly well in predicting higher stage stage 2+ IQ-OR 2.69 (95% CI 2.02–3.60) and ER + BCs (IQ-OR 2.36 (95% CI 1.93–2.89)). DR was most predictive for HER2+ and stage 2+ cancers but did not discriminate as well between poor and extremely good prognosis BC as either Tyrer-Cuzick or PRS. In contrast, PRS gave the highest OR for incident stage 2+ cancers, [IQR-OR 1.79 (95% CI 1.30–2.46)].ConclusionsA combined approach using Tyrer-Cuzick/DR/PRS provides accurate risk stratification, particularly for poor prognosis cancers. This provides support for reducing the screening interval in high-risk women and increasing the screening interval in low-risk women defined by this model.

Psychological impact of providing women with personalised 10-year breast cancer risk estimates

BackgroundThe Predicting Risk of Cancer at Screening (PROCAS) study estimated 10-year breast cancer risk for 53,596 women attending NHS Breast Screening Programme. The present study, nested within the PROCAS study, aimed to assess the psychological impact of receiving breast cancer risk estimates, based on: (a) the Tyrer–Cuzick (T-C) algorithm including breast density or (b) T-C including breast density plus single-nucleotide polymorphisms (SNPs), versus (c) comparison women awaiting results.MethodsA sample of 2138 women from the PROCAS study was stratified by testing groups: T-C only, T-C(+SNPs) and comparison women; and by 10-year risk estimates received: 'moderate' (5–7.99%), 'average' (2–4.99%) or 'below average' (<1.99%) risk. Postal questionnaires were returned by 765 (36%) women.ResultsOverall state anxiety and cancer worry were low, and similar for women in T-C only and T-C(+SNPs) groups. Women in both T-C only and T-C(+SNPs) groups showed lower-state anxiety but slightly higher cancer worry than comparison women awaiting results. Risk information had no consistent effects on intentions to change behaviour. Most women were satisfied with information provided. There was considerable variation in understanding.ConclusionsNo major harms of providing women with 10-year breast cancer risk estimates were detected. Research to establish the feasibility of risk-stratified breast screening is warranted.

The impact of using weight estimated from mammographic images vs self-reported weight on breast cancer risk calculation.

Personalised breast screening requires assessment of individual risk of breast cancer, of which one contributory factor is weight. Self-reported weight has been used for this purpose, but may be unreliable. We explore the use of volume of fat in the breast, measured from digital mammograms. Volumetric breast density measurements were used to determine the volume of fat in the breasts of 40,431 women taking part in the Predicting Risk Of Cancer At Screening (PROCAS) study. Tyrer-Cuzick risk using self-reported weight was calculated for each woman. Weight was also estimated from the relationship between self-reported weight and breast fat volume in the cohort, and used to re-calculate Tyrer-Cuzick risk. Women were assigned to risk categories according to 10 year risk (below average <2%, average 2-3.49%, above average 3.5-4.99%, moderate 5-7.99%, high ≥8%) and the original and re-calculated Tyrer-Cuzick risks were compared. Of the 716 women diagnosed with breast cancer during the study, 15 (2.1%) moved into a lower risk category, and 37 (5.2%) moved into a higher category when using weight estimated from breast fat volume. Of the 39,715 women without a cancer diagnosis, 1009 (2.5%) moved into a lower risk category, and 1721 (4.3%) into a higher risk category. The majority of changes were between below average and average risk categories (38.5% of those with a cancer diagnosis, and 34.6% of those without). No individual moved more than one risk group. Automated breast fat measures may provide a suitable alternative to self-reported weight for risk assessment in personalized screening.

13 - Proffered Paper: A comparison of four methods of mammographic density measurement in the UK Predicting Risk Of Cancer At Screening (PROCAS) study – on behalf of the PROCAS Study team

13 - Proffered Paper: A comparison of four methods of mammographic density measurement in the UK Predicting Risk Of Cancer At Screening (PROCAS) study – on behalf of the PROCAS Study team

Can the breast screening appointment be used to provide risk assessment and prevention advice?

Breast cancer risk is continuing to increase across all societies with rates in countries with traditionally lower risks catching up with the higher rates in the Western world. Although cure rates from breast cancer have continued to improve such that absolute numbers of breast cancer deaths have dropped in many countries despite rising incidence, only some of this can be ascribed to screening with mammography, and debates over the true value of population-based screening continue. As such, enthusiasm for risk-stratified screening is gaining momentum. Guidelines in a number of countries already suggest more frequent screening in certain higher-risk (particularly, familial) groups, but this could be extended to assessing risks across the population. A number of studies have assessed breast cancer risk by using risk algorithms such as the Gail model, Tyrer-Cuzick, and BOADICEA (Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm), but the real questions are when and where such an assessment should take place. Emerging evidence from the PROCAS (Predicting Risk Of Cancer At Screening) study is showing not only that it is feasible to undertake risk assessment at the population screening appointment but that this assessment could allow reduction of screening in lower-risk groups in many countries to 3-yearly screening by using mammographic density-adjusted breast cancer risk.

PB.23. Breast density in previous screening mammograms of women with and without breast cancer

Increased mammographic density is a well-established risk factor for breast cancer; much of the evidence is based on semi-automated or visual assessment of analogue mammograms, although volumetric measures from digitally acquired mammograms are now being reported. It is also possible to quantify volumes of fat and gland from digitised analogue mammograms, given suitable calibration data. We have measured breast density in cancer cases and controls which had previous analogue screening mammograms in the PROCAS (Predicting Risk Of Cancer At Screening) study.

Breast density measurement for personalised screening

Breast density is both a modifiable risk factor for breast cancer and an indicator of the sensitivity of mammography. Reliable measurement in the screening population could enable personalised screening to maximise early detection of cancer. In the Predicting Risk of Cancer at Screening (PROCAS) study, we are investigating different approaches to measuring breast density, and we present comparative data from one subjective method and two automated volumetric methods.

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.

Abstract 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 8th 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.