Douglas F. Easton

Priorities for breast cancer risk assessment in UK women under age 50: a survey and discrete choice experiment

Reveals preferences for risk assessment in women under 50, suggesting a shift in practice is needed.

P022 Can breaking up sitting during dayshifts and nightshifts improve sleep?

This study explores how breaking up sitting with physical activity affects sleep architecture in shiftworkers during day and night shifts.

Breast Cancer Polygenic Risk Score Associated with Outcomes after In Situ Breast Disease

Cohort analysis links breast cancer polygenic risk score to contralateral and ipsilateral disease, suggesting personalized treatment strategies.

Incorporating Continuous Mammographic Density Into the BOADICEA Breast Cancer Risk Prediction Model

This analysis incorporates continuous mammographic density into BOADICEA, improving breast cancer risk estimates for women, suggesting better stratification.

Genetic and Cellular Architecture of Breast Cancer Risk in Multi-Ancestry Studies of 159,297 Cases and 212,102 Controls

Genome-wide association study reveals genetic correlations and common variants in breast cancer, indicating shared ancestry effects.

Supplemental Figure 2 from Breast Density Changes after Risk-Reducing Salpingo-oophorectomy in Women with a Pathogenic Germline Variant in BRCA1 or BRCA2

Cross-tabulation reveals changes in breast density in women with BRCA1 or BRCA2 variants, highlighting mammogram implications.

Supplemental Figure 1 from Breast Density Changes after Risk-Reducing Salpingo-oophorectomy in Women with a Pathogenic Germline Variant in BRCA1 or BRCA2

Cross-tabulation shows changes in breast density classifications pre and post surgery in women with BRCA mutations, suggesting significant implications for monitoring.

Supplemental Table 4 from Breast Density Changes after Risk-Reducing Salpingo-oophorectomy in Women with a Pathogenic Germline Variant in BRCA1 or BRCA2

Supplemental data reveals changes in mammographic density after risk-reducing salpingo-oophorectomy in women with BRCA1 or BRCA2 mutations, suggesting significant implications for monitoring.

Supplemental Table 3 from Breast Density Changes after Risk-Reducing Salpingo-oophorectomy in Women with a Pathogenic Germline Variant in BRCA1 or BRCA2

Supplementary data reveals changes in breast density post-surgery in women with BRCA2 mutations, highlighting risk factors.

Data from Breast Density Changes after Risk-Reducing Salpingo-oophorectomy in Women with a Pathogenic Germline Variant in BRCA1 or BRCA2

Analysis shows mammographic density declines in women with BRCA1/2 variants undergoing risk-reducing salpingo-oophorectomy, suggesting implications for breast cancer strategies.

Supplemental Table 2 from Breast Density Changes after Risk-Reducing Salpingo-oophorectomy in Women with a Pathogenic Germline Variant in BRCA1 or BRCA2

Supplemental Table 7 from Breast Density Changes after Risk-Reducing Salpingo-oophorectomy in Women with a Pathogenic Germline Variant in BRCA1 or BRCA2

Analysis shows differences in breast density changes after risk-reducing salpingo-oophorectomy in women with BRCA1 variants, indicating potential impacts on breast cancer risk.

Supplemental Table 8 from Breast Density Changes after Risk-Reducing Salpingo-oophorectomy in Women with a Pathogenic Germline Variant in BRCA1 or BRCA2

Analysis shows changes in breast density in women with BRCA2 variants undergoing salpingo-oophorectomy, indicating implications for mammogram monitoring.

Supplemental Table 5 from Breast Density Changes after Risk-Reducing Salpingo-oophorectomy in Women with a Pathogenic Germline Variant in BRCA1 or BRCA2

Observational data reveals breast density alterations in women with BRCA1 or BRCA2 mutations undergoing surgery, suggesting implications for monitoring risk.

Supplemental Table 6 from Breast Density Changes after Risk-Reducing Salpingo-oophorectomy in Women with a Pathogenic Germline Variant in BRCA1 or BRCA2

Sensitivity analysis reveals mammographic density changes in women post-salpingo-oophorectomy, indicating potential risks.

Supplemental Table 1 from Breast Density Changes after Risk-Reducing Salpingo-oophorectomy in Women with a Pathogenic Germline Variant in BRCA1 or BRCA2

Supplemental table reports breast density changes post-surgery in women with brca1 or brca2 variants, highlighting important health implications.

Adapting the BOADICEA breast and ovarian cancer risk models for the ethnically diverse UK population

BACKGROUND: BOADICEA is a widely used algorithm for predicting breast and ovarian cancer risks, using a combination of genetic and lifestyle, hormonal and reproductive risk factors. However, it has largely been developed using data from White/European individuals, limiting its applicability to other ethnicities. Here, we updated BOADICEA to provide ethnicity-specific risk estimates. METHODS: We utilised data from multiple sources to derive estimates for the distributions and effect sizes of risk factors in major UK ethnic groups (White, Black, South Asian, East Asian, and Mixed), along with ethnicity-specific population cancer incidences. We also developed a method for deriving adjusted polygenic scores for individuals of mixed genetic ancestry. RESULTS: The predicted average absolute risks were smaller in all non-White ethnic groups than in Whites, and the risk distributions were narrower. The proportion of women classified as at moderate or high risk of breast or ovarian cancer, according to national guidelines, was considerably smaller in non-Whites. DISCUSSION: The updated BOADICEA, available in the CanRisk tool ( www.canrisk.org ), is based on more appropriate estimates for non-White women in the UK. Further validation of the model in prospective studies is required. Considering these findings, risk classification guidelines for non-White women may need to be revised.

Breast Density Changes after Risk-Reducing Salpingo-oophorectomy in Women with a Pathogenic Germline Variant in BRCA1 or BRCA2

BACKGROUND: We studied changes in mammographic density (MD) among premenopausal women with a pathogenic germline variant (PGV) in the BRCA1 or BRCA2 gene, comparing those who did and did not undergo risk-reducing salpingo-oophorectomy (RRSO) in the interval between mammograms, accounting for changes in exogenous oral contraceptive or hormone replacement therapy (HRT) use. METHODS: From five studies of the International BRCA1/2 Carrier Cohort Study consortium, we included 691 participants who had two or more screening mammograms available, were less than 47 years at the time of RRSO (N = 208), or premenopausal at all mammograms without RRSO (N = 483). MD metrics [percent density (PD), dense area (DA), and non-DA] were quantified using STRATUS. Multivariable linear mixed models assessed changes in MD metrics between groups, adjusting for confounders. RESULTS: The mean PD at first mammogram was 26.8% ± 15.3 (RRSO) and 31.3% ± 18.1 (no RRSO). In a median 1.1 years between mammograms, PD decreased on average by 0.9% [95% confidence interval (CI), -1.6 to -0.2] among women who did not undergo RRSO in the interval between mammograms compared with 5.9% (95% CI, -7.4 to -4.5) among women who underwent RRSO in the interval (adjusted difference, -5.9%; 95% CI, -9.5 to -2.2; P = 0.002). Results were driven primarily by MD changes among BRCA2 PGV carriers. The use of HRT after RRSO attenuated the decline in PD. CONCLUSIONS: On average, PD and DA decrease following RRSO in premenopausal carriers, particularly among BRCA2 PGV carriers. HRT formulation affects MD changes. IMPACT: A decrease in MD may inform the potential protective effect of RRSO against breast cancer.

Primary care providers’ experience and satisfaction with personalised breast cancer screening risk communication: a descriptive cross-sectional study

Objective To describe primary care providers’ (PCPs) experience and satisfaction with receiving risk communication documents on their patient’s breast cancer (BC) risk assessment and proposed screening action plan. Design Descriptive cross-sectional study. Setting A survey was distributed to all 763 PCPs linked to 1642 women participating in the Personalized Risk Assessment for Prevention and Early Detection of Breast Cancer: Integration and Implementation (PERSPECTIVE I&I) research project in Quebec, approximately 1–4 months after the delivery of the risk communication documents. The recruitment phase took place from July 2021 to July 2022. Participants PCPs. Main outcome measures Descriptive analyses were conducted to report participants’ experiences and satisfaction with receiving risk communication. Responses to two open-ended questions were subjected to content analysis. Results A total of 168 PCPs answered the survey, from which 73% reported being women and 74% having more than 15 years of practice. Only 38% were familiar with the risk-based BC screening approach prior to receiving their patient risk category. A majority (86%) agreed with the screening approach and would recommend it to their patients if implemented at the population level. A majority of PCPs also reported understanding the information provided (92%) and expressed agreement with the proposed BC screening action plan (89%). Some PCPs recommended simplifying the materials, acknowledging the potential increase in workload and emphasising the need for careful planning of professional training efforts. Conclusion PCPs expressed positive attitudes towards a risk-based BC screening approach and were generally satisfied with the information provided. This study suggests that, if introduced in Canada in a manner similar to the PERSPECTIVE I&I project, risk-based BC screening would likely be supported by most PCPs. However, they emphasised the importance of addressing concerns such as professional training and the potential impact on workload if the approach were to be implemented at the population level. Future qualitative studies are needed to further explore the training needs of PCPs and to develop strategies for integrating this approach with the high workloads faced by PCPs.

The contribution of coding variants to the heritability of multiple cancer types using UK Biobank whole-exome sequencing data

Genome-wide association studies have been highly successful at identifying common variants associated with cancer; however, they do not explain all the inherited risks of cancer. Family-based studies, targeted sequencing, and, more recently, exome-wide association studies have identified rare coding variants in some genes associated with cancer risk, but the overall contribution of these variants to the heritability of cancer is less clear. Here, we describe a method to estimate the genome-wide contribution of rare coding variants to heritability that fits models to the burden effect sizes using an empirical Bayesian approach. We apply this method to the burden of protein-truncating variants in over 15,000 genes for 11 cancers in the UK Biobank using whole-exome sequencing data on over 400,000 individuals. We extend the method to consider the overlap of genes contributing to pairs of cancers. We found ovarian cancer to have the greatest proportion of heritability attributable to protein-truncating variants in genes (46%). The joint cancer models highlight significant clustering of cancer types, including a near-complete overlap in susceptibility genes for breast, ovarian, prostate, and pancreatic cancer. Our results provide insights into the contribution of rare coding variants to the heritability of cancer and identify additional genes with strong evidence of susceptibility to multiple cancer types.