Jennifer D. Brooks

Background/Objectives: Risk-based breast cancer (BC) screening can provide tailored recommendations based on individual risk. We aimed to identify key predictors for BC risk stratification to inform implementation in screening programs. Methods: We estimated 10-year BC risks using BOADICEA v.6 (CanRisk) in 3753 women aged 40–70 with no cancer history from the PERSPECTIVE I&I cohort. The primary endpoint was risk reclassification, assessed as the proportion of women whose assigned 10-year risk category changed when using different risk factor combinations against a full multifactorial model including questionnaire-based risk factors (QRFs), polygenic score (PGS), mammographic density (MD), and pedigree-structured first- and second-degree family history (FH) of breast, ovarian, pancreatic and prostate cancer, including both affected and unaffected relatives. Relative risk thresholds were set as <1.5 (average), 1.5–2.7 (higher-than-average), and ≥2.7 (high), equivalent to the remaining lifetime risk categories of <15%, 15–25% and ≥25% for women aged 30 (the anchor) to age 80. We quantified individual-level reclassification flows by direction and magnitude. Results: Excluding PGS from risk calculations led to the highest overall reclassification. Using only the BC status in first- and second-degree relatives produced comparable risk classification to that of the full FH data that included breast, ovarian, prostate and pancreatic cancer (reclassification = 0.5%). However, collecting only affected relatives led to overestimation of risk. Excluding either PGS, MD or FH resulted in a greater proportion of reclassification among younger women. Adding the PGS to risk factors already collected in provincial screening programs reduced reclassification from 23% to ~13%. Conclusions: PGS, MD, QRFs and FH of BC in affected and unaffected first- and second-degree relatives are key for refining risk stratification. These findings provide real-world evidence on how incorporating different sets of risk factors, both those routinely collected in screening programs and those requiring additional data collection, affect individual-level risk classification amongst a population-based cohort, and how the impacts differ across age groups. While risk classification reflects model-based changes in estimated risk categories rather than direct evidence of mis-screening or clinical outcomes, comparison with the current eligibility criteria used to identify women at higher-than-average risk highlights the potential clinical value of a multifactorial risk assessment approach in ensuring more appropriate screening strategies.

Implementing population-wide risk-stratified breast screening (RSBS) requires coordinated planning across diverse stakeholders and adaptation within complex healthcare systems. We convened a multi-stakeholder workshop with 34 policymakers, breast screening program leaders and healthcare professionals across Canada. Participants co-envisioned an RSBS program and focused on defining care pathways, the implementation roadmap, stakeholder engagement, and workforce training. A national, flexible RSBS strategy was proposed with multiple entry points and timings for risk assessment, interoperable information technology systems, phased roll-out, and an embedded learning healthcare system. The resulting actionable plans support RSBS implementation in Canada and offer transferable insights for planning RSBS in varied international settings.

Asthma is a common respiratory disease in Canada, representing a significant burden on the health of the population and the healthcare system. While studies have attributed an association between obesity and asthma, understanding of this relationship remains underexplored in the Canadian population. This study aims to describe the association between BMI and current asthma in adults living across Canada. This study used cross-sectional data from the 2017-2018 Canadian Community Health Survey of individuals aged 18 years and older who reported currently having asthma. Current asthma was defined as having been previously diagnosed with asthma and experiencing asthma symptoms or asthma attacks in the past 12 months. Prevalence ratios (PRs) and 95% confidence intervals (CIs) were estimated using log-binomial regression, modelling the association between BMI (underweight/normal weight (< 25 kg/m²), overweight (25- < 30 kg/m²), and obese (≥ 30 kg/m²)) and current asthma, adjusting for relevant sociodemographic and health factors. Of the 7090 individuals with asthma in this study, 3627 (51.2%) experienced current asthma. The prevalence of current asthma was similar in overweight individuals (PR = 1.00, 95%CI 0.95, 1.05) when compared to those in the underweight/normal weight category, while individuals with obesity had a 5% higher prevalence (PR = 1.05, 95%CI 1.01, 1.10) when compared to those in the underweight/normal weight category. This study provides evidence for the association between obesity and an increased prevalence of current asthma among adults. Weight management, particularly for individuals with obesity, may be an important consideration in asthma control.

PURPOSE: Early-stage breast cancer (ESBC) in women younger than 50 years often presents with tumor features, including grade and hormone receptor and human epidermal growth factor receptor 2 (HER2) status different from older women. Machine learning clustering techniques can reveal underlying patterns in the inter-relationships of these features and provide novel insights to inform and guide decision making by patients and providers. METHODS: Partitioning around medoids (PAM) was applied to SEER data from 67,746 women age 18-49 years diagnosed with ESBC. PAM clustering based on tumor size (T), nodal status (N), grade, and receptor status identified 10 distinct clusters. The PAM clusters and American Joint Committee on Cancer (AJCC) anatomic and prognostic stages were compared in terms of their tumor features and their association with chemotherapy and survival. RESULTS: AJCC anatomic and prognostic stages are primarily defined by T and N. PAM clusters were primarily defined by receptor status and grade. PAM clusters align closely with luminal A, luminal B, triple-negative, or HER2-overexpressing treatment-related subtypes. PAM clusters better discriminated chemotherapy treatment, with C-statistic 0.839 (95% CI, 0.836 to 0.842), than either anatomic, with C-statistic 0.770 (95% CI, 0.767 to 0.773), or prognostic staging, with C-statistic 0.796 (95% CI, 0.794 to 0.800). PAM clusters were better predictors of 5-year overall survival, with C-statistic 0.733 (95% CI, 0.727 to 0.739), than anatomic stages, with C-statistic 0.721 (95% CI, 0.715 to 728), but not as predictive as prognostic stages, with C-statistic 0.759 (95% CI, 0.753 to 0.764). CONCLUSION: Data-driven PAM clusters provide novel insights into the inter-relationship of tumor features and their association with hormonal, targeted, and chemotherapy treatment and with survival outcomes in women younger than 50 years with ESBC. An online application was created so that the PAM clusters could be used as alternatives or in addition to traditional AJCC staging to inform and guide patients and providers.

While mammography screening programmes improve early detection and reduce mortality for individuals aged 50–74, its extension to those aged 40–49 remains debated. In Canada, breast screening eligibility varies between provinces/territories, with Ontario lowering its eligibility age from 50 to 40 in 2024. This commentary examines recent evidence, including observational studies and simulation models, suggesting that mammography screening from age 40 may offer net benefits. Additionally, using data from Ontario Health (Cancer Care Ontario), we compared stage at diagnosis and 5-year survival rates among 18,639 women aged 40–51 diagnosed with breast cancer (2009–2017). Individuals aged 40–49 had comparable stage at diagnosis and 5-year survival rates to unscreened individuals aged 50–51. Meanwhile, screened individuals aged 50–51 demonstrated the earliest stage at diagnosis and highest 5-year survival rate. Our analysis illustrates the arbitrary nature of an age-based screening threshold at 50. We demonstrate that outcomes for women aged 40–49 resemble those of unscreened women aged 50–51, who were just above the eligibility cutoff. While expanding screening may increase upfront costs, these could be offset by avoiding late-stage treatments and integrating risk-stratified approaches. Overall, women in their 40s may benefit from organized screening programs through earlier detection and improved survival.

Background Population-based breast screening programs diagnose cancers at earlier stage when they are easier to treat. Indeed, individuals screened as part of the Ontario Breast Screening Program (OBSP) are diagnosed with a lower stage of breast cancer than those who have never been screened. We sought to determine if adherence to OBSP guidelines is associated with differences in the rate of death from breast cancer in addition to cancer stage at diagnosis. Methods 48,927 women ≥ 51 years diagnosed with a first primary breast cancer in Ontario 2010–2017 were included and classified as an adherent screener, partial screener, or non-screener. The cohort was developed using administrative health databases linked by Ontario Health. Cause-specific hazard ratios (HR) and 95% confidence intervals (CI) were used to examine the association between adherence to OBSP guidelines and the rate of breast cancer death adjusting for age, rurality, and history of a prior cancer diagnosis. Death from non-breast cancer causes was considered a competing risk. Results Compared to adherent screenings, non-screeners and non-adherent screeners had higher rates of death from breast cancer (HR: 3.59, 95% CI 3.30–3.90 and HR: 1.69, 95% CI 1.47–1.95 respectively). Further, non-adherent screeners (i.e., screened ≥ once) had a lower rate of breast cancer death than non-screeners (HR: 0.47, 95% CI 0.41–0.54). Interpretation Individuals screened in the OBSP have a lower rate of death from breast cancer than non-screeners, even if they are not meeting screening guidelines. These findings suggest women should be encouraged to participate in breast screening regardless of their frequency of use.

This study characterizes trends in contralateral breast cancer (CBC) and contralateral prophylactic mastectomy (CPM) in Ontario, Canada, by breast cancer risk level. Overall, there has been a decline in CBC rates and the concomitant rise in CPM rates after unilateral breast cancer diagnosis, largely driven by high-risk individuals. Considerations for breast cancer risk level are recommended in evaluations of CBC and CPM trends.

PurposeBreast density (BD) and background parenchymal enhancement (BPE) are important imaging biomarkers for breast cancer (BC) risk. We aim to evaluate longitudinal changes in quantitative BD and BPE in high-risk women undergoing dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), focusing on the effects of age and transition into menopause.ApproachA retrospective cohort study analyzed 834 high-risk women undergoing breast DCE-MRI for screening between 2005 and 2020. Quantitative BD and BPE were derived using deep-learning segmentation. Linear mixed-effects models assessed longitudinal changes and the effects of age, menopausal status, weeks since the last menstrual period (LMP-wks), body mass index (BMI), and hormone replacement therapy (HRT) on these imaging biomarkers.ResultsBD decreased with age across all menopausal stages, whereas BPE declined with age in postmenopausal women but remained stable in premenopausal women. HRT elevated BPE in postmenopausal women. Perimenopausal women exhibited decreases in both BD and BPE during the menopausal transition, though cross-sectional age at menopause had no significant effect on either measure. Fibroglandular tissue was positively associated with BPE in perimenopausal women.ConclusionsWe highlight the dynamic impact of menopause on BD and BPE and correlate well with the known relationship between risk and age at menopause. These findings advance the understanding of imaging biomarkers in high-risk populations and may contribute to the development of improved risk assessment leading to personalized chemoprevention and BC screening recommendations.

Many jurisdictions are considering a shift to risk-stratified breast cancer screening; however, evidence on the feasibility of implementing it on a population scale is needed. We conducted a prospective cohort study in the PERSPECTIVE I&I project to produce evidence on risk-stratified breast screening and recruited 3753 participants to undergo multifactorial risk assessment from 2019–2021. This qualitative study explored the perspectives of study personnel on barriers and facilitators to delivering multifactorial risk assessment and risk communication. One focus group and three one-on-one interviews were conducted and a thematic analysis conducted which identified five themes: (1) barriers and facilitators to recruitment for multifactorial risk assessment, (2) barriers and facilitators to completion of the risk factor questionnaire, (3) additional resources required to implement multifactorial risk assessment, (4) the need for a person-centered approach, and (5) and risk literacy. While risk assessment and communication processes were successful overall, key barriers were identified including challenges with collecting comprehensive breast cancer risk factor information and limited resources to execute data collection and risk communication activities on a large scale. Risk assessment and communication processes will need to be optimized for large-scale implementation to ensure they are efficient but robust and person-centered.