Healthcare and Cancer Treatment Costs of Breast Screening Outcomes among Higher than Average Risk Women.

Concurrent cohorts of 644,932 women aged 50-74 screened annually due to family history, dense breasts or biennially in the Ontario Breast Screening Program (OBSP) from 2011-2014 were linked to provincial administrative datasets to determine health system resource utilization and costs. Age-adjusted mean and median total healthcare costs (2018 CAD) and incremental cost differences were calculated by screening outcome and compared by recommendation using regression models. Healthcare costs were compared overall and 1 year after a false positive (n = 46,081) screening mammogram and 2 years after a breast cancer diagnosis (n = 6011). Mean overall healthcare costs by age were highest for those 60-74, particularly with annual screening for family/personal history (CAD 5425; 95% CI: 5308 to 5557) compared to biennial. Although the mean incremental cost difference was higher (23.4%) by CAD 10,235 (95% CI: 6141 to 14,329) per breast cancer for women screened annually for density ≥ 75% compared to biennially, the cost difference was 12.0% lower (-CAD 461; 95% CI: -777 to -114) per false positive result. In contrast, for women screened annually for family/personal history, the mean cost difference per false positive was 19.7% higher than for biennially (CAD 758; 95% CI: 404 to 1118); however, the cost difference per breast cancer was only slightly higher (2.5%) by CAD 1093 (95% CI: -1337 to CAD 3760). Understanding that associated costs of annual compared to biennial screening may balance out by age and outcome can assist decision-making regarding the use of limited healthcare resources.

Validation of the International Breast Cancer Intervention Study (IBIS) model in the High Risk Ontario Breast Screening Program: A retrospective cohort study.

PURPOSE: Women with a remaining lifetime risk of breast cancer of ≥25%, estimated using the International Breast Cancer Intervention Study (IBIS) model, were eligible for the High Risk Ontario Breast Screening Program. This study examined the performance of IBIS 10-year risk estimates in the program. METHODS: This retrospective study included 7487 women aged 30 to 69 years referred to the High Risk Ontario Breast Screening Program between July 1, 2011, and December 31, 2016, with follow-up until December 31, 2018. Model calibration and discrimination were assessed. Analyses were conducted overall and stratified by age (< or ≥50 years). Different 10-year risk thresholds were compared with the current eligibility criteria. RESULTS: Overall, IBIS overestimated the risk of breast cancer with an expected vs observed case ratio of 1.17 (95% CI = 1.04-1.35). Overestimation was highest in women aged 50 to 69 years (expected vs observed case ratio = 1.29, 95% CI = 1.03-1.69) and for those in the top quartile of risk. Overall discrimination was fair with a concordance statistic of 0.66 (95% CI = 0.63-0.70). Furthermore, when using different 10-year risk eligibility thresholds, most cases would have been missed in the 30 to 49 age group using the 8% 10-year risk threshold, whereas relatively few women aged 50 to 69 would have been ineligible at any of the thresholds examined. CONCLUSION: We found that IBIS overestimated the risk of breast cancer in this screening cohort but had adequate discrimination. Age-specific risk thresholds should be considered to optimize the program eligibility criteria.

Incorporating Alternative Polygenic Risk Scores into the BOADICEA Breast Cancer Risk Prediction Model.

BACKGROUND: The multifactorial risk prediction model BOADICEA enables identification of women at higher or lower risk of developing breast cancer. BOADICEA models genetic susceptibility in terms of the effects of rare variants in breast cancer susceptibility genes and a polygenic component, decomposed into an unmeasured and a measured component - the polygenic risk score (PRS). The current version was developed using a 313 SNP PRS. Here, we evaluated approaches to incorporating this PRS and alternative PRS in BOADICEA. METHODS: The mean, SD, and proportion of the overall polygenic component explained by the PRS (α2) need to be estimated. $\alpha $ was estimated using logistic regression, where the age-specific log-OR is constrained to be a function of the age-dependent polygenic relative risk in BOADICEA; and using a retrospective likelihood (RL) approach that models, in addition, the unmeasured polygenic component. RESULTS: Parameters were computed for 11 PRS, including 6 variations of the 313 SNP PRS used in clinical trials and implementation studies. The logistic regression approach underestimates $\alpha $, as compared with the RL estimates. The RL $\alpha $ estimates were very close to those obtained by assuming proportionality to the OR per 1 SD, with the constant of proportionality estimated using the 313 SNP PRS. Small variations in the SNPs included in the PRS can lead to large differences in the mean. CONCLUSIONS: BOADICEA can be readily adapted to different PRS in a manner that maintains consistency of the model. IMPACT: : The methods described facilitate comprehensive breast cancer risk assessment.

Using Real-World Data to Determine Health System Costs of Ontario Women Screened for Breast Cancer.

Our study was to determine breast cancer screening costs in Ontario, Canada for screenings conducted through a formal (Ontario Breast Screening Program, OBSP) and informal (non-OBSP) screening program using administrative databases. Included women were 49-74 years of age when receiving screening mammograms between 1 January 2013 to 31 December 2019. Each woman was followed for a screening episode with screening and diagnostic components, and costs were calculated as an average cost per woman per month in 2021 Canadian dollars. The final cohort of 1,546,386 women screened had a mean age of 59.4 ± 7.1 years and ~87% were screened via OBSP. The average total cost per woman per month was $136 ± $103, $134 ± $103 and $155 ± $104 for the entire, OBSP and non-OBSP cohorts, respectively. This was further disaggregated into the average total screening cost per month, which was $103 ± $8, $100 ± $4 and $117 ± $9 per woman, and the average total diagnostic cost per woman per month at $219 ± $166, $228 ± $165 and $178 ± $159. for the entire, OBSP and non-OBSP cohorts, respectively. These results indicate similar screening costs across the different cohorts, but higher diagnostic costs for the OBSP cohort.

The association of age at menarche and adult height with mammographic density in the International Consortium of Mammographic Density.

BACKGROUND: Early age at menarche and tall stature are associated with increased breast cancer risk. We examined whether these associations were also positively associated with mammographic density, a strong marker of breast cancer risk. METHODS: Participants were 10,681 breast-cancer-free women from 22 countries in the International Consortium of Mammographic Density, each with centrally assessed mammographic density and a common set of epidemiologic data. Study periods for the 27 studies ranged from 1987 to 2014. Multi-level linear regression models estimated changes in square-root per cent density (√PD) and dense area (√DA) associated with age at menarche and adult height in pooled analyses and population-specific meta-analyses. Models were adjusted for age at mammogram, body mass index, menopausal status, hormone therapy use, mammography view and type, mammographic density assessor, parity and height/age at menarche. RESULTS: In pooled analyses, later age at menarche was associated with higher per cent density (ß√PD = 0.023 SE = 0.008, P = 0.003) and larger dense area (ß√DA = 0.032 SE = 0.010, P = 0.002). Taller women had larger dense area (ß√DA = 0.069 SE = 0.028, P = 0.012) and higher per cent density (ß√PD = 0.044, SE = 0.023, P = 0.054), although the observed effect on per cent density depended upon the adjustment used for body size. Similar overall effect estimates were observed in meta-analyses across population groups. CONCLUSIONS: In one of the largest international studies to date, later age at menarche was positively associated with mammographic density. This is in contrast to its association with breast cancer risk, providing little evidence of mediation. Increased height was also positively associated with mammographic density, particularly dense area. These results suggest a complex relationship between growth and development, mammographic density and breast cancer risk. Future studies should evaluate the potential mediation of the breast cancer effects of taller stature through absolute breast density.

Delivery of Cancer Care in Ontario, Canada, During the First Year of the COVID-19 Pandemic.

Importance: The COVID-19 pandemic has impacted cancer systems worldwide. Quantifying the changes is critical to informing the delivery of care while the pandemic continues, as well as for system recovery and future pandemic planning. Objective: To quantify change in the delivery of cancer services across the continuum of care during the COVID-19 pandemic. Design, Setting, and Participants: This population-based cohort study assessed cancer screening, imaging, diagnostic, treatment, and psychosocial oncological care services delivered in pediatric and adult populations in Ontario, Canada (population 14.7 million), from April 1, 2019, to March 1, 2021. Data were analyzed from May 1 to July 31, 2021. Exposures: COVID-19 pandemic. Main Outcomes and Measures: Cancer service volumes from the first year of the COVID-19 pandemic, defined as April 1, 2020, to March 31, 2021, were compared with volumes during a prepandemic period of April 1, 2019, to March 31, 2020. Results: During the first year of the pandemic, there were a total of 4 476 693 cancer care services, compared with 5 644 105 services in the year prior, a difference of 20.7% fewer services of cancer care, representing a potential backlog of 1 167 412 cancer services. While there were less pronounced changes in systemic treatments, emergency and urgent imaging examinations (eg, 1.9% more parenteral systemic treatments) and surgical procedures (eg, 65% more urgent surgical procedures), major reductions were observed for most services beginning in March 2020. Compared with the year prior, during the first pandemic year, cancer screenings were reduced by 42.4% (-1 016 181 screening tests), cancer treatment surgical procedures by 14.1% (-8020 procedures), and radiation treatment visits by 21.0% (-141 629 visits). Biopsies to confirm cancer decreased by up to 41.2% and surgical cancer resections by up to 27.8% during the first pandemic wave. New consultation volumes also decreased, such as for systemic treatment (-8.2%) and radiation treatment (-9.3%). The use of virtual cancer care increased for systemic treatment and radiation treatment and psychosocial oncological care visits, increasing from 0% to 20% of total new or follow-up visits prior to the pandemic up to 78% of total visits in the first pandemic year. Conclusions and Relevance: In this population-based cohort study in Ontario, Canada, large reductions in cancer service volumes were observed. While most services recovered to prepandemic levels at the end of the first pandemic year, a substantial care deficit likely accrued. The anticipated downstream morbidity and mortality associated with this deficit underscore the urgent need to address the backlog and recover cancer care and warrant further study.

Differences in breast cancer diagnosis by patient presentation in Ontario: a retrospective cohort study.

BACKGROUND: In Ontario, patients with breast cancer typically receive their diagnoses through the Ontario Breast Screening Program (OBSP) after an abnormal screen, through screening initiated by a primary care provider or other referring physician, or through follow-up of symptoms by patients' primary care providers. We sought to explore the association of the route to diagnosis (screening within or outside the OBSP or via symptomatic presentation) with use of OBSP-affiliated breast assessment sites (O-BAS), wait times until diagnosis or treatment, health care use and overall survival for patients with breast cancer. METHODS: In this retrospective cohort study, we used the Ontario Cancer Registry to identify adults (aged 18-105 yr) who received a diagnosis of breast cancer from 2013 to 2017. We excluded patients if they were not Ontario residents or had missing age or sex, or who died before diagnosis. We used logistic regression to evaluate factors associated with categorical variables (whether patients were or were not referred to an OBAS, whether patients were screened or symptomatic) and Cox proportional hazards regression to identify factors associated with all-cause mortality. RESULTS: Of 51 460 patients with breast cancer, 42 598 (83%) received their diagnoses at an O-BAS. Patients whose cancer was first detected through the OBSP were more likely than symptomatic patients to be given a diagnosis at an O-BAS (adjusted odds ratio 1.68, 95% confidence interval [CI] 1.57 to 1.80). Patients screened by the OBSP were given their diagnoses 1 month earlier than symptomatic patients, but diagnosis at an O-BAS did not affect the time until either diagnosis or treatment. Patients referred to an O-BAS had significantly better overall survival than those who were not referred (adjusted hazard ratio 0.73, 95% CI 0.66 to 0.80). INTERPRETATION: Patients screened through the OBSP were given their diagnoses earlier than symptomatic patients and were more likely to be referred to an O-BAS, which was associated with better survival. Our findings suggest that individuals with signs and symptoms of breast cancer would benefit from similar referral processes, oversight and standards to those used by the OBSP.

Annual Mammographic Screening Reduces the Risk of Interval or Higher Stage Invasive Breast Cancers Among Postmenopausal Women in the Ontario Breast Screening Program.

Purpose: In the Ontario Breast Screening Program (OBSP) annual screening improved breast cancer detection for women 50-74 years with a family/personal history compared to biennial, while detection was equivalent for women screened annually for mammographic density ≥75%. This study compares the risk of interval or higher stage invasive cancers among postmenopausal women screened annually vs biennially by age and estrogen use. Methods: A retrospective design identified 4247 invasive breast cancers diagnosed among concurrent cohorts of women 50-74 screened in the OBSP with digital mammography between 2011 and 2014, followed until 2016. Polytomous logistic regression estimated the risk of interval or higher stage breast cancers by age and estrogen use between women screened annually because of first-degree relative with breast or ovarian cancer or personal history of ovarian cancer, or mammographic density ≥75%, and those screened biennially. Results: The risk of interval vs screen-detected cancers was significantly reduced in women screened annually for family/personal history (OR=.64; 95%CI:0.51-.80), particularly those 60-74 years (OR=.59; 95%CI:0.45-.77) or not currently using estrogen (OR=.66; 95%CI:0.52-.83) compared to those screened biennially. The risk of stage II-IV vs stage I tumors was also lower in women 60-74 years screened annually for family/personal history (OR=.79; 95%CI:0.64-.97) and in those screened annually for mammographic density ≥75% currently using estrogen (OR=.51; 95%CI:0.26-1.01) compared to women screened biennially. Conclusion: Postmenopausal women at increased risk screened annually had equivalent or reduced risks of interval or higher stage invasive breast cancers than those screened biennially, further supporting risk-based screening in this population.

The Impact of Radiologist Screening Mammogram Reading Volume on Performance in the Ontario Breast Screening Program.

PURPOSE: Although some studies have shown increasing radiologists' mammography volumes improves performance, there is a lack of evidence specific to digital mammography and breast screening program performance targets. This study evaluates the relationship between digital screening volume and meeting performance targets. METHODS: This retrospective cohort study included 493 radiologists in the Ontario Breast Screening Program who interpreted 1,762,173 screening mammograms in participants ages 50-90 between 2014 and 2016. Associations between annual screening volume and meeting performance targets for abnormal call rate, positive predictive value (PPV), invasive cancer detection rate (CDR), sensitivity, and specificity were modeled using mixed-effects multivariate logistic regression. RESULTS: Most radiologists read 500-999 (36.7%) or 1,000-1,999 (31.0%) screens annually, and 18.5% read ≥2,000. Radiologists who read ≥2,000 annually were more likely to meet abnormal call rate (OR = 3.85; 95% CI: 1.17-12.61), PPV (OR = 5.36; 95% CI: 2.53-11.34), invasive CDR (OR = 4.14; 95% CI: 1.50-11.46), and specificity (OR = 4.07; 95% CI: 1.89-8.79) targets versus those who read 100-499 screens. Radiologists reading 1,000-1,999 screens annually were more likely to meet PPV (OR = 2.32; 95% CI: 1.22-4.40), invasive CDR (OR = 3.36; 95% CI: 1.49-7.59) and specificity (OR = 2.00; 95% CI: 1.04-3.84) targets versus those who read 100-499 screens. No significant differences were observed for sensitivity. CONCLUSIONS: Annual reading volume requirements of 1,000 in Canada are supported as screening volume above 1,000 was strongly associated with achieving performance targets for nearly all measures. Increasing the minimum volume to 2,000 may further reduce the potential limitations of screening due to false positives, leading to improvements in overall breast screening program quality.

Breast Density and Risk of Interval Cancers: The Effect of Annual Versus Biennial Screening Mammography Policies in Canada.

Regular screening mammography reduces breast cancer mortality. However, in women with dense breasts, the performance of screening mammography is reduced, which is reflected in higher interval cancer rates (ICR). In Canada, population-based screening mammography programs generally screen women biennially; however, some provinces and territories offer annual mammography for women with dense breast tissue routinely and/or on recommendation of the radiologist. This study compared the ICRs in those breast screening programs with a policy of annual vs. those with biennial screening for women with dense breasts. Among 148,575 women with dense breasts screened between 2008 to 2010, there were 288 invasive interval breast cancers; screening programs with policies offering annual screening for women with dense breasts had fewer interval cancers 63/70,814 (ICR 0.89/1000, 95% CI: 0.67-1.11) compared with those with policies of usual biennial screening 225/77,761 (ICR 1.45 /1000 (annualized), 95% CI: 1.19-1.72) i.e. 63% higher (p = 0.0016). In screening programs where radiologists' screening recommendations were able to be analyzed, a total of 76,103 women were screened, with 87 interval cancers; the ICR was lower for recommended annual (65/69,650, ICR 0.93/1000, 95% CI: 0.71, 1.16) versus recommended biennial screening (22/6,453, ICR 1.70/1000 (annualized), 95%CI: 0.70, 2.71)(p = 0.0605). Screening program policies of annual as compared with biennial screening in women with dense breasts had the greatest impact on reducing interval cancer rates. We review our results in the context of current dense breast notification in Canada.

Adherence to guidance for prioritizing higher risk groups for breast cancer screening during the COVID-19 pandemic in the Ontario Breast Screening Program: a descriptive study.

BACKGROUND: Breast cancer screening in Ontario, Canada, was deferred during the first wave of the COVID-19 pandemic, and a prioritization framework to resume services according to breast cancer risk was developed. The purpose of this study was to assess the impact of the pandemic within the Ontario Breast Screening Program (OBSP) by comparing total volumes of screening mammographic examinations and volumes of screening mammographic examinations with abnormal results before and during the pandemic, and to assess backlogs on the basis of adherence to the prioritization framework. METHODS: A descriptive study was conducted among women aged 50 to 74 years at average risk and women aged 30 to 69 years at high risk, who participated in the OBSP. Percentage change was calculated by comparing observed monthly volumes of mammographic examinations from March 2020 to March 2021 with 2019 volumes and proportions by risk group. We plotted estimates of backlog volumes of mammographic examinations by risk group, comparing pandemic with prepandemic screening practices. Volumes of mammographic examinations with abnormal results were plotted by risk group. RESULTS: Volumes of mammographic examinations in the OBSP showed the largest declines in April and May 2020 (> 99% decrease) and returned to prepandemic levels as of March 2021, with an accumulated backlog of 340 876 examinations. As of March 2021, prioritization had reduced the backlog volumes of screens for participants at high risk for breast cancer by 96.5% (186 v. 5469 expected) and annual rescreens for participants at average risk for breast cancer by 13.5% (62 432 v. 72 202 expected); there was a minimal decline for initial screens. Conversely, the backlog increased by 7.6% for biennial rescreens (221 674 v. 206 079 expected). More than half (59.4%) of mammographic examinations with abnormal results were for participants in the higher risk groups. INTERPRETATION: Prioritizing screening for those at higher risk for breast cancer may increase diagnostic yield and redirect resources to minimize potential long-term harms caused by the pandemic. This further supports the clinical utility of risk-stratified cancer screening.

Should Age-Dependent Absolute Risk Thresholds Be Used for Risk Stratification in Risk-Stratified Breast Cancer Screening?

In risk-stratified cancer screening, multiple risk factors are incorporated into the risk assessment. An individual's estimated absolute cancer risk is linked to risk categories with tailored screening recommendations for each risk category. Absolute risk, expressed as either remaining lifetime risk or shorter-term (five- or ten-year) risk, is estimated from the age at assessment. These risk estimates vary by age; however, some clinical guidelines (e.g., enhanced breast cancer surveillance guidelines) and ongoing personalised breast screening trials, stratify women based on absolute risk thresholds that do not vary by age. We examine an alternative approach in which the risk thresholds used for risk stratification vary by age and consider the implications of using age-independent risk thresholds on risk stratification. We demonstrate that using an age-independent remaining lifetime risk threshold approach could identify high-risk younger women but would miss high-risk older women, whereas an age-independent 5-year or 10-year absolute risk threshold could miss high-risk younger women and classify lower-risk older women as high risk. With risk misclassification, women with an equivalent risk level would be offered a different screening plan. To mitigate these problems, age-dependent absolute risk thresholds should be used to inform risk stratification.

Risk-Stratified Approach to Breast Cancer Screening in Canada: Women's Knowledge of the Legislative Context and Concerns about Discrimination from Genetic and Other Predictive Health Data.

The success of risk-stratified approaches in improving population-based breast cancer screening programs depends in no small part on women's buy-in. Fear of genetic discrimination (GD) could be a potential barrier to genetic testing uptake as part of risk assessment. Thus, the objective of this study was twofold. First, to evaluate Canadian women's knowledge of the legislative context governing GD. Second, to assess their concerns about the possible use of breast cancer risk levels by insurance companies or employers. We use a cross-sectional survey of 4293 (age: 30-69) women, conducted in four Canadian provinces (Alberta, British Colombia, Ontario and Québec). Canadian women's knowledge of the regulatory framework for GD is relatively limited, with some gaps and misconceptions noted. About a third (34.7%) of the participants had a lot of concerns about the use of their health information by employers or insurers; another third had some concerns (31.9%), while 20% had no concerns. There is a need to further educate and inform the Canadian public about GD and the legal protections that exist to prevent it. Enhanced knowledge could facilitate the implementation and uptake of risk prediction informed by genetic factors, such as the risk-stratified approach to breast cancer screening that includes risk levels.

Measuring the impact of the COVID-19 pandemic on organized cancer screening and diagnostic follow-up care in Ontario, Canada: A provincial, population-based study.

It is essential to quantify the impacts of the COVID-19 pandemic on cancer screening, including for vulnerable sub-populations, to inform the development of evidence-based, targeted pandemic recovery strategies. We undertook a population-based retrospective observational study in Ontario, Canada to assess the impact of the pandemic on organized cancer screening and diagnostic services, and assess whether patterns of cancer screening service use and diagnostic delay differ across population sub-groups during the pandemic. Provincial health databases were used to identify age-eligible individuals who participated in one or more of Ontario's breast, cervical, colorectal, and lung cancer screening programs from January 1, 2019-December 31, 2020. Ontario's screening programs delivered 951,000 (-41%) fewer screening tests in 2020 than in 2019 and volumes for most programs remained more than 20% below historical levels by the end of 2020. A smaller percentage of cervical screening participants were older (50-59 and 60-69 years) during the pandemic when compared with 2019. Individuals in the oldest age groups and in lower-income neighborhoods were significantly more likely to experience diagnostic delay following an abnormal breast, cervical, or colorectal cancer screening test during the pandemic, and individuals with a high probability of living on a First Nation reserve were significantly more likely to experience diagnostic delay following an abnormal fecal test. Ongoing monitoring and management of backlogs must continue. Further evaluation is required to identify populations for whom access to cancer screening and diagnostic care has been disproportionately impacted and quantify impacts of these service disruptions on cancer incidence, stage, and mortality. This information is critical to pandemic recovery efforts that are aimed at achieving equitable and timely access to cancer screening-related care.

Women's Views on Multifactorial Breast Cancer Risk Assessment and Risk-Stratified Screening: A Population-Based Survey from Four Provinces in Canada.

Risk-stratified screening for breast cancer (BC) is increasingly considered as a promising approach. However, its implementation is challenging and needs to be acceptable to women. We examined Canadian women's attitudes towards, comfort level about, and willingness to take part in BC risk-stratified screening. We conducted an online survey in women aged 30 to 69 years in four Canadian provinces. In total, 4293 women completed the questionnaire (response rate of 63%). The majority of women (63.5% to 72.8%) expressed favorable attitudes towards BC risk-stratified screening. Most women reported that they would be comfortable providing personal and genetic information for BC risk assessment (61.5% to 67.4%) and showed a willingness to have their BC risk assessed if offered (74.8%). Most women (85.9%) would also accept an increase in screening frequency if they were at higher risk, but fewer (49.3%) would accept a reduction in screening frequency if they were at lower risk. There were few differences by province; however, outcomes varied by age, education level, marital status, income, perceived risk, history of BC, prior mammography, and history of genetic test for BC (all p ≤ 0.01). Risk-based BC screening using multifactorial risk assessment appears to be acceptable to most women. This suggests that the implementation of this approach is likely to be well-supported by Canadian women.

Influence of Preexisting Diabetes on Survival After a Breast Cancer Diagnosis in First Nations Women in Ontario, Canada.

PURPOSE: Survival after a breast cancer diagnosis is poorer in First Nations women with a preexisting comorbidity compared with comorbidity-free First Nations women in Ontario, Canada. Given the high prevalence of diabetes in this population, it is important to determine whether preexisting diabetes is related to poorer survival after a breast cancer diagnosis. METHODS: All First Nations women were identified from a cohort of First Nations people diagnosed with breast cancer in diagnostic periods-1995 to 1999 and 2000 to 2004-and seen at a regional cancer program (RCP) in Ontario. Preexisting diabetes status and other factors, such as age at diagnosis, body mass index, and stage at diagnosis, were collected from medical charts at the regional cancer programs. The association between preexisting diabetes and First Nations status was examined by each of the demographic, personal, tumor, and treatment factors using logistic regression models. Survival was compared between First Nations women with (n = 67) and without (n = 215) preexisting diabetes, adjusted by significant study factors using a Cox proportional hazards regression model. RESULTS: The 5-year survival rate among First Nations women with diabetes was 59.8% versus 78.7% among those without diabetes (P < .01). Preexisting diabetes significantly increased the risk of death among First Nations women with breast cancer (hazard ratio, 1.87; 95% CI, 1.12 to 3.13) after adjustment for age group, period of diagnosis, body mass index, other comorbidities at diagnosis, and stage. CONCLUSION: This study recommends awareness of this survival discrepancy among the treatment team for First Nations patients with breast cancer with preexisting diabetes.

Annual vs Biennial Screening: Diagnostic Accuracy Among Concurrent Cohorts Within the Ontario Breast Screening Program.

BACKGROUND: The Ontario Breast Screening Program recommends annual mammography to women age 50-74 years at increased risk because of family history of breast or ovarian cancer or personal history of ovarian cancer or mammographic density 75% or greater. Few studies have examined the diagnostic accuracy of recommendations based on risk factors and included screen film as well as digital mammography. METHODS: A retrospective design identified concurrent cohorts of women age 50-74 years screened annually or biennially with digital mammography only between 2011 and 2014 and followed until 2016 or breast cancer diagnosis. Diagnostic accuracy measures were compared between women screened annually because of first-degree relative of breast or ovarian cancer or personal history of ovarian cancer (n = 67 795 women), mammographic density 75% or greater (n = 51 956), or both (n = 3758) and those screened biennially (n = 526 815). The association between recommendation and sensitivity and specificity was assessed using generalized estimating equation models. All P values are two-sided. RESULTS: For annual screening because of family or personal history vs biennial, sensitivity was statistically significantly higher (81.7% vs 70.6%; OR = 1.86, 95% CI = 1.48 to 2.34), particularly for invasive cancers and postmenopausal women. Although there was no statistically significant difference in sensitivity for annual screening for mammographic density 75% or greater, specificity was statistically significantly lower (91.3%; OR = 0.87, 95% CI = 0.80 to 0.96) vs biennial (92.3%), particularly for women age 50-59 years. CONCLUSION: Compared with biennial screening, annual screening improved detection for women with a family or personal history of breast and/or ovarian cancer, supporting screening that is more frequent. The benefit for annual screening for women with higher mammographic density must be weighed against possible harms of increased false positives.

Performance Measures of Magnetic Resonance Imaging Plus Mammography in the High Risk Ontario Breast Screening Program.

BACKGROUND: The Ontario Breast Screening Program expanded in July 2011 to screen high-risk women age 30-69 years with annual magnetic resonance imaging (MRI) and digital mammography. This study examined the benefits of screening with mammography and MRI by age and risk criteria. METHODS: This prospective cohort study included 8782 women age 30-69 years referred to the High Risk Ontario Breast Screening Program from July 2011 to June 2015, with final results to December 2016. Cancer detection rates, sensitivity, and specificity of MRI and mammography combined were compared with each modality individually within risk groups stratified by age using generalized estimating equation models. Prognostic features of screen-detected breast cancers were compared by modality using Fisher exact test. All P values are two-sided. RESULTS: Among 20 053 screening episodes, there were 280 screen-detected breast cancers (cancer detection rate = 14.0 per 1000, 95% confidence interval [CI] = 12.4 to 15.7). The sensitivity of mammography was statistically significantly lower than that of MRI plus mammography (40.8%, 95% CI = 29.3% to 53.5% vs 96.0%, 95% CI = 92.2% to 98.0%, P < .001). In mutation carriers age 30-39 years, sensitivity of the combination was comparable with MRI alone (100.0% vs 96.8%, 95% CI = 79.2% to 100.0%, P = .99) but with statistically significantly decreased specificity (78.0%, 95% CI = 74.7% to 80.9% vs 86.2%, 95% CI = 83.5% to 88.5%, P < .001). In women age 50-69 years, combining MRI and mammography statistically significantly increased sensitivity compared with MRI alone (96.3%, 95% CI = 90.6% to 98.6% vs 90.9%, 95% CI = 83.6% to 95.1%, P = .02), with a small but statistically significant decrease in specificity (84.2%, 95% CI = 83.1% to 85.2% vs 90.0%, 95% CI = 89.2% to 90.9%, P < .001). CONCLUSIONS: Screening high risk women age 30-39 years with annual MRI only may be sufficient for cancer detection and should be evaluated further, particularly for mutation carriers. Among women age 50-69 years, detection is most effective when mammography is included with annual MRI.

Breast cancer risk and breast screening for trans people: an integration of 3 systematic reviews.

BACKGROUND: Trans people face uncertain risk for breast cancer and barriers to accessing breast screening. Our objectives were to identify and synthesize primary research evidence on the effect of cross-sex hormones (CSHs) on breast cancer risk, prognosis and mortality among trans people, the benefits and harms of breast screening in this population, and existing clinical practice recommendations on breast screening for trans people. METHODS: We conducted 2 systematic reviews of primary research, 1 on the effect of CSHs on breast cancer risk, prognosis and mortality, and the other on the benefits and harms of breast screening, and a third systematic review of guidelines on existing screening recommendations for trans people. We searched PubMed, MEDLINE, Embase, CINAHL, the Cochrane Database of Systematic Reviews and grey literature sources for primary research, guidelines and position statements published in English between 1997 and 2017. Citations were screened by 2 independent reviewers. One reviewer extracted data and assessed methodological quality of included articles; a second reviewer verified these in full. The results were synthesized narratively. RESULTS: Four observational studies, 6 guidelines and 5 position statements were included. Observational evidence of very low certainty did not show an effect of CSHs on breast cancer risk in trans men or trans women. Among trans women, painfulness of mammography and ultrasonography was low. There was no evidence on the effect of CSHs on breast cancer prognosis and mortality, or on benefits and other harms of screening. Existing clinical practice documents recommended screening for distinct trans subpopulations; however, recommendations varied. INTERPRETATION: The limited evidence does not show an effect of CSHs on breast cancer risk. Although there is insufficient evidence to determine the potential benefits and harms of breast screening, existing clinical practice documents generally recommend screening for trans people; further large-scale prospective comparative research is needed.

Comparison of wait times across the breast cancer treatment pathway among screened women undergoing organized breast assessment versus usual care.

OBJECTIVE: The benefit of organized breast assessment on wait times to treatment among asymptomatic women is unknown. The Ontario Breast Screening Program (OBSP) offers screening and organized assessment through Breast Assessment Centres (BAC). This study compares wait times across the treatment pathway among screened women diagnosed with breast cancer through BAC and usual care (UC). METHODS: A retrospective design identified two concurrent cohorts of postmenopausal women aged 50-69 within the OBSP diagnosed with screen-detected invasive breast cancer and assessed in BAC (n = 2010) and UC (n = 1844) between 2002 and 2010. Demographic characteristics were obtained from the OBSP. Medical chart abstraction provided prognostic and treatment data. Multinomial logistic regression examined associations of assessment type with wait times from abnormal mammogram to surgery, chemotherapy or radiotherapy. RESULTS: Compared with through UC, postmenopausal women diagnosed through BAC were significantly less likely to have longer wait times (days) from an abnormal mammogram to definitive surgery (> 89 vs. ≤ 47; OR = 0.63; 95% CI = 0.52-0.77), from final surgery to radiotherapy (> 88 vs. ≤ 55; OR = 0.71; 95% CI = 0.54-0.93) and from final chemotherapy to radiotherapy (> 41 vs. ≤ 28; OR = 0.52; 95% CI = 0.36-0.76). Conversely, women assessed through BAC compared with through UC were more likely to experience longer wait times from final surgery to chemotherapy (> 64 vs. ≤ 40; OR = 1.49; 95% CI = 1.04-2.14). CONCLUSION: Shorter wait times to most treatments for postmenopausal women diagnosed in BAC further supports that women with an abnormal mammogram should be managed through organized assessment. Continued evaluation of factors influencing wait times to treatment is essential for quality improvement and patient outcomes.