Implementing Multifactorial Risk Assessment with Polygenic Risk Scores for Personalized Breast Cancer Screening in the Population Setting: Challenges and Opportunities.

Risk-stratified breast screening has been proposed as a strategy to overcome the limitations of age-based screening. A prospective cohort study was undertaken within the PERSPECTIVE I&I project, which will generate the first Canadian evidence on multifactorial breast cancer risk assessment in the population setting to inform the implementation of risk-stratified screening. Recruited females aged 40-69 unaffected by breast cancer, with a previous mammogram, underwent multifactorial breast cancer risk assessment. The adoption of multifactorial risk assessment, the effectiveness of methods for collecting risk factor information and the costs of risk assessment were examined. Associations between participant characteristics and study sites, as well as data collection methods, were assessed using logistic regression; all p-values are two-sided. Of the 4246 participants recruited, 88.4% completed a risk assessment, with 79.8%, 15.7% and 4.4% estimated at average, higher than average and high risk, respectively. The total per-participant cost for risk assessment was CAD 315. Participants who chose to provide risk factor information on paper/telephone (27.2%) vs. online were more likely to be older (p = 0.021), not born in Canada (p = 0.043), visible minorities (p = 0.01) and have a lower attained education (p < 0.0001) and perceived fair/poor health (p < 0.001). The 34.4% of participants requiring risk factor verification for missing/unusual values were more likely to be visible minorities (p = 0.009) and have a lower attained education (p ≤ 0.006). This study demonstrates the feasibility of risk assessment for risk-stratified screening at the population level. Implementation should incorporate an equity lens to ensure cancer-screening disparities are not widened.

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.

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.

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.

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.

The impact of organized breast assessment on survival by stage for screened women diagnosed with invasive breast cancer.

PURPOSE: Since 1998, the Ontario Breast Screening Program (OBSP) has offered organized assessment through Breast Assessment Centres (BAC). This study compares survival between screened women diagnosed with breast cancer who have undergone assessment through a BAC and usual care (UC). METHODS: A retrospective design identified two concurrent cohorts of women aged 50 to 69 within the OBSP diagnosed with screen-detected invasive breast cancer at a BAC (n = 2010) and UC (n = 1844) between 2002 and 2010 and followed until 2016. Demographic and assessment characteristics were obtained from the OBSP. Abstraction of medical charts provided prognostic and treatment data. Death data were assessed from the Registered Person's Database and the Ontario Registrar General All-Cause Mortality File. Multivariable Cox proportional hazards models compared overall survival by assessment type (BAC/UC), stratified by stage. RESULTS: There were 505 deaths during the study (BAC = 239; UC = 266). Among women with stage I screen-detected breast cancer, those diagnosed through a BAC had 31% reduced risk of all-cause mortality (HR = 0.69, 95% CI = 0.53-0.90) compared to UC. Diagnosis within 7 weeks of an abnormal mammogram reduced the hazard of death from all causes by 34% among all women with stage I breast cancers (HR = 0.66, 95% CI = 0.47-0.91), and was more likely in BAC (79.7%) than UC (66.9%). CONCLUSION: The significant improvement in overall survival for women with stage I screen-detected invasive breast cancer assessed through BACs further supports the recommendation that women with abnormal mammograms should be managed through organized assessment.

Genetic assessment wait time indicators in the High Risk Ontario Breast Screening Program.

BACKGROUND: The Ontario Breast Screening Program (OBSP) expanded in July 2011 to screen high-risk women aged 30-69 with annual MRI and mammography. This study evaluated wait time (WT) indicators along the genetic assessment (GA) pathway for women referred to the High Risk OBSP. METHODS: Information was collected for 27,170 women referred to the High Risk OBSP from July 2011 to June 2015 and followed for GA until June 2016. Median duration (days), interquartile range (IQR) were measured for each WT indicator by program year, age, prior breast cancer, and risk criteria. RESULTS: Among 24,811 women who completed GA, 16,367 (66.0%) had genetic counseling only, 8,444 (34.0%) had counseling and testing and 8,027 (32.4%) met the high risk criteria. Median WT from physician visit to first screen was longer for women having genetic counseling only compared to those having counseling and testing (244 vs. 197 days). Women having counseling only also experienced the longest WT from physician visit to genetic counseling (88 days; IQR = 10-174), which increased by year from 71 to 100 days (p < .0001). Among women having counseling and testing, WT from physician visit to counseling was shortest for mutation carriers (39 days; IQR = 4-100). Median WT from testing to laboratory report issue was 41 days (IQR = 22-70) and 17 days to disclosure of test results (IQR = 7-33). Both WTs decreased with year and were shorter for mutation carriers (33 days, IQR = 19-58; 15 days, IQR = 7-28, respectively). CONCLUSIONS: After implementation of the High Risk OBSP, women received timely genetic counseling, in particular those having counseling and testing. Effective triage models for physicians could reduce WT to GA after physician referral.

Evaluating wait times from screening to breast cancer diagnosis among women undergoing organised assessment vs usual care.

BACKGROUND: Timely coordinated diagnostic assessment following an abnormal screening mammogram reduces patient anxiety and may optimise breast cancer prognosis. Since 1998, the Ontario Breast Screening Program (OBSP) has offered organised assessment through Breast Assessment Centres (BACs). For OBSP women seen at a BAC, an abnormal mammogram is followed by coordinated referrals through the use of navigators for further imaging, biopsy, and surgical consultation as indicated. For OBSP women seen through usual care (UC), further diagnostic imaging is arranged directly from the screening centre and/or through their physician; results must be communicated to the physician who is then responsible for arranging any necessary biopsy and/or surgical consultation. This study aims to evaluate factors associated with diagnostic wait times for women undergoing assessment through BAC and UC. METHODS: Of the 2 147 257 women aged 50-69 years screened in the OBSP between 1 January 2002 and 31 December 2009, 155 866 (7.3%) had an abnormal mammogram. A retrospective design identified two concurrent cohorts of women diagnosed with screen-detected breast cancer at a BAC (n=4217; 47%) and UC (n=4827; 53%). Multivariable logistic regression analyses examined associations between wait times and assessment and prognostic characteristics by pathway. A two-sided 5% significance level was used. RESULTS: Screened women with breast cancer were two times more likely to be diagnosed within 7 weeks when assessed through a BAC vs UC (OR=1.91, 95% CI=1.73-2.10). In addition, compared with UC, women assessed through a BAC were significantly more likely to have their first assessment procedure within 3 weeks of their abnormal mammogram (OR=1.25, 95% CI=1.12-1.39), ⩽3 assessment procedures (OR=1.54, 95% CI=1.41-1.69), ⩽2 assessment visits (OR=1.86, 95% CI=1.70-2.05), and ⩾2 procedures per visit (OR=1.41, 95% CI=1.28-1.55). Women diagnosed through a BAC were also more likely than those in UC to have imaging (OR=1.99, 95% CI=1.44-2.75) or a biopsy (OR=3.69, 95% CI=2.64-5.15) vs consultation only at their first assessment visit, and two times more likely to have a core or FNA biopsy than a surgical biopsy (OR=2.08, 95% CI=1.81-2.40). Having ⩽2 assessment visits was more likely to reduce time to diagnosis for women assessed through a BAC compared with UC (BAC OR=10.58, 95% CI=8.96-12.50; UC OR=4.47, 95% CI=3.94-5.07), as was having ⩽3 assessment procedures (BAC OR=4.97, 95% CI=4.26-5.79; UC OR=2.95, 95% CI=2.61-3.33). Income quintile affected wait times only in women diagnosed in UC, with those in the two highest quintiles more likely to receive a diagnosis in 7 weeks. CONCLUSIONS: Women with screen-detected breast cancer in OBSP were more likely to have shorter wait times if they were diagnosed through organised assessment. This might be as a result of women diagnosed through a BAC having more procedures per visit, procedures scheduled in shorter intervals, and imaging or biopsy on their first visit. Given the significant improvement in timeliness to diagnosis, women with abnormal mammograms should be managed through organised assessment.

Improving work-up of the abnormal mammogram through organized assessment: results from the ontario breast screening program.

PURPOSE: Women with an abnormal screening mammogram should ideally undergo an organized assessment to attain a timely diagnosis. This study evaluated outcomes of women undergoing work-up after abnormal mammogram through a formal breast assessment affiliate (BAA) program with explicit care pathways compared with usual care (UC) using developed quality indicators for screening mammography programs. METHODS: Between January 1 and December 31, 2007, a total of 320,635 women underwent a screening mammogram through the Ontario Breast Screening Program (OBSP), of whom 25,543 had an abnormal result requiring further assessment. Established indicators assessing timeliness, appropriateness of follow-up, and biopsy rates were compared between women who were assessed through either a BAA or UC using χ(2) analysis. RESULTS: Work-up of the abnormal mammogram for patients screened through a BAA resulted in a greater proportion of women attaining a definitive diagnosis within the recommended time interval when a histologic diagnosis was required. In addition, use of other quality measures including specimen radiography for both core biopsies and surgical specimens and preoperative core needle biopsy was greater in BAA facilities. CONCLUSION: These findings support future efforts to increase the number of BAAs within the OBSP, because the pathways and reporting methods associated with them result in improvements in our ability to provide timely and appropriate care for women requiring work-up of an abnormal mammogram.

Effect of screening result on waiting times to assessment and breast cancer diagnosis: results from the Ontario Breast Screening Program.

BACKGROUND: The effect of severity of screening result on delays to diagnosis has primarily been examined for mammographic abnormalities. This study will examine delays to assessment and diagnosis for women with an abnormal mammogram compared to women with an abnormal clinical breast examination (CBE) or abnormal CBE and mammogram. METHODS: Using data routinely collected by Ontario Breast Screening Program (OBSP), 12,675 women aged 50 to 69 with an abnormal screening result between January 1, 2000 and December 31, 2000 were followed prospectively to the completion of their assessment process. Median waiting times from abnormal screen to first assessment procedure and diagnosis were compared by modality of referral and among women with a breast cancer diagnosis by prognostic features. RESULTS: The median waiting time to first assessment and to diagnosis was significantly longer for women with only a clinical abnormality compared to women with a mammographic abnormality. In addition, women diagnosed with cancers of larger size had longer delays when the abnormality was detected only clinically. However, women referred by both modalities had significantly shorter waiting times to first assessment procedure and to diagnosis of poor prognosis cancers compared to women referred by mammography alone. INTERPRETATION: Women with an abnormal CBE and mammogram are assessed more promptly and have shorter diagnostic times. However, women with only a CBE abnormality had delays to diagnosis as a result of longer waiting times to first assessment procedure. Integration of the OBSP with assessment centres should improve times to diagnosis irrespective of modality of referral.