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.

Canadian Healthcare Professionals' Views and Attitudes toward Risk-Stratified Breast Cancer Screening.

Given the controversy over the effectiveness of age-based breast cancer (BC) screening, offering risk-stratified screening to women may be a way to improve patient outcomes with detection of earlier-stage disease. While this approach seems promising, its integration requires the buy-in of many stakeholders. In this cross-sectional study, we surveyed Canadian healthcare professionals about their views and attitudes toward a risk-stratified BC screening approach. An anonymous online questionnaire was disseminated through Canadian healthcare professional associations between November 2020 and May 2021. Information collected included attitudes toward BC screening recommendations based on individual risk, comfort and perceived readiness related to the possible implementation of this approach. Close to 90% of the 593 respondents agreed with increased frequency and earlier initiation of BC screening for women at high risk. However, only 9% agreed with the idea of not offering BC screening to women at very low risk. Respondents indicated that primary care physicians and nurse practitioners should play a leading role in the risk-stratified BC screening approach. This survey identifies health services and policy enhancements that would be needed to support future implementation of a risk-stratified BC screening approach in healthcare systems in Canada and other countries.

Polygenic risk scores and risk-stratified breast cancer screening: Familiarity and perspectives of health care professionals.

PURPOSE: Health care professionals are expected to take on an active role in the implementation of risk-based cancer prevention strategies. This study aimed to explore health care professionals' (1) self-reported familiarity with the concept of polygenic risk score (PRS), (2) perceived level of knowledge regarding risk-stratified breast cancer (BC) screening, and (3) preferences for continuing professional development. METHODS: A cross-sectional survey was conducted using a bilingual-English/French-online questionnaire disseminated by health care professional associations across Canada between November 2020 and May 2021. RESULTS: A total of 593 professionals completed more than 2 items and 453 responded to all questions. A total of 432 (94%) participants were female, 103 (22%) were physicians, and 323 (70%) were nurses. Participants reported to be unfamiliar with (20%), very unfamiliar (32%) with, or did not know (41%) the concept of PRS. Most participants reported not having enough knowledge about risk-stratified BC screening (61%) and that they would require more training (77%). Online courses and webinar conferences were the preferred continuing professional development modalities. CONCLUSION: The study indicates that health care professionals are currently not familiar with the concept of PRS or a risk-stratified approach for BC screening. Online information and training seem to be an essential knowledge transfer modality.

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.

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.

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.

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.

Predictors of mammographic density among women with a strong family history of breast cancer.

BACKGROUND: Mammographic density is one of the strongest risk factors for breast cancer. In the general population, mammographic density can be modified by various exposures; whether this is true for women a strong family history is not known. Thus, we evaluated the association between reproductive, hormonal, and lifestyle risk factors and mammographic density among women with a strong family history of breast cancer but no BRCA1 or BRCA2 mutation. METHODS: We included 97 premenopausal and 59 postmenopausal women (age range: 27-68 years). Risk factor data was extracted from the research questionnaire closest in time to the mammogram performed nearest to enrollment. The Cumulus software was used to measure percent density, dense area, and non-dense area for each mammogram. Multivariate generalized linear models were used to evaluate the relationships between breast cancer risk factors and measures of mammographic density, adjusting for relevant covariates. RESULTS: Among premenopausal women, those who had two live births had a mean percent density of 28.8% vs. 41.6% among women who had one live birth (P=0.04). Women with a high body weight had a lower mean percent density compared to women with a low body weight among premenopausal (17.6% vs. 33.2%; P=0.0006) and postmenopausal women (8.7% vs. 14.7%; P=0.04). Among premenopausal women, those who smoked for 14 years or longer had a lower mean dense area compared to women who smoked for a shorter duration (25.3cm2 vs. 53.1cm2; P=0.002). Among postmenopausal women, former smokers had a higher mean percent density (19.5% vs. 10.8%; P=0.003) and dense area (26.9% vs. 16.4%; P=0.01) compared to never smokers. After applying the Bonferroni correction, the association between body weight and percent density among premenopausal women remained statistically significant. CONCLUSIONS: In this cohort of women with a strong family history of breast cancer, body weight was associated with mammographic density. These findings suggest that mammographic density may explain the underlying relationship between some of these risk factors and breast cancer risk, and lend support for the inclusion of mammographic density into risk prediction models.

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.

Validity of Administrative Databases in Comparison to Medical Charts for Breast Cancer Treatment Data.

OBJECTIVE: Medical chart abstraction is the gold standard for collecting breast cancer treatment data for monitoring and research. A less costly alternative is the use of administrative databases. This study will evaluate administrative data in comparison to medical charts for breast cancer treatment information. STUDY DESIGN AND SETTING: A retrospective cohort design identified 2,401 women in the Ontario Breast Screening Program diagnosed with invasive breast cancer from 2006 to 2009. Treatment data were obtained from the Activity Level Reporting and Canadian Institute of Health Information databases. Medical charts were abstracted at cancer centres. Sensitivity, specificity, positive and negative predictive value, and kappa were calculated for receipt and type of treatment, and agreement was assessed for dates. Logistic regression evaluated factors influencing agreement. RESULTS: Sensitivity and specificity for receipt of radiotherapy (92.0%, 99.3%), chemotherapy (77.7%, 99.2%), and surgery (95.8%, 100%) were high but decreased slightly for specific radiotherapy anatomic locations, chemotherapy protocols, and surgeries. Agreement increased by radiotherapy year (trend test, p < 0.0001). Stage II/III compared to stage I cancer decreased odds of agreement for chemotherapy (OR = 0.66, 95% CI: 0.48-0.91) and increased agreement for partial mastectomy (OR = 3.36, 95% CI: 2.27-4.99). Exact agreement in treatment dates varied from 83.0% to 96.5%. CONCLUSION: Administrative data can be accurately utilized for future breast cancer treatment studies.

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.

Serum osteoprotegerin levels and mammographic density among high-risk women.

PURPOSE: Mammographic density is a risk factor for breast cancer but the mechanism behind this association is unclear. The receptor activator of nuclear factor κB (RANK)/RANK ligand (RANKL) pathway has been implicated in the development of breast cancer. Given the role of RANK signaling in mammary epithelial cell proliferation, we hypothesized this pathway may also be associated with mammographic density. Osteoprotegerin (OPG), a decoy receptor for RANKL, is known to inhibit RANK signaling. Thus, it is of interest to evaluate whether OPG levels modify breast cancer risk through mammographic density. METHODS: We quantified serum OPG levels in 57 premenopausal and 43 postmenopausal women using an enzyme-linked immunosorbent assay (ELISA). Cumulus was used to measure percent density, dense area, and non-dense area for each mammographic image. Subjects were classified into high versus low OPG levels based on the median serum OPG level in the entire cohort (115.1 pg/mL). Multivariate models were used to assess the relationship between serum OPG levels and the measures of mammographic density. RESULTS: Serum OPG levels were not associated with mammographic density among premenopausal women (P ≥ 0.42). Among postmenopausal women, those with low serum OPG levels had higher mean percent mammographic density (20.9% vs. 13.7%; P = 0.04) and mean dense area (23.4 cm2 vs. 15.2 cm2; P = 0.02) compared to those with high serum OPG levels after covariate adjustment. CONCLUSIONS: These findings suggest that low OPG levels may be associated with high mammographic density, particularly in postmenopausal women. Targeting RANK signaling may represent a plausible, non-surgical prevention option for high-risk women with high mammographic density, especially those with low circulating OPG levels.

The association of mammographic density with risk of contralateral breast cancer and change in density with treatment in the WECARE study.

BACKGROUND: Mammographic density (MD) is an established predictor of risk of a first breast cancer, but the relationship of MD to contralateral breast cancer (CBC) risk is not clear, including the roles of age, mammogram timing, and change with treatment. Multivariable prediction models for CBC risk are needed and MD could contribute to these. METHODS: We conducted a case-control study of MD and CBC risk in phase II of the WECARE study where cases had a CBC diagnosed ≥ 2 years after first diagnosis at age <55 years and controls had unilateral breast cancer (UBC) with similar follow-up time. We retrieved film mammograms of the unaffected breast from two time points, prior to/at the time of the first diagnosis (253 CBC cases, 269 UBC controls) and ≥ 6 months up to 48 months following the first diagnosis (333 CBC cases, 377 UBC controls). Mammograms were digitized and percent MD (%MD) was measured using the thresholding program Cumulus. Odds ratios (OR) and 95% confidence intervals (CI) for association between %MD and CBC, adjusted for age, treatment, and other factors related to CBC, were estimated using logistic regression. Linear regression was used to estimate the association between treatment modality and change in %MD in 467 women with mammograms at both time points. RESULTS: For %MD assessed following diagnosis, there was a statistically significant trend of increasing CBC with increasing %MD (p = 0.03). Lower density (<25%) was associated with reduced risk of CBC compared to 25 to < 50% density (OR 0.69, 95% CI 0.49, 0.98). Similar, but weaker, associations were noted for %MD measurements prior to/at diagnosis. The relationship appeared strongest in women aged < 45 years and non-existent in women aged 50 to 54 years. A decrease of ≥ 10% in %MD between first and second mammogram was associated marginally with reduced risk of CBC (OR 0.63, 95% CI 0.40, 1.01) compared to change of <10%. Both tamoxifen and chemotherapy were associated with statistically significant 3% decreases in %MD (p < 0.01). CONCLUSIONS: Post-diagnosis measures of %MD may be useful to include in CBC risk prediction models with consideration of age at diagnosis. Chemotherapy is associated with reductions in %MD, similar to tamoxifen.

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.

Improved detection of clinically relevant wound bacteria using autofluorescence image-guided sampling in diabetic foot ulcers.

Clinical wound assessment involves microbiological swabbing of wounds to identify and quantify bacterial species, and to determine microbial susceptibility to antibiotics. The Levine swabbing technique may be suboptimal because it samples only the wound bed, missing other diagnostically relevant areas of the wound, which may contain clinically significant bacteria. Thus, there is a clinical need to improve the reliability of microbiological wound sampling. To address this, a handheld portable autofluorescence (AF) imaging device that detects bacteria in real time, without contrast agents, was developed. Here, we report the results of a clinical study evaluating the use of real-time AF imaging to visualise bacteria in and around the wound bed and to guide swabbing during the clinical assessment of diabetic foot ulcers, compared with the Levine technique. We investigated 33 diabetic foot ulcers (n = 31 patients) and found that AF imaging more accurately identified the presence of moderate and/or heavy bacterial load compared with the Levine technique (accuracy 78% versus 52%, P = 0·048; adjusted diagnostic odds ratio 7·67, P < 0·00022 versus 3·07, P = 0·066) and maximised the effectiveness of bacterial load sampling, with no significant impact on clinical workflow. AF imaging may help clinicians better identify the wound areas with clinically significant bacteria, and maximise sampling of treatment-relevant pathogens.

Optically-tracked handheld fluorescence imaging platform for monitoring skin response in the management of soft tissue sarcoma.

Standard clinical management of extremity soft tissue sarcomas includes surgery with radiation therapy. Wound complications (WCs) arising from treatment may occur due to bacterial infection and tissue breakdown. The ability to detect changes in these parameters during treatment may lead to earlier interventions that mitigate WCs. We describe the use of a new system composed of an autofluorescence imaging device and an optical three-dimensional tracking system to detect and coregister the presence of bacteria with radiation doses. The imaging device visualized erythema using white light and detected bacterial autofluorescence using 405-nm excitation light. Its position was tracked relative to the patient using IR reflective spheres and registration to the computed tomography coordinates. Image coregistration software was developed to spatially overlay radiation treatment plans and dose distributions on the white light and autofluorescence images of the surgical site. We describe the technology, its use in the operating room, and standard operating procedures, as well as demonstrate technical feasibility and safety intraoperatively. This new clinical tool may help identify patients at greater risk of developing WCs and investigate correlations between radiation dose, skin response, and changes in bacterial load as biomarkers associated with WCs.

Point-of-care autofluorescence imaging for real-time sampling and treatment guidance of bioburden in chronic wounds: first-in-human results.

BACKGROUND: Traditionally, chronic wound infection is diagnosed by visual inspection under white light and microbiological sampling, which are subjective and suboptimal, respectively, thereby delaying diagnosis and treatment. To address this, we developed a novel handheld, fluorescence imaging device (PRODIGI) that enables non-contact, real-time, high-resolution visualization and differentiation of key pathogenic bacteria through their endogenous autofluorescence, as well as connective tissues in wounds. METHODS AND FINDINGS: This was a two-part Phase I, single center, non-randomized trial of chronic wound patients (male and female, ≥18 years; UHN REB #09-0015-A for part 1; UHN REB #12-5003 for part 2; clinicaltrials.gov Identifier: NCT01378728 for part 1 and NCT01651845 for part 2). Part 1 (28 patients; 54% diabetic foot ulcers, 46% non-diabetic wounds) established the feasibility of autofluorescence imaging to accurately guide wound sampling, validated against blinded, gold standard swab-based microbiology. Part 2 (12 patients; 83.3% diabetic foot ulcers, 16.7% non-diabetic wounds) established the feasibility of autofluorescence imaging to guide wound treatment and quantitatively assess treatment response. We showed that PRODIGI can be used to guide and improve microbiological sampling and debridement of wounds in situ, enabling diagnosis, treatment guidance and response assessment in patients with chronic wounds. PRODIGI is safe, easy to use and integrates into the clinical workflow. Clinically significant bacterial burden can be detected in seconds, quantitatively tracked over days-to-months and their biodistribution mapped within the wound bed, periphery, and other remote areas. CONCLUSIONS: PRODIGI represents a technological advancement in wound sampling and treatment guidance for clinical wound care at the point-of-care. TRIAL REGISTRATION: ClinicalTrials.gov NCT01651845; ClinicalTrials.gov NCT01378728.

The association between breast tissue optical content and mammographic density in pre- and post-menopausal women.

Mammographic density (MD), associated with higher water and lower fat content in the breast, is strongly related to breast cancer risk. Optical attenuation spectroscopy (OS) is a non-imaging method of evaluating breast tissue composition by red and near-infrared light transmitted through the breast that, unlike mammography, does not involve radiation. OS provides information on wavelength dependent light scattering of tissue and on absorption by water, lipid, oxy-, deoxy-hemoglobin. We propose that OS could be an alternative marker of breast cancer risk and that OS breast tissue measures will be associated with MD. In the present analysis, we developed an algorithm to estimate breast tissue composition and light scattering parameters using a spectrally constrained global fitting procedure employing a diffuse light transport model. OS measurements were obtained from 202 pre- and post-menopausal women with normal mammograms. Percent density (PD) and dense area (DA) were measured using Cumulus. The association between OS tissue composition and PD and DA was analyzed using linear regression adjusted for body mass index. Among pre-menopausal women, lipid content was significantly inversely associated with square root transformed PD (ß = -0.05, p = 0.0002) and DA (ß = -0.05, p = 0.019); water content was significantly positively associated with PD (ß = 0.06, p = 0.008). Tissue oxygen saturation was marginally inversely associated with PD (ß = -0.03, p = 0.057) but significantly inversely associated with DA (ß = -0.10, p = 0.002). Among post-menopausal women lipid and water content were significantly associated (negatively and positively, respectively) with PD (ß lipid = -0.08, ß water = 0.14, both p<0.0001) and DA (ß lipid = -0.10, p<0.0001; ß water = 0.11, p = 0.001). The association between OS breast content and PD and DA is consistent with more proliferation in dense tissue of younger women, greater lipid content in low density tissue and higher water content in high density tissue. OS may be useful for assessing physiologic tissue differences related to breast cancer risk, particularly when mammography is not feasible or easily accessible.