Breast cancer risk assessment and risk distribution in 3,491 Slovenian women invited for screening at the age of 50; a population-based cross-sectional study.

BACKGROUND: The evidence shows that risk-based strategy could be implemented to avoid unnecessary harm in mammography screening for breast cancer (BC) using age-only criterium. Our study aimed at identifying the uptake of Slovenian women to the BC risk assessment invitation and assessing the number of screening mammographies in case of risk-based screening. PATIENTS AND METHODS: A cross-sectional population-based study enrolled 11,898 women at the age of 50, invited to BC screening. The data on BC risk factors, including breast density from the first 3,491 study responders was collected and BC risk was assessed using the Tyrer-Cuzick algorithm (version 8) to classify women into risk groups (low, population, moderately increased, and high risk group). The number of screening mammographies according to risk stratification was simulated. RESULTS: 57% (6,785) of women returned BC risk questionnaires. When stratifying 3,491 women into risk groups, 34.0% were assessed with low, 62.2% with population, 3.4% with moderately increased, and 0.4% with high 10-year BC risk. In the case of potential personalised screening, the number of screening mammographies would drop by 38.6% compared to the current screening policy. CONCLUSIONS: The study uptake showed the feasibility of risk assessment when inviting women to regular BC screening. 3.8% of Slovenian women were recognised with higher than population 10-year BC risk. According to Slovenian BC guidelines they may be screened more often. Overall, personalised screening would decrease the number of screening mammographies in Slovenia. This information is to be considered when planning the pilot and assessing the feasibility of implementing population risk-based screening.

Uncertainty estimation for deep learning-based pectoral muscle segmentation via Monte Carlo dropout.

Objective. Deep Learning models are often susceptible to failures after deployment. Knowing when your model is producing inadequate predictions is crucial. In this work, we investigate the utility of Monte Carlo (MC) dropout and the efficacy of the proposed uncertainty metric (UM) for flagging of unacceptable pectoral muscle segmentations in mammograms.Approach. Segmentation of pectoral muscle was performed with modified ResNet18 convolutional neural network. MC dropout layers were kept unlocked at inference time. For each mammogram, 50 pectoral muscle segmentations were generated. The mean was used to produce the final segmentation and the standard deviation was applied for the estimation of uncertainty. From each pectoral muscle uncertainty map, the overall UM was calculated. To validate the UM, a correlation between the dice similarity coefficient (DSC) and UM was used. The UM was first validated in a training set (200 mammograms) and finally tested in an independent dataset (300 mammograms). ROC-AUC analysis was performed to test the discriminatory power of the proposed UM for flagging unacceptable segmentations.Main results. The introduction of dropout layers in the model improved segmentation performance (DSC = 0.95 ± 0.07 versus DSC = 0.93 ± 0.10). Strong anti-correlation (r= -0.76,p< 0.001) between the proposed UM and DSC was observed. A high AUC of 0.98 (97% specificity at 100% sensitivity) was obtained for the discrimination of unacceptable segmentations. Qualitative inspection by the radiologist revealed that images with high UM are difficult to segment.Significance. The use of MC dropout at inference time in combination with the proposed UM enables flagging of unacceptable pectoral muscle segmentations from mammograms with excellent discriminatory power.

Prognostic factors and outcomes in women with breast cancer in Slovenia in relation to step-wise implementation of organized screening.

INTRODUCTION: The aim of organized breast cancer screening is early detection and reduction in mortality. Organized screening should promote equal access and reduce socio-economic inequalities. In Slovenia, organized breast cancer screening achieved complete coverage in 11-years' time. We explored whether step-wise implementation reflects in prognostic factors (earlier diagnosis and treatment) and survival of breast cancer patients in our population. METHODS: Using population-based cancer registry and screening registry data on breast cancer cases from 2008-2018, we compared stage distribution and mean time to surgical treatment in (A) women who underwent at least one mammography in the organized screening programme, women who received at least one invitation but did not undergo mammography and women who did not receive any screening invitation, and in (B) women who were invited to organized screening and those who were not. We also compared net survival by stage in different groups of women according to their screening programme status. RESULTS: Women who underwent at least one mammography in organized screening had lower disease stage at diagnosis. Time-to-treatment analysis showed mean time to surgery was shortest in women not included in organized screening (all stages = 36.0 days vs. 40.3 days in women included in organized screening). This could be due to quality assurance protocols with an obligatory multidisciplinary approach within the organized screening vs. standard treatment pathways which can vary in different (smaller) hospitals. Higher standard of care in screening is reflected in better survival in women included in organized screening (5-years net survival for regional stage: at least one mammography in the screening programme- 96%; invitation, but no mammography- 87.4%; no invitation or mammography in the screening programme- 82.6%). CONCLUSION: Our study, which is one of the first in central European countries, shows that introduction of organized screening has temporary effects on population cancer burden indicators already during roll-out period, which should therefore be as short as possible.

Quality assured implementation of the Slovenian breast cancer screening programme.

SETTING: The organised, population-based breast cancer screening programme in Slovenia began providing biennial mammography screening for women aged 50-69 in 2008. The programme has taken a comprehensive approach to quality assurance as recommended by the European guidelines for quality assurance in breast cancer screening and diagnosis (4th edition), including centralized assessment, training and supervision, and proactive monitoring of performance indicators. This report describes the progress of implementation and rollout from 2003 through 2019. METHODS: The screening protocol and key quality assurance procedures initiated during the planning from 2003 and rollout from 2008 of the screening programme, including training of the professional staff, are described. The organisational structure, gradual geographical rollout, and coverage by invitation and examination are presented. RESULTS: The nationwide programme was up and running in all screening regions by the end of 2017, at which time the nationwide coverage by invitation and examination had reached 70% and 50%, respectively. Nationwide rollout of the population-based programme was complete by the end of 2019. By this time, coverage by invitation and examination had reached 98% and 76%, respectively. The participation rates consistently exceeded 70% from 2014 to 2019. CONCLUSIONS: The successful implementation of the screening programme can be attributed to an independent central management, external guidance, and strict adherence to quality assurance procedures, all of which contributed to increasing governmental and popular support. The benefits of quality assurance have influenced all aspects of breast care and have provided a successful model for multidisciplinary management of other diseases.

Extending Age Ranges in Breast Cancer Screening in Four European Countries: Model Estimations of Harm-to-Benefit Ratios.

The main benefit of breast cancer (BC) screening is a reduction in mortality from BC. However, screening also causes harms such as overdiagnosis and false-positive results. The balance between benefits and harms varies by age. This study aims to assess how harm-to-benefit ratios of BC screening vary by age in the Netherlands, Finland, Italy and Slovenia. Using microsimulation models, we simulated biennial screening with 100% attendance at varying ages for cohorts of women followed over a lifetime. The number of overdiagnoses, false-positive diagnoses, BC deaths averted and life-years gained (LYG) were calculated per 1000 women. We compared four strategies (50-69, 45-69, 45-74 and 50-74) by calculating four harm-to-benefit ratios, respectively. Compared to the reference strategy 50-69, screening women at 45-74 or 50-74 years would be less beneficial in any of the four countries than screening women at 45-69, which would result in relatively fewer overdiagnoses per death averted or LYG. At the same time, false-positive results per death averted would increase substantially. Adapting the age range of BC screening is an option to improve harm-to-benefit ratios in all four countries. Prioritization of considered harms and benefits affects the interpretation of results.

Performance indicators in breast cancer screening in the European Union: A comparison across countries of screen positivity and detection rates.

Comparable performance indicators for breast cancer screening in the European Union (EU) have not been previously reported. We estimated adjusted breast cancer screening positivity rate (PR) and detection rates (DR) to investigate variation across EU countries. For the age 50-69 years, the adjusted EU-pooled PR for initial screening was 8.9% (cross-programme variation range 3.2-19.5%) while DR of invasive cancers was 5.3/1,000 (range 3.8-7.4/1,000) and DR of ductal carcinoma in situ (DCIS) was 1.3/1,000 (range 0.7-2.7/1,000). For subsequent screening, the adjusted EU-pooled PR was 3.6% (range 1.4-8.4%), the DR was 4.0/1,000 (range 2.2-5.8/1,000) and 0.8/1,000 (range 0.5-1.3/1,000) for invasive and DCIS, respectively. Adjusted performance indicators showed remarkable heterogeneity, likely due to different background breast cancer risk and awareness between target populations, and also different screening protocols and organisation. Periodic reporting of the screening indicators permits comparison and evaluation of the screening activities between and within countries aiming to improve the quality and the outcomes of screening programmes. Cancer Screening Registries would be a milestone in this direction and EU Screening Reports provide a fundamental contribution to building them.

A health systems approach to identifying barriers to breast cancer screening programmes. Methodology and application in six European countries.

The benefits of population-based screening for breast cancer are now accepted although, in practice, programmes often fail to achieve their full potential. In this paper, we propose a conceptual model that situates screening programmes within the broader health system to understand the factors that influence their outcomes. We view the overall screening system as having multiple sub-systems to identify the population at risk, generate knowledge of effectiveness, maximise uptake, operate the programme, and optimise follow-up and assurance of subsequent treatment. Based on this model we have developed the Barriers to Effective Screening Tool (BEST) for analysing government-led, population-based screening programmes from a health systems perspective. Conceived as a self-assessment tool, we piloted the tool with key informants in six European countries (Estonia, Finland, Hungary, Italy, The Netherlands and Slovenia) to identify barriers to the optimal operation of population-based breast cancer screening programmes. The pilot provided valuable feedback on the barriers affecting breast cancer screening programmes and stimulated a greater recognition among those operating them of the need to take a health systems perspective. In addition, the pilot led to further development of the tool and provided a foundation for further research into how to overcome the identified barriers.

Time trends and spatial patterns in the mesothelioma incidence in Slovenia, 1961-2014.

We aimed to explore the temporal and spatial variations in mesothelioma incidence in Slovenia for the last 50 years and, among these, to evaluate the consequences of asbestos usage. The incidence data from the population-based Cancer Registry of Republic of Slovenia for the period 1961-2014 were analysed. The data of asbestos imported to Slovenia were used as a proxy for asbestos exposure in manufacturing areas. Log-linear joinpoint regression and age-period-cohort Poisson models were used in the time-trend analysis. The mesothelioma maps were produced according to the method of local standardized incidence ratio estimates and are presented together with the map of Slovenian major asbestos-exposed locations. The maximum value of the asbestos import curve corresponds to the peak of mesothelioma curve exactly 30 years later. Both increases before the peak are comparable in time interval and steepness. The highest mesothelioma risk was detected for the cohort born between 1940 and 1944. In maps, the mesothelioma clusters manifest around known asbestos sources predominantly in the years 1980-1990, but in the last few years, the geographical distribution is more dispersed. The data from our long-existing population-based cancer registry provide a good insight into the on-going mesothelioma epidemic in Slovenia. Our results imply that the mesothelioma peak has already been reached in Slovenia. In the future, new cases will emerge more randomly throughout the country.

Cancer burden in slovenia with the time trends analysis.

BACKGROUND: The aim of our study was to describe cancer burden and time trends of all cancers combined, the most frequent as well as the rare cancers in Slovenia. PATIENTS AND METHODS: The principal data source was the population-based Cancer Registry of Republic of Slovenia. The cancer burden is presented by incidence and prevalence for the period 1950-2013 and by mortality for years 1985-2013. The time trends were characterized in terms of an average annual percent change estimated by the log-linear joinpoint regression. The Dyba-Hakulinen method was used for estimation of incidence in 2016 and the projections of cancer incidence for the year 2025 were calculated applying the Globocan projection software. RESULTS: In recent years, near 14,000 Slovenes were diagnosed with cancer per year and just over 6,000 died; more than 94,000 people who were ever diagnosed with cancer are currently living among us. The total burden of cancer is dominated by five most common cancer sites: skin (non-melanoma), colon and rectum, lung, breast and prostate, together representing almost 60% of all new cancer cases. On average the incidence of common cancers in Slovenia is increasing for 3.0% per year in last decade, but the incidence of rare cancers is stable. CONCLUSIONS: Because cancer occurs more among the elderly, and additionally more numerous post-war generation is entering this age group, it is expected that the burden of this disease will be growing further, even if the level of risk factors remains the same as today.