Acceptability of risk-based triage in cervical cancer screening: A focus group study.

BACKGROUND: Compared to the previous cytology-based program, the introduction of primary high-risk human papillomavirus (hrHPV) based screening in 2017 has led to an increased number of referrals. To counter this, triage of hrHPV-positive women in cervical cancer screening can potentially be optimized by taking sociodemographic and lifestyle risk factors for cervical abnormalities into account. Therefore, it is essential to gain knowledge of the views of women (30-60 years) eligible for cervical cancer screening. OBJECTIVE: The main goal of this qualitative study was to gain insight in the aspects that influence acceptability of risk-based triage in cervical cancer screening. DESIGN: A focus group study in which participants were recruited via four general medical practices, and purposive sampling was used to maximize heterogeneity with regards to age, education level, and cervical cancer screening experiences. APPROACH: The focus group discussions were transcribed verbatim and analyzed using reflexive thematic analysis. PARTICIPANTS: A total of 28 women (average age: 45.2 years) eligible for cervical cancer screening in The Netherlands participated in seven online focus group discussions. Half of the participants was higher educated, and the participants differed in previous cervical cancer screening participation and screening result. KEY RESULTS: In total, 5 main themes and 17 subthemes were identified that determine the acceptability of risk-stratified triage. The main themes are: 1) adequacy of the screening program: an evidence-based program that is able to minimize cancer incidence and reduce unnecessary referrals; 2) personal information (e.g., sensitive topics and stigma); 3) emotional impact: fear and reassurance; 4) communication (e.g., transparency); and 5) autonomy (e.g., prevention). CONCLUSION: The current study highlights several challenges regarding the development and implementation of risk-based triage that need attention in order to be accepted by the target group. These challenges include dealing with sensitive topics and a transparent communication strategy.

The dilemma of recalling well-circumscribed masses in a screening population: A narrative literature review and exploration of Dutch screening practice.

BACKGROUND: In Dutch breast cancer screening, solitary, new or growing well-circumscribed masses should be recalled for further assessment. This results in cancers detected but also in false positive recalls, especially at initial screening. The aim of this study was to determine characteristics of well-circumscribed masses at mammography and identify potential methods to improve the recall strategy. METHODS: A systematic literature search was performed using PubMed. In addition, follow-up data were retrieved on all 8860 recalled women in a Dutch screening region from 2014 to 2019. RESULTS: Based on 15 articles identified in the literature search, we found that probably benign well-circumscribed masses that were kept under surveillance had a positive predictive value (PPV) of 0-2%. New or enlarging solitary well-circumscribed masses had a PPV of 10-12%. In general the detected carcinomas had a favorable prognosis. In our exploration of screening practice, 25% of recalls (2133/8860) were triggered by a well-circumscribed mass. Those recalls had a PPV of 2.0% for initial and 10.6% for subsequent screening. Most detected carcinomas had a favorable prognosis as well. CONCLUSION: To recognize malignancies presenting as well-circumscribed masses, identifying solitary, new or growing lesions is key. This information is missing at initial screening since prior examinations are not available, leading to a low PPV. Access to prior clinical examinations may therefore improve this PPV. In addition, given the generally favorable prognosis of screen-detected malignant well-circumscribed masses, one may opt to recall these lesions at subsequent screening, if grown, rather than at initial screening.

Evaluation of reader performance during interpretation of breast cancer screening: the Recall and detection Of breast Cancer in Screening (ROCS) trial study design.

The magnitude of the tradeoff between recall rate (RR) and cancer detection rate (CDR) in breast-cancer screening is not clear, and it is expected to depend on target population and screening program characteristics. Multi-reader multi-case research studies, which may be used to estimate this tradeoff, rely on enriched datasets with artificially high prevalence rates, which may bias the results. Furthermore, readers participating in research studies are subject to "laboratory" effects, which can alter their performance relative to actual practice. The Recall and detection Of breast Cancer in Screening (ROCS) trial uses a novel data acquisition system that minimizes these limitations while obtaining an estimate of the RR-CDR curve during actual practice in the Dutch National Breast Cancer Screening Program. ROCS involves collection of at least 40,000 probability-of-malignancy ratings from at least 20 radiologists during interpretation of approximately 2,000 digital mammography screening cases each. With the use of custom-built software on a tablet, and a webcam, this data was obtained in the usual reading environment with minimal workflow disruption and without electronic access to the review workstation software. Comparison of the results to short- and medium-term follow-up allows for estimation of the RR-CDR and receiver operating characteristics curves, respectively. The anticipated result of the study is that performance-based evidence from practice will be available to determine the optimal operating point for breast-cancer screening. In addition, this data will be useful as a benchmark when evaluating the impact of potential new screening technologies, such as digital breast tomosynthesis or artificial intelligence. KEY POINTS: • The ROCS trial aims to estimate the recall rate-cancer detection rate curve during actual screening practice in the Dutch National Breast Cancer Screening Program. • The study design is aimed at avoiding the influence of the "laboratory effect" in usual observer performance studies. • The use of a tablet and a webcam allows for the acquisition of probability of malignancy ratings without access to the review workstation software.

Women's health behaviour change after receiving breast cancer risk estimates with tailored screening and prevention recommendations.

BACKGROUND: The Predicting Risk of Cancer at Screening (PROCAS) study provided women who were eligible for breast cancer screening in Greater Manchester (United Kingdom) with their 10-year risk of breast cancer, i.e., low (≤1.5%), average (1.5-4.99%), moderate (5.-7.99%) or high (≥8%). The aim of this study is to explore which factors were associated with women's uptake of screening and prevention recommendations. Additionally, we evaluated women's organisational preferences regarding tailored screening. METHODS: A total of 325 women with a self-reported low (n = 60), average (n = 125), moderate (n = 80), or high (n = 60) risk completed a two-part web-based survey. The first part contained questions about personal characteristics. For the second part women were asked about uptake of early detection and preventive behaviours after breast cancer risk communication. Additional questions were posed to explore preferences regarding the organisation of risk-stratified screening and prevention. We performed exploratory univariable and multivariable regression analyses to assess which factors were associated with uptake of primary and secondary breast cancer preventive behaviours, stratified by breast cancer risk. Organisational preferences are presented using descriptive statistics. RESULTS: Self-reported breast cancer risk predicted uptake of (a) supplemental screening and breast self-examination, (b) risk-reducing medication and (c) preventive lifestyle behaviours. Further predictors were (a) having a first degree relative with breast cancer, (b) higher age, and (c) higher body mass index (BMI). Women's organisational preferences for tailored screening emphasised a desire for more intensive screening for women at increased risk by further shortening the screening interval and moving the starting age forward. CONCLUSIONS: Breast cancer risk communication predicts the uptake of key tailored primary and secondary preventive behaviours. Effective communication of breast cancer risk information is essential to optimise the population-wide impact of tailored screening.

Added Value of Prereading Screening Mammograms for Breast Cancer by Radiologic Technologists on Early Screening Outcomes.

Background In the Dutch breast cancer screening program, mammograms are preread by technologists to identify possible abnormalities, leading to "warning signals" (an audible and visual alert if the technologist observed an abnormality suspicious for cancer) for radiologists. The best moment to present these warning signals is unknown. Purpose To determine the effect that blinding of technologists' warning signals has on radiologists' early screening outcome measures during interpretation of mammograms. Materials and Methods In this prospective study from September 2017 to May 2019, on alternating months, radiologists were either blinded or nonblinded to the warning signals of the technologist when interpreting screening mammograms for breast cancer. All discrepancies between radiologists and technologists were reviewed during quality assurance sessions every 6 weeks, which could result in secondary recalls. The outcome measures of this study were recall rate, cancer detection rate, and positive predictive value of recall. A χ2 test was used to test for differences between the two groups. Results During the study period, 109 596 women (mean age, 62 years ± 7 [standard deviation]), including 53 291 in the blinded and 56 305 in the nonblinded groups, participated. The overall recall rate (including secondary recalls) was lower for women in the blinded group than in the nonblinded group (blinded: 1140 of 53 291 women [2.1%], nonblinded: 1372 of 56 305 women [2.4%]; P = .001). There was no evidence of cancer detection rate differences between the groups (blinded: 349 of 53 291 women [6.5 per 1000 screening examinations], nonblinded: 360 of 56 305 women [6.4 per 1000 screening examinations]; P = .75). The blinded group thus had a higher positive predictive value of recall (blinded: 349 of 1140 women [30.6%], nonblinded: 360 of 1372 women [26.2%]; P = .02). Conclusion While interpreting screening mammograms for breast cancer, radiologists blinded to technologists' warning signals had lower recall rates with higher positive predictive values than nonblinded radiologists, yet cancer detection rates seemed to remain unchanged. See also the editorial by Hofvind and Lee in this issue. © RSNA, 2021.

Dutch women's intended participation in a risk-based breast cancer screening and prevention programme: a survey study identifying preferences, facilitators and barriers.

BACKGROUND: Risk-based breast cancer screening may improve the benefit-harm ratio of screening by tailoring policy to a woman's personal breast cancer risk. This study aims to explore Dutch women's preferences regarding the organisation and implementation of a risk-based breast cancer screening and prevention programme, identifying potential barriers and facilitators to uptake. METHODS: A total of 5110 participants in the Dutch Personalised RISk-based MAmmography screening (PRISMA) study were invited, of whom 942 completed a two-part web-based survey. The first part contained questions about personal characteristics; for the second part, women were randomly assigned to one of four hypothetical breast cancer risk scenarios (i.e. low, average, moderate, or high) with subsequent tailored screening and prevention advice. Descriptive statistics are used to present women's organisational preferences. Univariable and multivariable logistic regression analyses were performed using seven proxy measures for acceptability of risk-based screening (e.g., interest in risk) and risk-based prevention (e.g., willingness to change diet). RESULTS: Interest in breast cancer risk was high (80.3%). Higher assigned risk scenario was most consistently associated with acceptance of tailored screening and prevention recommendations. Increased acceptance of lifestyle changes was additionally associated with higher education. Having a first degree family history of breast cancer decreased women's motivation to participate in preventative lifestyle measures. Acceptability of medication was associated with a woman's general beliefs about the (over)use and benefit-harm balance of medication. CONCLUSIONS: Dutch women generally appear in favour of receiving their breast cancer risk estimate with subsequent tailored screening and prevention recommendations. However, women's level of acceptance depends on their assigned risk category. Offering tailored screening and prevention recommendations to low-risk women will be most challenging. Educating women on the benefits and harms of all risk-based screening and prevention strategies is key to acceptability and informed decision-making.

European women's perceptions of the implementation and organisation of risk-based breast cancer screening and prevention: a qualitative study.

BACKGROUND: Increased knowledge of breast cancer risk factors has meant that we are currently exploring risk-based screening, i.e. determining screening strategies based on women's varying levels of risk. This also enables risk management through primary prevention strategies, e.g. a lifestyle programme or risk-reducing medication. However, future implementation of risk-based screening and prevention will warrant significant changes in current practice and policy. The present study explores women's perceptions of the implementation and organisation of risk-based breast cancer screening and prevention to optimise acceptability and uptake. METHODS: A total of 143 women eligible for breast cancer screening in the Netherlands, the United Kingdom, and Sweden participated in focus group discussions. The focus group discussions were transcribed verbatim and the qualitative data was analysed using thematic analysis. RESULTS: Women from all three countries generally agreed on the overall proceedings, e.g. a risk assessment after which the risk estimate is communicated via letter (for below average and average risk) or consultation (for moderate and high risk). However, discrepancies in information needs, preferred risk communication format and risk counselling professional were identified between countries. Additionally, a need to educate healthcare professionals on all aspects of the risk-based screening and prevention programme was established. CONCLUSION: Women's insights identified the need for country-specific standardised protocols regarding the assessment and communication of risk, and the provision of heterogeneous screening and prevention recommendations, monitoring the principle of solidarity in healthcare policy.

The impact of alcohol consumption and physical activity on breast cancer: The role of breast cancer risk.

High alcohol consumption and physical inactivity are known breast cancer risk factors. However, whether the association between these lifestyle factors and breast cancer is modified by a woman's additional breast cancer risk factors has never been studied. Therefore, a population-based prospective cohort study of 57,654 Swedish women aged 40-74 years, including 957 breast cancer cases, was performed. Alcohol consumption and physical activity were measured with validated web-based self-report questionnaires. The Tyrer-Cuzick risk prediction model was used to determine a woman's 10-year risk of developing breast cancer. Logistic regression models were used to explore whether the effect of alcohol consumption and physical activity on breast cancer was modified by additional breast cancer risk factors. Findings showed that increased alcohol consumption was associated with a higher breast cancer risk (OR = 1.26, 95% CI 1.01, 1.59). However, the association between lifestyle factors (alcohol consumption and physical activity) and breast cancer was generally the same for women at below average, average and above average risk of developing breast cancer. Therefore, additional breast cancer risk factors do not appear to modify the association between lifestyle (alcohol consumption and physical activity) and breast cancer. Considering the general health benefits, preventative lifestyle recommendations can be formulated about alcohol consumption and physical activity for women at all levels of breast cancer risk.

Risk prediction of cervical abnormalities: The value of sociodemographic and lifestyle factors in addition to HPV status.

High-risk human papillomavirus (hrHPV) assessment as a primary screening test improves sensitivity but decreases specificity. Determining risk for cervical abnormalities and adapting policy accordingly may improve the balance between screening benefits and harms. Our aim is to assess the value of factors other than HPV in prediction of cervical abnormalities. Data from a Dutch prospective cohort were used. Women aged 18-29 years, not yet eligible for screening, were included in 2007. Data collection consisted of a questionnaire and a cervicovaginal self-sample. Linkage with PALGA (pathology database) was performed in 2017. The analyses included 1483 women. The full model, including sociodemographic and lifestyle factors, was compared to the null model, including baseline HPV only. The outcome of interest was cervical intraepithelial neoplasia 2 or worse (CIN2+). There were 86 women with CIN2+. Baseline hrHPV status was an important predictor (OR = 5.20, 95%CI = 3.27-8.27). The area under the ROC curve (AUC) of the null model was 0.67 (95%CI = 0.61-0.72). The full model had a slightly higher AUC of 0.73 (95%CI = 0.67-0.79). Bootstrap validation indicated that overfitting was present. This exploratory study has confirmed that a single hrHPV measurement is a strong predictor of cervical abnormalities, and additional risk factors in young women appeared to have limited added value. However, prediction based on hrHPV only does leave room for improvement. Future studies should therefore focus on women in the screening age range and search for other predictors to further enhance risk prediction. Adapting policy based on risk may eventually help optimise screening performance.

Utility of Supplemental Training to Improve Radiologist Performance in Breast Cancer Screening: A Literature Review.

PURPOSE: The authors evaluate whether supplemental training for radiologists improves their breast screening performance and how this is measured. METHODS: A systematic search was conducted in PubMed on August 3, 2017. Articles were included if they described supplemental training for radiologists reading mammograms to improve their breast screening performance and at least one outcome measure was reported. Study quality was assessed using the Medical Education Research Study Quality Instrument. RESULTS: Of 2,199 identified articles, 18 were included, of which 17 showed improvement on at least one of the outcome measures, for at least one training activity or subgroup. Two measurement approaches were found. For the first approach, measuring performance on test sets, sensitivity, and specificity were the most reported outcomes (8 of 11 studies). Recall rate is the most reported outcome (6 of 7 studies) for the second approach, which measures performance in actual screening practice. The studies were mainly of moderate quality (Medical Education Research Study Quality Instrument score 11.7 ± 1.7), caused by small sample sizes and the lack of a control group. CONCLUSIONS: Supplemental training helps radiologists improve their screening performance, despite the mainly moderate quality of the studies. There is a need for better designed studies. Future studies should focus on performance in actual screening practice and should look for methods to isolate the training effect. If test sets are used, focus should be on knowledge about correlation between performance on test sets and actual screening practice.

Women's perceptions of personalized risk-based breast cancer screening and prevention: An international focus group study.

OBJECTIVE: Increased knowledge of breast cancer risk factors enables a shift from one-size-fits-all breast cancer screening to a risk-based approach, tailoring screening policy to a woman's individual risk. New opportunities for prevention will arise. However, before this novel screening and prevention program is introduced, its acceptability from a woman's perspective needs to be explored. METHODS: Women eligible for breast cancer screening in the Netherlands, United Kingdom, and Sweden were invited to take part in focus groups. A total of 143 women participated. Data were transcribed verbatim and analyzed using thematic analysis. RESULTS: Analysis identified five themes across the three countries. The first theme "impact of knowledge" describes women's concern of not being able to unlearn their risk, perceiving it as either a motivator for change or a burden which may lead to stigma. The second theme "belief in science" explains women's need to trust the science behind the risk assessment and subsequent care pathways. Theme three "emotional impact" explores, eg, women's perceived anxiety and (false) reassurance, which may result from knowing their risk. Theme four "decision making" highlights cultural differences in shared versus individual decision making. Theme five "attitude to medication" explores the controversial topic of offering preventative medication for breast cancer risk reduction. CONCLUSIONS: Acceptability of risk-based screening and prevention is mixed. Women's perceptions are informed by a lack of knowledge, cultural norms, and common emotional concerns, which highlights the importance of tailored educational materials and risk counselling to aid either shared or individual informed decision making.

Women's decision-making regarding risk-stratified breast cancer screening and prevention from the perspective of international healthcare professionals.

INTRODUCTION: Increased knowledge of breast cancer risk factors may enable a paradigm shift from one-size-fits-all breast cancer screening to screening and subsequent prevention guided by a woman's individual risk of breast cancer. Professionals will play a key role in informing women about this new personalised screening and prevention programme. Therefore, it is essential to explore professionals' views of the acceptability of this new programme, since this may affect shared decision-making. METHODS: Professionals from three European countries (the Netherlands, United Kingdom, and Sweden) participated in digital concept mapping, a systematic mixed methods approach used to explore complex multidimensional constructs. RESULTS: Across the three countries, professionals prioritised the following five themes which may impact decision-making from the perspective of eligible women: (1) Anxiety/worry; (2) Proactive approach; (3) Reassurance; (4) Lack of knowledge; and (5) Organisation of risk assessment and feedback. Furthermore, Dutch and British professionals expressed concerns regarding the acceptability of a heterogeneous screening policy, suggesting women will question their risk feedback and assigned pathway of care. Swedish professionals emphasised the potential impact of the programme on family relations. CONCLUSIONS: The perspectives of Dutch, British, and Swedish professionals of women's decision-making regarding personalised breast cancer screening and prevention generally appear in line with women's own views of acceptability as previously reported. This will facilitate shared decision-making. However, concerns regarding potential consequences of this new programme for screening outcomes and organisation need to be addressed, since this may affect how professionals communicate the programme to eligible women.

Women's perceptions of the adoption of personalised risk-based breast cancer screening and primary prevention: a systematic review.

INTRODUCTION: Increased knowledge of breast cancer risk factors may enable a paradigm shift from the current age-based mammographic screening programmes to a personalised risk-based approach. This would warrant a significant change in practice, yet the acceptability from a woman's perspective has never been systematically explored. In this systematic review, we inventoried and appraised studies of women's perceptions of risk-based breast cancer screening and prevention to identify factors associated with adopting this new paradigm. METHODS: We searched Medline, Embase and PsycInfo to identify original articles in English containing perceptions of risk-based breast cancer screening and/or primary prevention of women with an average to above average risk of developing breast cancer. Qualitative data were systematically extracted and referenced against four theoretical models of preventative health behaviour adoption. RESULTS: When considering the adoption of this novel screening and prevention programme, women carefully review their perceived susceptibility to breast cancer. Their decisions are based on a cost-benefit analysis of adopting lifestyle changes, chemoprevention, or prophylactic surgery, taking into account their perceived competence, individual autonomy, relatedness to others, and personal preference. The role of intent is limited when considering behavioural change. CONCLUSIONS: Implementing risk-based breast cancer screening and prevention will require a multifactorial approach. The transition from theory to practice can be supported by developing evidence-based shared decision aids and family-oriented (genetic) counselling programmes.

Breast density and breast cancer-specific survival by detection mode.

BACKGROUND: Breast density is known to affect breast cancer risk and screening sensitivity, but it may also be associated with breast cancer survival. The interpretation of results from previous studies on breast density and survival is complicated by the association between detection mode and survival. Here, we studied the effect of breast density on breast cancer-specific survival for different detection modes (screen-detected, interval ≤ 24 or > 24 months, non-participant). METHODS: Data from the Nijmegen (Dutch) breast cancer screening programme were used. Women diagnosed with invasive breast cancer between 1975 and 2011 were included. Breast density was assessed visually, based on a dichotomized Wolfe scale: 'fatty breasts' (≤25%) and 'dense breasts' (> 25%). Cox proportional hazard regression was used to obtain hazard ratios (HR). RESULTS: We identified 2742 eligible women, with a breast pattern available for 2233 women. A diagnosis of interval cancer (HR 2.06, 95% CI 1.62-2.61) led to a significantly increased risk of breast cancer death compared with screen-detected cancer. No significant cause-specific survival difference between women with dense and fatty breasts was observed (HR 0.94, 95% CI 0.77-1.15). The hazard was only higher for women with dense breasts among interval cancers ≤24 m (HR 1.07, 95% CI 0.74-1.56). The hazard appeared to be lower for women with dense breasts than for women with fatty breasts among screen-detected (HR 0.77, 95% CI 0.53-1.11) and interval cancers > 24 m (HR 0.80, 95% CI 0.53-1.20). None of the effects were statistically significant. CONCLUSIONS: Detection mode is strongly associated with breast cancer death. No clear association is apparent between breast density and breast cancer death, regardless of detection mode.

Are we ready for the challenge of implementing risk-based breast cancer screening and primary prevention?

BACKGROUND: Increased knowledge of breast cancer risk factors provides opportunities to shift from a one-size-fits-all screening programme to a personalised approach, where screening and prevention is based on a woman's risk of developing breast cancer. However, potential implementation of this new paradigm could present considerable challenges which the present review aims to explore. METHODS: Bibliographic databases were searched to identify studies evaluating potential implications of the implementation of personalised risk-based screening and primary prevention for breast cancer. Identified themes were evaluated using thematic analysis. RESULTS: The search strategy identified 5699 unique publications, of which 59 were selected for inclusion. Significant changes in policy and practice are warranted. The organisation of breast cancer screening spans several healthcare delivery systems and clinical settings. Feasibility of implementation depends on how healthcare is funded and arranged, and potentially varies between countries. Piloting risk assessment and prevention counselling in primary care settings has highlighted implications relating to the need for extensive additional training on risk (communication) and prevention, impact on workflow, and professionals' personal discomfort breaching the topic with women. Additionally, gaps in risk estimation, psychological, ethical and legal consequences will need to be addressed. CONCLUSION: The present review identified considerable unresolved issues and challenges. Potential implementation will require a more complex framework, in which a country's healthcare regulations, resources, and preferences related to screening and prevention services are taken into account. However, with the insights gained from the present overview, countries expecting to implement risk-based screening and prevention can start to inventory and address the issues that were identified.

Breast cancer screening effect across breast density strata: A case-control study.

Breast cancer screening is known to reduce breast cancer mortality. A high breast density may affect this reduction. We assessed the effect of screening on breast cancer mortality in women with dense and fatty breasts separately. Analyses were performed within the Nijmegen (Dutch) screening programme (1975-2008), which invites women (aged 50-74 years) biennially. Performance measures were determined. Furthermore, a case-control study was performed for women having dense and women having fatty breasts. Breast density was assessed visually with a dichotomized Wolfe scale. Breast density data were available for cases. The prevalence of dense breasts among controls was estimated with age-specific rates from the general population. Sensitivity analyses were performed on these estimates. Screening performance was better in the fatty than in the dense group (sensitivity 75.7% vs 57.8%). The mortality reduction appeared to be smaller for women with dense breasts, with an odds ratio (OR) of 0.87 (95% CI 0.52-1.45) in the dense and 0.59 (95% CI 0.44-0.79) in the fatty group. We can conclude that high density results in lower screening performance and appears to be associated with a smaller mortality reduction. Breast density is thus a likely candidate for risk-stratified screening. More research is needed on the association between density and screening harms.

The relative effect of mammographic screening on breast cancer mortality by socioeconomic status.

Breast cancer incidence and mortality are higher in women with a high socioeconomic status (SES). The potential to prevent death from breast cancer is therefore greater in the high SES group. This does, however, require that the effectiveness of screening in the high SES group is equal to or greater than the effectiveness in the low SES group. The aim of this study is to assess the relative effectiveness of mammographic screening on breast cancer mortality by SES.In Nijmegen, the Netherlands, women are invited to participate in biennial mammographic screening since 1975. Postal code is collected at each round and is used to calculate the SES of each woman based on the SES indicator of the Netherlands Institute for Social Research. The Dutch average was used to classify the SES score of each woman as either high or low. We designed a case-control study to investigate the effect of mammographic screening in women aged 50 to 75, 40 to 75, and 50 to 69 years, and calculated the odds ratios (ORs) and 95% confidence intervals (CIs).Among the women invited to the mammographic screening program in Nijmegen, 10% had a high SES. In women aged 50 to 75 years, the breast cancer death rate was 38% lower in screened women than in unscreened women. The ORs for women with high SES (OR 0.82, 95% CI 0.31-2.19) and low SES did not differ significantly (OR 0.61, 95% CI 0.47-0.78).Mammographic screening reduces breast cancer mortality, but we did not observe a significant difference in the relative effectiveness of screening by SES. If the effectiveness of mammographic screening is indeed not dependent on SES status, the absolute number of breast cancer deaths prevented by mammographic screening will be greater in the high SES than low SES group, because women with a high SES have a greater risk of breast cancer death.

Comparing Visually Assessed BI-RADS Breast Density and Automated Volumetric Breast Density Software: A Cross-Sectional Study in a Breast Cancer Screening Setting.

INTRODUCTION: The objective of this study is to compare different methods for measuring breast density, both visual assessments and automated volumetric density, in a breast cancer screening setting. These measures could potentially be implemented in future screening programmes, in the context of personalised screening or screening evaluation. MATERIALS AND METHODS: Digital mammographic exams (N = 992) of women participating in the Dutch breast cancer screening programme (age 50-75y) in 2013 were included. Breast density was measured in three different ways: BI-RADS density (5th edition) and with two commercially available automated software programs (Quantra and Volpara volumetric density). BI-RADS density (ordinal scale) was assessed by three radiologists. Quantra (v1.3) and Volpara (v1.5.0) provide continuous estimates. Different comparison methods were used, including Bland-Altman plots and correlation coefficients (e.g., intraclass correlation coefficient [ICC]). RESULTS: Based on the BI-RADS classification, 40.8% of the women had 'heterogeneously or extremely dense' breasts. The median volumetric percent density was 12.1% (IQR: 9.6-16.5) for Quantra, which was higher than the Volpara estimate (median 6.6%, IQR: 4.4-10.9). The mean difference between Quantra and Volpara was 5.19% (95% CI: 5.04-5.34) (ICC: 0.64). There was a clear increase in volumetric percent dense volume as BI-RADS density increased. The highest accuracy for predicting the presence of BI-RADS c+d (heterogeneously or extremely dense) was observed with a cut-off value of 8.0% for Volpara and 13.8% for Quantra. CONCLUSION: Although there was no perfect agreement, there appeared to be a strong association between all three measures. Both volumetric density measures seem to be usable in breast cancer screening programmes, provided that the required data flow can be realized.

Geographic variation in volumetric breast density between screening regions in the Netherlands.

OBJECTIVES: Differences in breast density between populations may explain part of the variation in regional breast cancer screening performance. This study aimed to determine whether regional differences in breast density distribution are present in the Dutch screening population. METHODS: As part of the DENSE trial, mammographic density was measured using a fully-automated volumetric method. The regions in our study were based on the geographic coverage of 14 reading units representing a large part of the Netherlands. General linear models were used. RESULTS: Four hundred eighty-five thousand and twenty-one screening participants with a median age of 60 years were included (2013-2014). The proportion of women with heterogeneously or extremely dense breasts ranged from 32.5% to 45.7% between regions. Mean percent dense volume varied between 6.51% (95% confidence interval [CI]: 6.46-6.55) and 7.68% (95% CI: 7.66-7.71). Age differences could not explain the variation. Socio-economic status (SES) was positively associated with volumetric density in all analyses (low SES: 6.95% vs. high SES: 7.63%; p trend < 0.0001), whereas a potential association between urbanisation and breast density only became apparent after SES adjustment. CONCLUSION: There appears to be geographic variation in mammographic density in the Netherlands, emphasizing the importance of including breast density as parameter in the evaluation of screening performance. KEY POINTS: • Mammographic density may affect regional breast cancer screening performance. • Volumetric breast density varies across screening areas. • SES is positively associated with breast density. • Implications of volumetric breast density differences need to be studied further.

Case-control Studies on the Effectiveness of Breast Cancer Screening: Insights from the UK Age Trial.

BACKGROUND: Ongoing breast cancer screening programs can only be evaluated using observational study designs. Most studies have observed a reduction in breast cancer mortality, but design differences appear to have resulted in different estimates. Direct comparison of case-control and trial analyses gives more insight into this variation. Here, we performed case-control analyses within the randomized UK Age Trial. METHODS: The Age Trial assessed the effect of screening on breast cancer mortality in women ages 40-49 years. In our approach, case subjects were defined as breast cancer deaths between trial entry (1991-1997) and 2004. Women were ages 39-41 years at entry. For every case subject, five control subjects were selected. All case subjects were included in analyses of screening invitation (356 case subjects, 1,780 controls), whereas analyses of attendance were restricted to women invited to screening (105 case subjects, 525 age-matched controls). Odds ratios (OR) were estimated with conditional logistic regression. We used and compared two methods to correct for self-selection bias. RESULTS: Screening invitation resulted in a breast cancer mortality reduction of 17% (95% confidence interval [CI]: -36%, +6%), similar to trial results. Different exposure definitions and self-selection adjustments influenced the observed breast cancer mortality reduction. Depending on the method, "ever screened" appeared to be associated with a small reduction (OR: 0.86, 95% CI: 0.40, 1.89) or no reduction (OR: 1.02, 95% CI: 0.48, 2.14) using the two methods of correction. Recent attendance resulted in an adjusted mortality reduction of 36% (95% CI: -69%, +31%) or 45% (95% CI: -71%, +5%). CONCLUSIONS: Observational studies, and particularly case-control studies, are an important monitoring tool for breast cancer screening programs. The focus should be on diminishing bias in observational studies and gaining a better understanding of the influence of study design on estimates of mortality reduction.