Search

Objectives: Insight into the aggressiveness of potential breast cancers found in screening may optimize recall decisions. Specific growth rate (SGR), measured on mammograms, may provide valuable prognostic information. This study addresses the association of SGR with prognostic factors and overall survival in patients with invasive carcinoma of no special type (NST) from a screened population. Methods: In this historic cohort study, 293 women with NST were identified from all participants in the Nijmegen screening program (2003–2007). Information on clinicopathological factors was retrieved from patient files and follow-up on vital status through municipalities. On consecutive mammograms, tumor volumes were estimated. After comparing five growth functions, SGR was calculated using the best-fitting function. Regression and multivariable survival analyses described associations between SGR and prognostic factors as well as overall survival. Results: Each one standard deviation increase in SGR was associated with an increase in the Nottingham prognostic index by 0.34 [95% confidence interval (CI): 0.21–0.46]. Each one standard deviation increase in SGR increased the odds of a tumor with an unfavorable subtype (based on histologic grade and hormone receptors; odds ratio 2.14 [95% CI: 1.45–3.15]) and increased the odds of diagnosis as an interval cancer (versus screen-detected; odds ratio 1.57 [95% CI: 1.20–2.06]). After a median of 12.4 years of follow-up, 78 deaths occurred. SGR was not associated with overall survival (hazard ratio 1.12 [95% CI: 0.87–1.43]). Conclusions: SGR may indicate prognostically relevant differences in tumor aggressiveness if serial mammograms are available. A potential association with cause-specific survival could not be determined and is of interest for future research. [ABSTRACT FROM AUTHOR]

A false positive (FP) referral after screening mammography may influence a woman's likelihood to re-attend the screening program. The impact of having a FP result in the first or subsequent screening round on re-attendance after a FP result was investigated. In addition, we aimed to study differences in re-attendance rates between women who underwent non-invasive and invasive additional examinations as part of the diagnostic work-up following a FP referral. A consecutive series of 13,597 women with a FP referral following biennial screening mammography in the south of the Netherlands between 2009 and 2019 was included. The screening re-attendance rate was 81.2% after a FP referral, and 91.3% when also including women who had clinical mammographic follow-up. Women who received a FP referral in the first screening round were less likely to re-attend the screening programme in the following three years, compared to those with a FP test in any subsequent round (odds ratio (OR): 0.59, 95%-confidence interval (CI): 0.51–0.69). Women with a FP referral who underwent invasive examinations after referral were less likely to re-attend the screening programme than those who only received additional imaging (OR, 0.48; 95% CI 0.36–0.64). Women with a FP referral are less likely to re-attend the screening programme if this referral occurs at their first screening round or when they undergo invasive diagnostic workup. Hospitals and screening organizations should prioritize informing women about the importance of re-attending the programme following a FP referral. • Of all screened women more than 70% experience a false positive (FP) referral. • The screening re-attendance rate after a FP referral was 81.2%. • An additional 10.1% underwent clinical mammographic follow-up instead. • Women with a FP referral in the first screening round were less likely to re-attend. • Women should be encouraged to attend regular screening following a FP referral. [ABSTRACT FROM AUTHOR]

Purpose: Follow-up guidelines barely diverge from a one-size-fits-all approach, even though the risk of recurrence differs per patient. However, the personalization of breast cancer care improves outcomes for patients. This study explores the variation in follow-up pathways in the Netherlands using real-world data to determine guideline adherence and the gap between daily practice and risk-based surveillance, to demonstrate the benefits of personalized risk-based surveillance compared with usual care., Methods: Patients with stage I-III invasive breast cancer who received surgical treatment in a general hospital between 2005 and 2020 were selected from the Netherlands Cancer Registry and included all imaging activities during follow-up from hospital-based electronic health records. Process analysis techniques were used to map patients and activities to investigate the real-world utilisation of resources and identify the opportunities for improvement. The INFLUENCE 2.0 nomogram was used for risk prediction of recurrence., Results: In the period between 2005 and 2020, 3478 patients were included with a mean follow-up of 4.9 years. In the first 12 months following treatment, patients visited the hospital between 1 and 5 times (mean 1.3, IQR 1-1) and received between 1 and 9 imaging activities (mean 1.7, IQR 1-2). Mammogram was the prevailing imaging modality, accounting for 70% of imaging activities. Patients with a low predicted risk of recurrence visited the hospital more often., Conclusions: Deviations from the guideline were not in line with the risk of recurrence and revealed a large gap, indicating that it is hard for clinicians to accurately estimate this risk and therefore objective risk predictions could bridge this gap., (© 2024. The Author(s).)

Background: No studies are available in which changes over time in characteristics and prognosis of patients with interval breast cancers (ICs) and screen-detected breast cancers (SDCs) have been compared. The aim was to study these trends between 1995 and 2018., Methods: All women with invasive SDCs (N = 4290) and ICs (N = 1352), diagnosed in a southern mammography screening region in the Netherlands, were included and followed until date of death or 31 December 2022., Results: The 5-year overall survival rate of women with SDCs increased from 91.4% for those diagnosed in 1995-1999 to 95.0% for those diagnosed in 2013-2018 (P < 0.001), and from 74.8 to 91.6% (P < 0.001) in the same periods for those with ICs. A similar trend was observed for the 10-year survival rates. After adjustment for changes in tumour characteristics, the hazard ratio (HR) for overall survival was 0.47 (95% confidence interval (CI): 0.38-0.59) for women with SDCs diagnosed in the period 2013-2018, compared to the women diagnosed in the period 1995-1999. For the women with ICs this HR was 0.27 (95% CI: 0.19-0.40)., Conclusion: The prognosis of women with ICs has improved rapidly since 1995 and is now almost similar to that of women with SDCs., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Objective: Decision-making about breast cancer screening requires balanced and understandable information that takes prior beliefs of screening invitees into account., Methods: In qualitative interviews with 22 Dutch women who were invited for screening for the first time (49-52 years of age, varying health literacy levels), we gained insight in their beliefs on breast cancer and breast cancer screening, and explored how the current screening information matched these beliefs., Results: Breast cancer was perceived as an unpredictable, severe, and uncontrollable disease. Women considered screening as self-evident and an important mean to gain some control over breast cancer. Information on benefits of screening was in line with women's prior beliefs and confirmed women's main reasons to participate. Information about false-positive outcomes, overtreatment, and false negative outcomes did not correspond to women's prior beliefs and this information was generally not considered relevant for decision-making. Preferences for additional information merely concerned practical information on the screening procedure., Conclusion: Complex information on the harms of screening does not match women's beliefs and is not taken into account in their decision-making., Practice Implications: Information regarding breast cancer screening could be further aligned to prior beliefs by taking into account values, filling knowledge gaps and correct misconceptions., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Objectives: We investigated whether changes in mammographic technique and screening policy have improved mammographic sensitivity, and elongated the mean sojourn time, since the introduction of biennial breast cancer screening in Nijmegen, the Netherlands, in 1975. Methods: Maximum likelihood estimation, non-linear regression, and Markov Chain Monte Carlo simulation were used to estimate test sensitivity, mean sojourn time, and underlying breast cancer incidence in four time periods, covering 40 years of breast cancer screening in Nijmegen (1975–2012). Results: Maximum likelihood estimation generated an estimated test sensitivity of approximately 90% and a mean sojourn time around three years, while the estimates based on non-linear regression and Markov Chain Monte Carlo simulation were 80% and four years, respectively. All three methods estimated a rise in the underlying breast cancer incidence over time, with approximately one case more per 1000 women per year in the final period compared with the first period. Conclusions: The three methods showed a slightly higher mammographic sensitivity and a longer mean sojourn time in the last period, after the introduction of digital mammography. Estimates were more realistic for the more sophisticated methods, non-linear regression and Markov Chain Monte Carlo simulation, while the simple closed form approximation of maximum likelihood estimation led to rather high estimates for sensitivity in the early periods. [ABSTRACT FROM AUTHOR]

Objective As breast cancer growth rate is associated with menopause, most screening programmes target mainly women aged 50–74. We studied the association between age at diagnosis and growth rate in this screening-specific age range. Methods We used data from breast cancer patients diagnosed in the screening programme in Nijmegen, the Netherlands. The data were restricted to the screening rounds when analogue mammography was used in both the screening and clinical setting. Growth rate expressed as tumour volume doubling time was based on increasing tumour size in longitudinal series of mammograms. Estimates were based on (a) tumours showing at least two measurable shadows, (b) tumours showing a shadow at detection only (left censored), and (c) tumours showing no growth (right-censored observation). All 293 tumours were consecutively diagnosed invasive ductal breast cancers in participants of the Nijmegen screening programme in the period 2000–2007. Results Depending on the assumptions made on tumour margins and mammographic density, the relation of volume doubling time with age non-significantly varies from a decrease of 3.3% to an increase of 1.4% for each year increase in age at diagnosis (all P-values ≥ 0.18). Applying left censoring on indistinct tumours, the geometric mean volume doubling time was 191 days (95% confidence interval 158–230). Conclusion We found no significant change in growth rate with age in women diagnosed with invasive ductal breast cancer in the screening age range 50–74. This outcome does not support differential screening intervals by age based solely on breast cancer growth rate for this particular group. [ABSTRACT FROM AUTHOR]

Background: Population screening with mammography has resulted in increased detection of ductal carcinoma in situ (DCIS). The aim of this population-based cohort study was to assess whether the method of detection should be considered when determining prognosis and treatment in women with DCIS.Methods: This study includes 7042 women aged 49-75 years, who were surgically treated for primary DCIS between 1989 and 2004 in the Netherlands. We calculated cumulative incidences of ipsilateral and contralateral invasive breast cancer and all-cause mortality among women with screen-detected, interval, or non-screening-related DCIS, and assessed the association between method of detection and these outcomes, using multivariable Cox regression analyses.Results: Compared with non-screening-related DCIS, women with screen-detected DCIS had a lower risk of developing ipsilateral invasive breast cancer (hazard ratio (HR) = 0.75, 95% CI = 0.59-0.96), but a similar risk of contralateral invasive breast cancer (HR = 0.86, 95% CI = 0.67-1.10). The absolute difference in risk of ipsilateral invasive breast cancer was 1% at 15 years. Screen detection was associated with lower all-cause mortality (HR = 0.85, 95% CI = 0.73-0.98); when we additionally accounted for the occurrence of invasive breast cancer the magnitude of this effect remained similar (HR = 0.86, 95% CI = 0.75-1.00).Conclusions: Screen detection was associated with lower risk of ipsilateral invasive breast cancer and all-cause mortality. However, the absolute difference in risk of ipsilateral invasive breast cancer was very low and the lower all-cause mortality associated with screen-detected and interval DCIS might be explained by a healthy-user effect. Therefore, our findings do not justify different treatment strategies for women with screen-detected, interval, or non-screening-related DCIS. [ABSTRACT FROM AUTHOR]

Due to COVID-19, the Dutch breast cancer screening program was interrupted for three months with uncertain long-term effects. The aim of this study was to estimate the long-term impact of this interruption on delay in detection, tumour size of screen-detected breast cancers, and interval cancer rate. After validation, the micro-simulation model SiMRiSc was used to calculate the effects of interruption of the breast cancer screening program for three months and for hypothetical interruptions of six and twelve months. A scenario without interruption was used as reference. Outcomes considered were tumour size of screen-detected breast cancers and interval cancer rate. Women of 55–59 and 60–64 years old at time of interruption were considered. Uncertainties were estimated using a sensitivity analysis. The three-month interruption had no clinically relevant long-term effect on the tumour size of screen-detected breast cancers. A 19% increase in interval cancer rate was found between last screening before and first screening after interruption compared to no interruption. Hypothetical interruptions of six and twelve months resulted in larger increases in interval cancer rate of 38% and 78% between last screening before and first screening after interruption, respectively, and an increase in middle-sized tumours in first screening after interruption of 26% and 47%, respectively. In conclusion, the interruption of the Dutch screening program is not expected to result in a long-term delay in detection or clinically relevant change in tumour size of screen-detected cancers, but only affects the interval cancer rate between last screening before and first screening after interruption. • The Dutch screening interruption causes no delay in breast cancer detection after restart. • No relevant change in screen-detected tumour size is expected. • Interval cancer rate increases before first screening after interruption. • Longer interruption periods are associated with larger effects. [ABSTRACT FROM AUTHOR]

Breast cancer is one of the most common types of cancer among women. National mammography screening programs can detect breast cancer early, but attendance rates have been decreasing in the Netherlands over the past decade. Non-attendees reported that overdiagnosis, the risk of false-negative results, x-ray exposure and mammography pain could be barriers to attendance, but it is not clear whether these disadvantages explain non-attendance and in which situations they are considered barriers. We conducted a national survey among 1227 Dutch women who did not attend mammography screening appointments in 2016. Logistic regression models were used to identify factors that influenced the likelihood of the abovementioned disadvantages leading to non-attendance. The results showed that the doctor's opinion increased the likelihood of the risk of false-negative being perceived as a reason for non-attendance. Moreover, opportunistic screening increased the likelihood that the risk of false-negative, overdiagnosis and x-ray exposure would lead to non-attendance. Women with lower education levels were less likely to consider overdiagnosis and x-ray exposure as reasons for non-attendance, while women who had not undergone mammography screening before were more likely to reject the screening invitation because of concerns about x-ray exposure and mammography pain. These findings indicate how we can address the specific concerns of different groups of women in the Netherlands to encourage them to attend potentially life-saving breast-screening appointments. Screening organizations could provide accurate and unbiased information on the effectiveness of mammography screening to GPs, putting them in a better position to advise their patients., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Purpose: Our purpose was to compare mammographic positioning quality of new (NR) versus experienced screening radiographers (ER) in the Netherlands.Methods and Materials: Before starting to work in breast screening, NR must complete an education programme including a theoretical course (four days), practical training (six weeks), and a portfolio-review of 50 mammographic screening examinations performed by the radiographer. Furthermore, Dutch screening has an extensive system of quality assurance, including an audit-review of positioning quality of mammograms by ER. We analysed 13,520 portfolio views (NR) and 14,896 audit views (ER) based on pre-specified criteria, e.g., depiction of inframammary angle.Results: Overall positioning was more adequate for NR than ER (CC views: 97% versus 86%, p = 0.00; MLO views: 92% versus 84%, p = 0.00). NR scored better for most of the CC-criteria and showed, for instance, less folds (inadequate: 10% versus 16%, p = 0.00). In contrast, NR encountered more difficulties for MLO views in, for example, depiction of infra-mammary angle (inadequate: 38% versus 34%, p = 0.00). Overall, mammograms from NR were more often considered adequate, because of less severe errors.Conclusion: NR perform better than ER in overall positioning technique. These results stress the need for continuous monitoring and training in breast screening programmes to keep positioning skills up to date.Key Points: • We evaluated positioning quality of new and experienced Dutch screening radiographers. • New radiographers outperform their experienced colleagues in mammographic positioning quality. • New radiographers make less severe errors compared to experienced colleagues. • There is a need for a continuous individual monitoring and feedback system. [ABSTRACT FROM AUTHOR]

Objectives: Our aim was to retrospectively evaluate the results of all audits performed in the past and to assess their value in the quality assurance of the Dutch breast cancer screening programme.Methods: The audit team of the Dutch Reference Centre for Screening (LRCB) conducts triennial audits of all 17 reading units. During audits, screening outcomes like recall rates and detection rates are assessed and a radiological review is performed. This study investigates and compares the results of four audit series: 1996-2000, 2001-2005, 2003-2007 and 2010-2013.Results: The analysis shows increased recall rates (from 0.66%, 1.07%, 1.22% to 1.58%), increased detection rates (from 3.3, 4.5, 4.8 to 5.4 per 1000) and increased sensitivity (from 64.5%, 68.7%, 70.5% to 71.6%), over the four audit series. The percentage of 'missed cancers' among interval cancers and advanced screen-detected cancers did not change (p = 0.4).Conclusions: Our audits not only provide an opportunity for assessing screening outcomes, but also provide moments of self-reflection with peers. For radiologists, an accurate understanding of their performance is essential to identify points of improvement. We therefore recommend a radiological review of screening examinations and immediate feedback as part of an audit.Key Points: • Radiological review and immediate feedback are recommended as part of an audit. • For breast screening radiologists, audits provide moments of self-reflection with peers. • Radiological review of screening examinations provides insights in recall behaviour. • Accurate understanding of radiologists' performance is essential to identify points of improvement. [ABSTRACT FROM AUTHOR]

Gynecomastia is the most common abnormality of the male breast. However, breast cancer may occur, albeit with a significantly lower incidence than in females. Imaging is often used as part of the diagnosis. The aim of this study was to assess the utilization and outcome of imaging with mammography or ultrasound of the male breast in a university hospital's department of radiology. A retrospective study assessing the imaging of the male breast in 557 patients over a 10-year period. Referral was done mainly by general surgeons and general practitioners. The most common indication was enlargement of the breast, described as gynecomastia or swelling in 74% of patients, followed by pain in 24% and 'lumps' in 10%. The modalities used were mammography in 65%, ultrasound in 51% and both in 26%. Most examinations, 519, were BI- RADS 1 or 2, and 38 were BI- RADS 3 or higher. Altogether 160 patients had additional fine-needle aspiration or biopsy. Malignancies were diagnosed in five patients (0.89%). Imaging had a sensitivity of 80% and a specificity of 99%. The positive predictive value was 44% and the negative predictive value 99.8%. Malignancies are rare in the male breast. The probability of finding cancer when performing imaging of clinically benign findings in the male breast is negligible. Imaging is not warranted unless there are suspicious abnormalities. Routine imaging of gynecomastia should be discouraged. [ABSTRACT FROM AUTHOR]

Background Women require balanced, high-quality information when making an informed decision on screening benefits and harms before attending biennial mammographic screening. Patients and methods The cumulative risk of a false-positive recall and/or (small) screen-detected or interval cancer over 13 consecutive screening examinations for women aged 50 from the start of screening were estimated using data from the Nijmegen programme, the Netherlands. Results Women who underwent 13 successive screens in the period 1975–1976 had a 5.3% cumulative chance of a screen-detected cancer, with a 4.2% risk of at least one false-positive recall. The risk of being diagnosed with interval cancer was 3.7%. Two decades later, these estimates were 6.9%, 7.3% and 2.9%, respectively. The chance of detection of a small, favourable invasive breast cancer, anticipating a normal life-expectancy, rose from 2.3% to 3.7%. Extrapolation to digital screening mammography indicates that the proportion of false-positive results will rise to 16%. Conclusion Dutch women about to participate in the screening programme can be reassured that the chance of false-positive recall in the Netherlands is relatively low. A new screening policy and improved mammography have increased the detection of an early screening carcinoma and lowering the risk of interval carcinoma. [ABSTRACT FROM PUBLISHER]

Objectives: To determine the influence of local contrast optimisation on diagnostic accuracy and perceived suspiciousness of digital screening mammograms. Methods: Data were collected from a screening region in the Netherlands and consisted of 263 digital screening cases (153 recalled,110 normal). Each case was available twice, once processed with a tissue equalisation (TE) algorithm and once with local contrast optimisation (PV). All cases had digitised previous mammograms. For both algorithms, the probability of malignancy of each finding was scored independently by six screening radiologists. Perceived case suspiciousness was defined as the highest probability of malignancy of all findings of a radiologist within a case. Differences in diagnostic accuracy of the processing algorithms were analysed by comparing the areas under the receiver operating characteristic curves ( A). Differences in perceived case suspiciousness were analysed using sign tests. Results: There was no significant difference in A (TE: 0.909, PV 0.917, P = 0.46). For all radiologists, perceived case suspiciousness using PV was higher than using TE more often than vice versa (ratio: 1.14-2.12). This was significant ( P <0.0083) for four radiologists. Conclusions: Optimisation of local contrast by image processing may increase perceived case suspiciousness, while diagnostic accuracy may remain similar. Key Points: • Variations among different image processing algorithms for digital screening mammography are large. • Current algorithms still aim for optimal local contrast with a low dynamic range. • Although optimisation of contrast may increase sensitivity, diagnostic accuracy is probably unchanged. • Increased local contrast may render both normal and abnormal structures more conspicuous. [ABSTRACT FROM AUTHOR]

Health technology assessment (HTA) was developed in the 1970s and 1980s to facilitate decision making on the desirability of new biomedical technologies. Since then, many of the standard tools and methods of HTA have been criticized for their implicit normativity. At the same time research into the character of technology in practice has motivated philosophers, sociologists and anthropologists to criticize the traditional view of technology as a neutral instrument designed to perform a specific function. Such research suggests that the tools and methods of more traditional forms of HTA are often inspired by an 'instrumentalist' conception of technology that does not fit the way technology actually works. This paper explores this hypothesis for a specific case: the assessments and deliberations leading to the introduction of breast cancer screening in the Netherlands. After reconstructing this history of HTA 'in the making' the stepwise model of HTA that emerged during the process is discussed. This model was rooted indeed in an instrumentalist conception of technology. However, a more detailed reconstruction of several episodes from this history reveals how the actors already experienced the inadequacy of some of the instrumentalist presuppositions. The historical case thus shows how an instrumentalist conception of technology may result in implicit normative effects. The paper concludes that an instrumentalist view of technology is not a good starting point for HTA and briefly suggests how the fit between HTA methods and the actual character of technology in practice might be improved. [ABSTRACT FROM AUTHOR]

Introduction: Exposure to ionizing radiation at mammography screening may cause breast cancer. Because the radiation risk increases with lower exposure age, advancing the lower age limit may affect the balance between screening benefits and risks. The present study explores the benefit-risk ratio of screening before age 50.Methods: The benefits of biennial mammography screening, starting at various ages between 40 and 50, and continuing up to age 74 were examined using micro-simulation. In contrast with previous studies that commonly used excess relative risk models, we assessed the radiation risks using the latest BEIR-VII excess absolute rate exposure-risk model.Results: The estimated radiation risk is lower than previously assessed. At a mean glandular dose of 1.3 mGy per view that was recently measured in the Netherlands, biennial mammography screening between age 50 and 74 was predicted to induce 1.6 breast cancer deaths per 100,000 women aged 0-100 (range 1.3-6.3 extra deaths at a glandular dose of 1-5 mGy per view), against 1121 avoided deaths in this population. Advancing the lower age limit for screening to include women aged 40-74 was predicted to induce 3.7 breast cancer deaths per 100,000 women aged 0-100 (range 2.9-14.4) at biennial screening, but would also prevent 1302 deaths.Conclusion: The benefits of mammography screening between age 40 and 74 were predicted to outweigh the radiation risks. [ABSTRACT FROM AUTHOR]

Background: The United Kingdom is currently moving the age limit for invitation in its national breast screening programme downwards from 50 to 47. In contrast, the US Preventive Services Task Force concluded that, because of borderline statistical significance on effectiveness of mammographic screening, the current evidence is insufficient to advise screening in women aged 40–49. Material and methods: We designed a case-referent study to investigate the effect of biennial mammographic screening on breast cancer mortality for women in their forties. In Nijmegen, the Netherlands, screening started in 1975. A total of 272 breast cancer deaths were identified, and 1360 referents aged 40–69 were sampled from the population invited for screening. Effectiveness was estimated by calculating the odds ratio (OR) indicating the breast cancer death rate in screened versus unscreened women. Results: In women aged 40–49, the effect of screening was OR=0.50 (95% confidence interval (CI)=0.30–0.82). This result is similar to those aged 50–59 (OR=0.54; 95% CI=0.35–0.85) and 60–69 (OR=0.65; 95% CI=0.38–1.13). Conclusion: Our results add convincing evidence about the effectiveness of biennial mammographic screening in women aged 40–49. [Copyright &y& Elsevier]

The article presents a study which compares the life expectancy between women with screen-detected invasive breast cancer and those invited to breast cancer screening program in Nijmegen, Netherlands (comparison group). It states that survival analyses were done to compare life expectancy differences. Results show that life expectancy of screen-detected invasive breast cancer and comparison group are similar while women with larger tumor diagnosis decreases and is modified by screening history.

This paper focuses on the legal implications in terms of duties and responsibilities for radiologists and radiologic technologists of independent pre-reading of mammograms by radiologic technologists, so patients could be discharged without being seen by a radiologist. Pre-reading could be effectuated when preconditions are met to perform reserved procedures by unauthorised professionals as stated in the Individual Health Care Professions (IHCP) Act. Furthermore, compliance with a protocol or code of conduct in combination with adequate training and supervision should be sufficient to disprove potential claims. For a wide implementation, pre-reading should be well-embedded in legal rules and should answer the professional standard of care. [ABSTRACT FROM AUTHOR]

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 χ 2 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.

Purpose: Problem solving magnetic resonance imaging (MRI) is used to exclude malignancy in women with equivocal findings on conventional imaging. However, recommendations on its use for women recalled after screening are lacking. This study evaluates the impact of problem solving MRI on diagnostic workup among women recalled from the Dutch screening program, as well as time trends and inter-hospital variation in its use., Methods: Women who were recalled at screening mammography in the South of the Netherlands (2008-2017) were included. Two-year follow-up data were collected. Diagnostic-workup and accuracy of problem solving MRI were evaluated and time trends and inter-hospital variation in its use were examined., Results: In the study period 16,175 women were recalled, of whom 906 underwent problem solving MRI. Almost half of the women (45.4%) who underwent problem solving MRI were referred back to the screening program without further workup. The sensitivity, specificity, and positive and negative predictive values of problem solving MRI were 98.2%, 70.0%, 31.1%, and 99.6%, respectively. The percentage of recalled women receiving problem solving MRI fluctuated over time (4.7%-7.2%) and significantly varied among hospitals (2.2%-7.0%)., Conclusion: The use of problem solving MRI may exclude malignancy in recalled women. The use of problem solving MRI varied over time and among hospitals, which indicates the need for guidelines on problem solving MRI., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The COVID-19 pandemic forced the Dutch national breast screening program to a halt in week 12, 2020. In week 26, the breast program was resumed at 40% capacity, which increased to 60% in week 34. We examined the impact of the suspension and restart of the screening program on the incidence of screen-detected and non-screen-detected breast cancer. We selected women aged 50-74, diagnosed during weeks 2-35 of 2018 (n = 7250), 2019 (n = 7302), or 2020 (n = 5306), from the Netherlands Cancer Registry. Weeks 2-35 were divided in seven periods, based on events occurring at the start of the COVID-19 pandemic. Incidence of screen-detected and non-screen-detected tumors was calculated overall and by age group, cT-stage, and cTNM-stage for each period in 2020, and compared to the incidence in the same period of 2018/2019 (averaged). The incidence of screen-detected tumors decreased during weeks 12-13, reached almost zero during weeks 14-25, and increased during weeks 26-35. Incidence of non-screen-detected tumors decreased to a lesser extent during weeks 12-16. The decrease in incidence was seen in all age groups and mainly occurred for cTis, cT1 , DCIS, and stage I tumors. Due to the suspension of the breast cancer screening program, and the restart at reduced capacity, the incidence of screen-detected breast tumors decreased by 67% during weeks 9-35 2020, which equates to about 2000 potentially delayed breast cancer diagnoses. Up to August 2020 there was no indication of a shift towards higher stage breast cancers after restart of the screening., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objectives To investigate the impact of the population based breast screening programme on total uptake of mammography in the Netherlands. Setting The Netherlands; breast screening programme for women aged 50–69; 21 820 women who participated in the 1991–96 Health Interview Survey (HIS). Methods HIS data linked to data related to the start of the screening programme in different municipalities investigating mammography use, reasons for mammography, and further assessment procedures. Results Among women aged 50–69 the percentage who had recently undergone mammography (in the year of the HIS or two years before) increased from 20% in 1991 to 70% in 1996, which was entirely due to screening. The percentage of women in this age group who had had a recent clinical mammogram (outside the screening programme) varied between 8 and 12% and did not change significantly in municipalities without screening. There was no change in the uptake of mammography among women under 50 years of age. Among women over 70 there was only a small increase in this percentage from 6 to 13%, partially due to screening mammograms. In municipalities in which screening had started, precaution is mentioned as a reason for a recent clinical mammogram among women aged less than 70 more often than in municipalities without screening. Furthermore, mammography performed because of complaints is mentioned less in all age groups after the introduction of screening. After a clinical mammogram, further assessment procedures (cytology/needle biopsies 8%, biopsies 10%) were considered necessary about 10 times more often than after a screening mammogram. Conclusions Although the screening programme has almost no impact on the frequency of mammography in women who underwent a clinical mammogram, there has been a shift in reasons for these mammograms more towards reasons of prevention. Screening mammograms lead to a much smaller percentage of additional examinations than do clinical mammograms. [ABSTRACT FROM AUTHOR]

Objectives: Value of information (VOI) analysis can support health technology assessment decision making, but it is a long way from being standard use. The objective of this study was to understand barriers to the implementation of VOI analysis and propose actions to overcome these., Methods: We performed a process evaluation of VOI analysis use within decision making on tomosynthesis versus digital mammography for use in the Dutch breast cancer population screening. Based on steering committee meeting attendance and regular meetings with analysts, we developed a list of barriers to VOI use, which were analyzed using an established diffusion model. We proposed actions to address these barriers. Barriers and actions were discussed and validated in a workshop with stakeholders representing patients, clinicians, regulators, policy advisors, researchers, and the industry., Results: Consensus was reached on groups of barriers, which included characteristics of VOI analysis itself, stakeholder's attitudes, analysts' and policy makers' skills and knowledge, system readiness, and implementation in the organization. Observed barriers did not only pertain to VOI analysis itself but also to formulating the objective of the assessment, economic modeling, and broader aspects of uncertainty assessment. Actions to overcome these barriers related to organizational changes, knowledge transfer, cultural change, and tools., Conclusions: This in-depth analysis of barriers to implementation of VOI analysis and resulting actions and tools may be useful to health technology assessment organizations that wish to implement VOI analysis in technology assessment and research prioritization. Further research should focus on application and evaluation of the proposed actions in real-world assessment processes., (Copyright © 2021 ISPOR–The Professional Society for Health Economics and Outcomes Research. Published by Elsevier Inc. All rights reserved.)

One-size-fits-all breast cancer screening no longer reflects the current state of knowledge and technology. 8% of the participants in the Dutch Breastcancer Screening Program have extremely dense breasts, which is coupled to a strongly increased risk of breast cancer. In addition, for this group of approximately 80,000 women per year, mammography is only 60% sensitive. The DENSE trial showed that supplemental MRI after a negative mammogram reduced the number of interval cancers by more than 80%. The Dutch Health Council however subsequently recommended to consider contrast-enhanced mammography (CEM) as a screening tool. At the request of the Ministry of Health-Welfare and Sport, simultaneous research is being set up to study both CEM and the introduction of CEM and "accelerated" (abbreviated) MRI. This article explains the differences between the two techniques and discusses the role both could play in screening this large group of women when politicians give green light.

Background: To estimate the percentages of advanced-stage breast cancers (BCs) detected during the course of a steady-state screening programme when using different definitions of advanced BC., Methods: Data of women aged 49-74 years, diagnosed with BC in 2006-2015, were selected from the Netherlands Cancer Registry and linked to the screening registry. BCs were classified as screen-detected, interval or non-screened. Three definitions of advanced BC were used for comparison: TNM stage (III-IV), NM stage (N+ and/or M+) and T size (invasive tumour ≥15 mm). Analyses were performed assuming a 10% overdiagnosis rate. In sensitivity analyses, this assumption varied from 0 to 30%., Results: We included 46,734 screen-detected, 17,362 interval and 24,189 non-screened BCs. By TNM stage, 4.9% of screen-detected BCs were advanced, compared with 19.4% and 22.8% of interval and non-screened BCs, respectively (p < 0.001). Applying the other definitions led to higher percentages of advanced BC being detected. Depending on the definition interval, non-screened BCs had a 2-5-times risk of being advanced., Conclusion: Irrespective of the definition, screen-detected BCs were less frequently in the advanced stage. These findings provide evidence of a stage shift to early detection and support the potential of mammographic screening to reduce treatment-related burdens and the mortality associated with BC.

Background: In the Dutch breast cancer screening program, women recalled with a BI-RADS 0 score are referred for additional imaging, while those with BI-RADS 4/5 scores are also directed to an outpatient breast clinic. Approximately six out of ten women are recalled without being diagnosed with a malignancy. However, these recalls require additional imaging and doctor visits, which result in patient anxiety and increased health care costs. Conventional types of imaging used for additional imaging are full-field digital mammography and tomosynthesis. Contrast-enhanced spectral mammography has proved to have higher sensitivity and specificity than conventional imaging in women recalled from screening. Therefore, the aim is to study if CESM instead of conventional imaging is a more accurate, patient-friendly, and cost-effective strategy in the work-up of women recalled from breast cancer screening., Methods: This prospective, multicenter, randomized controlled trial will be conducted at four centers and will include 528 patients recalled for suspicious breast lesions from the Dutch breast cancer screening program. Participants are randomized in two groups: (1) standard care using conventional breast imaging techniques as initial imaging after recall versus (2) work-up primarily based on CESM. Written informed consent will be collected prior to study inclusion. The primary outcome is the diagnostic accuracy for detection of breast cancer. Secondary outcomes are numbers of additional diagnostic exams, days until final diagnosis, health care costs, and experienced patient anxiety., Discussion: Based on previously published retrospective studies, we expect to demonstrate in this prospective multicenter randomized controlled trial, that using CESM as a primary work-up tool in women recalled from breast cancer screening is a more accurate, cost-effective, and patient-friendly strategy., Trial Registration: Netherlands Trial Register, NL6413/NTR6589. Registered on 6 July, 2017.

High mammographic density is a well-known risk factor for breast cancer. This study aimed to search for a possible birth cohort effect on mammographic density, which might contribute to explain the increasing breast cancer incidence. We separately analyzed left and right breast density of Dutch women from a 13-year period (2003-2016) in the breast cancer screening programme. First, we analyzed age-specific changes in average percent dense volume (PDV) across birth cohorts. A linear regression analysis (PDV vs. year of birth) indicated a small but statistically significant increase in women of: 1) age 50 and born from 1952 to 1966 (left, slope = 0.04, p = 0.003; right, slope = 0.09, p < 0.0001); 2) age 55 and born from 1948 to 1961 (right, slope = 0.04, p = 0.01); and 3) age 70 and born from 1933 to 1946 (right, slope = 0.05, p = 0.002). A decrease of total breast volume seemed to explain the increase in PDV. Second, we compared proportion of women with dense breast in women born in 1946-1953 and 1959-1966, and observed a statistical significant increase of proportion of highly dense breast in later born women, in the 51 to 55 age-groups for the left breast (around a 20% increase in each age-group), and in the 50 to 56 age-groups for the right breast (increase ranging from 27% to 48%). The study indicated a slight increase in mammography density across birth cohorts, most pronounced for women in their early 50s, and more marked for the right than for the left breast., (© 2019 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)

Background: In the U.S., less educated women are substantially less likely to receive screening mammography. It is not clear whether this is due to differences in access to screening or in perceptions of breast cancer risks and the effectiveness of screening. We weigh the plausibility of these two explanations by examining how the dependence of mammography on education changes after conditioning on indicators of access and perceptions. We also compare estimates for the U.S. with those for the Netherlands where there is universal access to a publicly financed screening program. Method: Cross-sectional and cross-country comparable individual level data from the American Life Panel ( n = 646) and the Netherlands Longitudinal Internet Studies for the Social Sciences ( n = 1398) were used to estimate and explain education disparities in screening mammograms given to American and Dutch women aged 40+. The education gradient was estimated using logit models. Controls were sequentially added to detect whether disparities were explained by differences in access or perceptions of risks and effectiveness. Results: In the United States, high school graduates were 11.5 percentage points (95% CI: 1⁻22 percentage points) less likely than college graduates to receive a screening mammogram in the previous two years. This education gradient was largely explained by differences in income, insurance coverage and receipt of medical advice. It was not explained by educational differences in the perceived risk of breast cancer and the effectiveness of mammography. There were no education disparities in receipt of mammography among Dutch women within the 50⁻75 age range covered by the national screening program. Conclusion: In the absence of a universal screening program in the U.S., determinants of access-income, insurance coverage and receipt of medical advice-appear to drive the education disparities in screening mammography.

In this cross-sectional population-based study, we assessed the incidence of advanced breast cancer based on screening attendance. Women from the Netherlands Cancer Registry were included if aged ≥49 years and diagnosed with breast cancer between 2006 and 2011, and data were linked with the screening program. Cancers were defined as screen-related (diagnosed <24 months after screening) or nonscreened (all other breast cancers). Two cut-offs were used to define advanced breast cancer: TNM-stage (III-IV vs 0-I-II) and T-stage alone (≥15 mm vs <15 mm or DCIS). The incidence rates were adjusted for age and logistic regression was used to compare groups. Of the 72,612 included women diagnosed with breast cancer, 44,246 (61%) had screen-related breast cancer. By TNM stage, advanced cancer was almost three times as likely to be at an advanced TNM stage in the nonscreened group compared with the screen-related group (38 and 94 per 100,000, respectively; OR: 2.86, 95%CI: 2.72-3.00). By T-stage, the incidence of advanced cancer was higher overall, and in nonscreened women was significantly higher than in screened women (210 and 169 per 100,000; OR: 1.85, 95%CI: 1.78-1.93). Data on actual screening attendance showed that the incidence of advanced breast cancer was significantly higher in nonscreened women than in screened women, supporting the expectation that screening would cause a stage shift to early detection. Despite critical evaluations of breast cancer screening programs, our data show that breast cancer screening is a valuable tool that can reduce the disease burden in women., (© 2018 UICC.)

Objectives To investigate the risk of malignancy following stereotactic breast biopsy of calcifications classified as Breast Imaging Reporting and Data System (BI-RADS) 3, 4, and 5. Methods The study included women with pure calcifications (not associated with masses or architectural distortions) who underwent stereotactic breast biopsy at the Dutch Cancer Institute between January 2011 and October 2013. Suspicious calcifications (Breast Imaging Reporting and Data System 3, 4, or 5) detected on mammography were biopsied. All lesions were assessed by breast radiologists and classified according to the BI-RADS lexicon. Results Overall, 473 patients underwent 497 stereotactic breast biopsies. Sixty-six percent (326/497) of calcifications were classified B4, 30% (148/497) B3, and 4% (23/497) B5. Of the 226 (45%) malignant lesions, there were 182 pure ductal carcinoma in situ, 22 mixed ductal carcinoma in situ and invasive carcinomas (ductal or lobular), 21 pure invasive carcinomas, and one angiosarcoma. Malignancy was found in 32% (95% confidence interval [CI] 0.24 to 0.39) of B3, 49% (95% CI 0.43 to 0.54) of B4, and 83% (95% CI 0.61 to 0.95) of B5 calcifications. Conclusions Considering the high predictive value for malignancy in B3 calcifications, we propose that these lesions should be classified as suspicious (B4), especially in a screening setting.

The MISCAN-Fadia microsimulation model uses continuous tumor growth to simulate the natural history of breast cancer and has been used extensively to estimate the impact of screening and adjuvant treatment on breast cancer incidence and mortality trends. The model simulates individual life histories from birth to death, with and without breast cancer, in the presence and in the absence of screening and treatment. Life histories are simulated according to discrete events such as birth, tumor inception, the tumor's clinical diagnosis diameter in the absence of screening, and death from breast cancer or death from other causes. MISCAN-Fadia consists of 4 main components: demography, natural history of breast cancer, screening, and treatment. Screening impact on the natural history of breast cancer is assessed by simulating continuous tumor growth and the "fatal diameter" concept. This concept implies that tumors diagnosed at a size that is between the screen detection threshold and the fatal diameter are cured, while tumors diagnosed at a diameter larger than the fatal tumor diameter metastasize and lead to breast cancer death. MISCAN-Fadia has been extended by including a different natural history for molecular subtypes based on a tumor's estrogen receptor (ER) status and human epidermal growth factor receptor 2 (HER2) status. In addition, personalized screening strategies that target women based on their risk such as breast density have been incorporated into the model. This personalized approach to screening will continue to develop in light of potential polygenic risk stratification possibilities and new screening modalities.

Women with extremely dense breasts have an increased risk of breast cancer and lower mammographic tumor detectability. Nevertheless, in most countries, these women are currently screened with mammography only. Magnetic resonance (MR) imaging has the potential to improve breast cancer detection at an early stage because of its higher sensitivity. However, MR imaging is more expensive and is expected to be accompanied by an increase in the number of false-positive results and, possibly, an increase in overdiagnosis. To study the additional value of MR imaging, a randomized controlled trial (RCT) design is needed in which one group undergoes mammography and the other group undergoes mammography and MR imaging. With this design, it is possible to determine the proportion of interval cancers within each study arm. For this to be an effective screening strategy, the additional cancers detected at MR imaging screening must be accompanied by a subsequent reduction in interval cancers. The Dense Tissue and Early Breast Neoplasm Screening, or DENSE, trial is a multicenter RCT performed in the Dutch biennial population-based screening program (subject age range, 50-75 years). The study was approved by the Dutch Minister of Health, Welfare and Sport. In this study, mammographic density is measured by using a fully automated volumetric method. Participants with extremely dense breasts (American College of Radiology breast density category 4) and a negative result at mammography (Breast Imaging Recording and Data System category 1 or 2) are randomly assigned to undergo additional MR imaging (n = 7237) or to be treated according to current practice (n = 28 948). Participants provide written informed consent before the MR imaging examination, which consists of dynamic breast MR imaging with gadolinium-based contrast medium and is intended to be performed for three consecutive screening rounds. The primary outcome is the difference in the proportions of interval cancers between the study arms. Secondary outcomes are the number of MR imaging screening-detected cancers, proportions of false-positive results, diagnostic yield of MR imaging, tumor characteristics, quality of life, and cost effectiveness., (© RSNA, 2015)

Adjuvant systemic therapy has been shown to be effective in reducing breast cancer mortality. The additional effect of mammography screening remains uncertain, in particular for women aged 40-49 years. We therefore assessed the effects of screening starting between age 40 and 50, as compared to the effects of adjuvant systemic therapy. The use of adjuvant endocrine therapy, chemotherapy and the combination of endocrine- and chemotherapy, as well as the uptake of mammography screening in the Netherlands was modeled using micro-simulation. The effects of screening and treatment were modeled based on randomized controlled trials. The effects of adjuvant therapy, biennial screening between age 50 and 74 in the presence of adjuvant therapy, and extending the screening programme by starting at age 40 were assessed by comparing breast cancer mortality in women aged 0-100 years in scenarios with and without these interventions. In 2008, adjuvant treatment was estimated to have reduced the breast cancer mortality rate in the simulated population by 13.9%, compared to a situation without treatment. Biennial screening between age 50 and 74 further reduced the mortality rate by 15.7%. Extending screening to age 48 would lower the mortality rate by 1.0% compared to screening from age 50; 10 additional screening rounds between age 40 and 49 would reduce this rate by 5.1%. Adjuvant systemic therapy and screening reduced breast cancer mortality in similar amounts. Expanding the lower age limit of screening would further reduce breast cancer mortality., (© 2014 UICC.)

Annual MRI and mammography is recommended for BRCA1/2 mutation carriers to reduce breast cancer mortality. Less intensive screening is advised ≥60 years, although effectiveness is unknown. We identified BRCA1/2 mutation carriers without bilateral mastectomy before age 60 to determine for whom screening ≥60 is relevant, in the Rotterdam Family Cancer Clinic and HEBON: a nationwide prospective cohort study. Furthermore, we compared tumour stage at breast cancer diagnosis between different screening strategies in BRCA1/2 mutation carriers ≥60. Tumours >2 cm, positive lymph nodes, or distant metastases at detection were defined as "unfavourable." Of 548 BRCA1/2 mutation carriers ≥60 years in 2012, 395 (72%) did not have bilateral mastectomy before the age of 60. Of these 395, 224 (57%) had a history of breast or other invasive carcinoma. In 136 BRCA1/2 mutation carriers, we compared 148 breast cancers (including interval cancers) detected ≥60, of which 84 (57%) were first breast cancers. With biennial mammography 53% (30/57) of carcinomas were detected in unfavourable stage, compared to 21% (12/56) with annual mammography (adjusted odds ratio: 4·07, 95% confidence interval [1.79-9.28], p = 0.001). With biennial screening 40% of breast cancers were interval cancers, compared to 20% with annual screening (p = 0.016). Results remained significant for BRCA1 and BRCA2 mutation carriers, and first breast cancers separately. Over 70% of 60-year old BRCA1/2 mutation carriers remain at risk for breast cancer, of which half has prior cancers. When life expectancy is good, continuation of annual breast cancer screening of BRCA1/2 mutation carriers ≥60 is worthwhile., (© 2014 UICC.)

Background: To reduce mortality, women with a family history of breast cancer are often screened with mammography before age 50 years. Additional magnetic resonance imaging (MRI) improves sensitivity and is cost-effective for BRCA1/2 mutation carriers. However, for women with a family history without a proven mutation, cost-effectiveness is unclear., Methods: We evaluated data of the largest prospective MRI screening study (MRISC). Between 1999 and 2007, 1597 women (8370 woman-years at risk) aged 25 to 70 years with an estimated cumulative lifetime risk of 15% to 50% for breast cancer were screened with clinical breast examination every 6 months and with annual mammography and MRI. We calculated the cost per detected and treated breast cancer. After incorporating MRISC data into a microsimulation screening analysis model (MISCAN), different schemes were evaluated, and cost per life-year gained (LYG) was estimated in comparison with the Dutch nationwide breast cancer screening program (biennial mammography from age 50 to 75 years). All statistical tests were two-sided., Results: Forty-seven breast cancers (9 ductal carcinoma in situ) were detected. Screening with additional MRI costs $123 672 (€93 639) per detected breast cancer. In increasing age-cohorts, costs per detected and treated breast cancer decreased, but, unexpectedly, the percentage of MRI-only detected cancers increased. Screening under the MRISC-scheme from age 35 to 50 years was estimated to reduce breast cancer mortality by 25% at $134 932 (€102 164) per LYG (3.5% discounting) compared with 17% mortality reduction at $54 665 (€41 390) per LYG with mammography only., Conclusions: Screening with MRI may improve survival for women with familial risk for breast cancer but is expensive, especially in the youngest age categories.

Annually, in the Netherlands around 900,000 women between the ages of 50-75 years undergo mammography as part of a population screening into breast cancer. In this way more than 5000 cases of breast cancer are detected (0.6% of women screened); 70% of these malignancies are < stage II, which is prognostically favourable. Due to the early detection and treatment of breast cancer, the breast cancer death risk in those women who participate in the population screening is half that of women who choose not to be screened. The downside of the population screening is that participants are relatively often referred to a hospital for a diagnostic work-up (around 2%), and 70% of them are ultimately found not to have cancer. The positive predictive value of the population screening is 30%. Early discovery also leads to over-diagnosis in patients with breast cancer that without screening would never have manifested itself. Based on computer simulations it has been estimated that in the Netherlands over-diagnosis occurs in 9% of patients in whom breast cancer is detected during a population screening.

Although malpractice lawsuits are frequently related to a delayed breast cancer diagnosis in symptomatic patients, information on claims at European screening mammography programs is lacking. We determined the type and frequency of malpractice claims at a Dutch breast cancer screening region. We included all 85,274 women (351,009 screens) who underwent biennial screening mammography at a southern breast screening region in The Netherlands between 1997 and 2009. Two screening radiologists reviewed the screening mammograms of all screen detected cancers and interval cancers and determined whether the cancer had been missed at the previous screen or at the latest screen, respectively. We analyzed all correspondence between the screening organization, clinicians and screened women, and collected complaints and claims until September 2011. At review, 20.9% (308/1,475) of screen detected cancers and 24.3% (163/670) of interval cancers were considered to be missed at a previous screen. A total of 19 women (of which 2, 6 and 11 women had been screened between 1997 and 2001 (102,439 screens), 2001 and 2005 (114,740 screens) and 2005 and 2009 (133,830 screens), respectively) had contacted the screening organization for additional information about their screen detected cancer or interval cancer, but filed no claim. Three other women directly initiated an insurance claim for financial compensation of their interval cancer without previously having contacted the screening organization. We conclude that screening-related claims were rarely encountered, although many screen detected cancers and interval cancers had been missed at a previous screen. A small but increasing proportion of women sought additional information about their breast cancer from the screening organization., (Copyright © 2011 UICC.)

Background: Patients with a first episode of idiopathic venous thromboembolism (IVTE) have an estimated 10% incidence of cancer within 12 months after diagnosis. However, the utility of screening for cancer in this population is controversial., Methods: In this prospective concurrently controlled cohort study, limited and extensive cancer screening strategies were compared. All 630 patients underwent baseline screening consisting of history, physical examination, basic laboratory tests and chest X-ray. In the extensive screening group abdominal and chest CT scan and mammography were added. Outcomes were incidence and curability of cancer, and cancer-related and overall mortality., Results: In 12 of the 342 (3.5%) patients in the extensive screening group malignancy was diagnosed at baseline compared with 2.4% (seven of 288 patients) in the limited screening group. Extensive screening detected six additional cancers (2.0%; 95% CI, 0.74-4.3), of which three were potentially curable. During a median 2.5 years of follow-up, cancer was diagnosed in 3.7% and 5.0% in the extensive and limited screening groups, respectively. In the extensive screening group 26 patients (7.6%) died compared with 24 (8.3%) in the limited screening group; adjusted hazard ratio 1.22 (95% CI, 0.69-2.22). Of these deaths 17 (5.0%) in the extensive screening group and 8 (2.8%) in the limited screening group were cancer related; adjusted hazard ratio 1.79 (95% CI, 0.74-4.35)., Conclusions: The low yield of extensive screening and lack of survival benefit do not support routine screening for cancer with abdominal and chest CT scan and mammography in patients with a first episode of IVTE., (© 2010 International Society on Thrombosis and Haemostasis.)

Objective: We designed a case-referent study to investigate the effect of mammographic screening at the individual level, looking at the association of breast cancer death with screening history., Methods: The study population included all women aged 50-75 in the province of Limburg, the Netherlands who had been invited to the screening program from 1989 to 2006. From this population, 118 cases originated who died of breast cancer in 2004 or 2005. The screening history of these cases was collected and compared with a sample of the invited population. The breast cancer death rate in the screened relative to the unscreened women was estimated as the odds ratio (OR). This OR was adjusted for self-selection bias, the difference in baseline risk for breast cancer death between screened and unscreened women., Results: Analysis of the data showed a breast cancer mortality reduction of 70% in the screened versus the unscreened women (OR = 0.30, 95% CI 0.14-0.63). The magnitude of self-selection was estimated specifically for Limburg. After correction for self-selection bias, the effect of screening increased to 76% (OR = 0.24, 95% CI 0.10-0.58)., Conclusion: Screening resulted in a remarkable reduction in breast cancer mortality. Contrary to findings in other countries, adjustment for self-selection in Limburg had no influence on the impact of screening. Thanks to a well-organized centralized screening program, similar results are expected in other regions of the Netherlands.

Purpose: To determine the contribution of surveillance mammography to the early detection of metachronous contralateral breast cancer (MCBC) and to assess its impact on the survival of breast cancer patients with relation to compliance., Method: Breast cancer patients (5589) were identified using files from the regional cancer registry of the Comprehensive Cancer Centre North Netherlands (CCCN Groningen, The Netherlands). The programme sensitivity and the impact on prognosis of follow-up mammography with relation to compliance were evaluated in 114 patients who developed MCBC during hospital follow-up., Results: The cumulative MCBC incidence rate at year 10 was 3.4% (95% CI: 2.8-4.0%). The programme sensitivity of surveillance mammography was 59.6% (95% CI: 50.6-68.7). In patients who complied with annual mammography, sensitivity was increased to 70.8% (95% CI: 61.7-80.0). Patients with MCBCs detected by routine mammography have better survival rates than patients with MCBCs detected by other means (HR: 3.18; 95% CI: 1.59-6.34). Though there was a trend towards improved survival in patients being compliant with regular clinical follow-up (HR: 1.69; 95% CI: 0.72-3.96), this was not the case for patients being compliant with annual mammography (HR:1.02; 95% CI:0.50-2.09)., Conclusion: Mammography is a valuable tool for the early detection of MCBC during hospital follow-up of breast cancer patients and is probably beneficial to survival. The utilisation of follow-up surveillance in breast cancer patients and its potential impact on survival deserve further investigation.

Breast cancer is the most prevalent malignancy among Dutch women; life prevalence is about 10%. A tumour in the breast of a woman of 35 years or older is always an indication for mammography, while a woman younger than 35 should have an ultrasound investigation. This is also the case if the woman can feel the tumour but the doctor is unable to. In breast pain without palpable abnormalities at physical examination, the risk of breast cancer is a lot lower and diagnostics may not need to be instigated immediately. However, persistent localized pain is an indication for breast imaging. Women with at least a doubled risk of getting breast cancer due to the occurrence of breast cancer in their relatives are recommended to undergo mammography every year from the ages of 40-49 years supplementary to the national screening programme. The Dutch national screening programme invites women aged between 50 and 75 to undergo mammography every two years. Follow-up of women of 60 years and older treated by lumpectomy 5 years or more previously, can be done by the general practitioner.

Background: In 2003, for the first time, US breast cancer incidence rates have fallen. Experts argue whether this is due to the reduced uptake of screening mammography or to lower use of Hormone Replacement Therapy (HRT). This study aims to disentangle the respective impact of screening and HRT on age-incidence rates and histology of breast cancer, by comparing two populations with comparably high levels of screening mammography, but with different prevalence of HRT., Methods: We included all invasive breast cancers recorded at the Geneva cancer registry (n = 4,909) and the Netherlands Cancer Registry (n = 152,428) between 1989-2003. We compared age-specific incidence rates and trends in histological subtyping between the two populations., Results: Between 1989-1991, incidence rates increased with age in both populations. In 2001-2003, women aged 60-64 years showed highest incidence rates in Geneva, while in the Netherlands incidence rates continued to increase with age. The annual increase in ductal cancer incidence was similar in the Netherlands (2.3%) and Geneva (2.5%), but the annual increase in lobular cancer was sharper in Geneva (10%) than in the Netherlands (5%)., Conclusion: The sharp differences in age distribution and histological subtyping of breast cancer between two European populations are not attributable to screening, since both populations have a high uptake of mammography screening. Since the prevalence of HRT use is very high in Geneva and rather low in the Netherlands, HRT may explain these discrepancies. However, other etiological factors and differences in histological assessment may also have played a role.

Purpose: In a prospective, multi-institutional follow-up study we describe the trends in the preoperative pathologic confirmation of breast cancer of women who underwent breast cancer screening between 1995 and 2005., Methods: We included all women aged 50-75 years who underwent biennial screening mammography in the southern breast cancer screening region of the Netherlands between February 13, 1995 and December 22, 2004. Clinical data, breast imaging reports, biopsy results and breast surgery reports were collected of all women with a positive screening result. Follow-up lasted through the next biennial screening examination and was approximately two years for all referred women., Results: Of 258,900 mammographic screening examinations, 3,064 (1.2%) were positive screens. The majority of women (92%) were analyzed in four regional hospitals and workup yielded breast cancer in 1,332 women. From 1995 to 2005, the percentage of breast cancer cases that underwent percutaneous biopsy prior to surgery, increased from 42.4 to 100%. The proportion of cancers with a preoperative diagnosis of malignancy by percutaneous biopsy, increased from 27.1% in 1995 to 92.7% in 2004. Preoperative breast cancer confirmation by fine needle aspiration cytology (FNAC) gradually decreased from 91.3% to 14.5%, whereas preoperative confirmation by ultrasound guided core biopsy (USCB) or stereotactic core needle biopsy (SCNB) increased from 8.7% to 69.1% and from 0 to 17.4% respectively., Conclusions: A preoperative diagnosis of breast cancer is currently obtained in more than 90% of breast cancer patients. The increase in preoperative breast cancer diagnosis through 1995-2004 is correlated with the introduction of SNCB and increased use of USCB at the expense of FNAC.

Background: Studies have shown that having mammography technologists review screening mammograms in addition to radiologist review may increase the number of breast cancers that are detected at screening mammography. We prospectively examined the effects on screening performance of adding independent double reading of screening mammograms by technologists to standard double reading by radiologists., Methods: Twenty-one screening mammography technologists and eight certified screening radiologists participated in this study. From January 1, 2003, to January 1, 2005, all 61,251 screening mammograms obtained at two mammography screening units in The Netherlands were independently read (although the second reader was not blinded to the first reader's interpretation) by two technologists and, in turn, by two radiologists. Radiologists were blinded to the referral opinion of the technologists. During a 2-year follow-up period, we collected clinical data, breast imaging reports, biopsy results, and breast surgery reports of all women with a positive screening result (i.e., those that required additional imaging) from any reader. The distributions of categorical variables between subgroups were compared using chi-square or Fisher's exact tests. Differences in referral and detection by radiologists and technologists were assessed using McNemar's test. All statistical tests were two-sided., Results: The radiologists referred 905 women (referral rate = 1.48%, 95% confidence interval [CI] = 1.38% to 1.57%), of whom 323 had breast cancer, corresponding to a positive predictive value of referral (PPV) of 35.7% (95% CI = 32.6% to 38.8%). Review of 446 additional technologist-positive readings led to another 80 referrals, resulting in the detection of 22 additional cancers. These extra referrals increased the initial referral rate from 1.48% to 1.61% (difference = 0.13%; 95% CI = 0.10% to 0.16%) and the cancer detection rate (CDR) from 5.27 to 5.63 cancers per 1000 women screened (difference = 0.36 cancers per 1000 women screened; 95% CI = 0.24 to 0.55). With technologist double reading only, 829 women would have been referred (referral rate = 1.35%, 95% CI = 1.26% to 1.45%); among these women, 286 cancers were diagnosed (PPV = 34.5%, 95% CI = 31.3% to 37.7%; CDR = 4.67 cancers per 1000 women screened, 95% CI = 4.13 to 5.21). Referral of all 1351 radiologist- and/or technologist-positive readings would have led to 362 cancers found at screening. The cancer detection rate for radiologist double reading would have increased from 5.27 to 5.91 cancers per 1000 women screened (relative increase = 12.1%, 95% CI = 8.8% to 16.5%; difference = 0.64 cancers per 1000 women screened, 95% CI = 0.47 to 0.87)., Conclusion: A referral strategy that includes all technologist-positive readings, which would have increased the cancer detection rate while maintaining a low referral rate, should be considered.

Background: After curative treatment for breast cancer women frequently attend scheduled follow-up examinations. Usually the follow-up is most frequent in the first 2-3 years (2-4 times a year); thereafter the frequency is reduced to once a year in most countries. Its main aim is to detect local disease recurrence, or a second primary breast cancer, but also to provide information and psychosocial support. However, the cost-effectiveness of these frequent visits is under much debate, leading to a search for less intensive and more cost-effective follow-up strategies. In this paper the design of the MaCare trial is described. This trial compares the cost-effectiveness of four follow-up strategies for curatively treated breast cancer patients. We investigate the costs and effects of nurse-led telephone follow-up and a short educational group programme., Methods/design: The MaCare trial is a multi centre randomised clinical trial in which 320 breast cancer patients are randomised into four follow-up strategies, focussed on the first 18 months after treatment: 1) standard follow-up; 2) nurse-led telephone follow-up; 3) arm 1 with the educational group programme; 4) arm 2 with the educational group programme. Data is collected at baseline and 3, 6, 12 and 18 months after treatment. The primary endpoint of the trial is cancer-specific quality of life as measured by the global health/QoL scale of the EORTC QLQ-C30. Secondary outcomes are perceived feelings of control, anxiety, patients' satisfaction with follow-up and costs. A cost-effectiveness analysis will be performed from a societal perspective., Discussion: Reduced follow-up strategies for breast cancer have not yet been widely applied in clinical practice. Improvement of psychosocial support and information to patients could lead to a better acceptance of reduced follow-up. The MaCare trial combines a reduced follow-up strategy with additional psychosocial support. Less frequent follow-up can reduce the burden on medical specialists and costs. The educational group programme can improve QoL of patients, but also less frequent follow-up can improve QoL by reducing the anxiety experienced for each follow-up visit. Results of the trial will provide knowledge on both costs and psychosocial aspects regarding follow-up and are expected in 2009.

The nationwide breast cancer screening programme using mammography has been in full operation in The Netherlands since 1997. There is concern that the mean glandular doses due to mammography might be differing between different regions of the country due to differences in glandularity and compressed breast thickness. To investigate regional differences, glandularity, compressed breast thickness and mean glandular dose were determined for individual breasts during screening at mammography units at four locations in The Netherlands. Differences in glandularity were observed, which could be related qualitatively to differences in age of the participants at the different locations. Mean glandular dose depends on compressed breast thickness, glandularity and technical conditions of screening. The lowest average value of the mean glandular dose was found for the unit in Amsterdam. This is most likely due to the use of the Mo/Rh anode/filter combination at this unit, in addition to the Mo/Mo combination. At the other three units, almost exclusively the Mo/Mo anode/filter combination was used. Differences in mean glandular dose averaged per unit could be related mainly to differences in tube-current exposure-time product values. Consequently, it is concluded that differences in mean glandular dose at different units are marginal.