The importance of early detection of calcifications associated with breast cancer in screening.

PURPOSE: The aim of this study was to assess how often women with undetected calcifications in prior screening mammograms are subsequently diagnosed with invasive cancer. METHODS: From a screening cohort of 63,895 women, exams were collected from 59,690 women without any abnormalities, 744 women with a screen-detected cancer and a prior negative exam, 781 women with a false positive exam based on calcifications, and 413 women with an interval cancer. A radiologist identified cancer-related calcifications, selected by a computer-aided detection system, on mammograms taken prior to screen-detected or interval cancer diagnoses. Using this ground truth and the pathology reports, the sensitivity for calcification detection and the proportion of lesions with visible calcifications that developed into invasive cancer were determined. RESULTS: The screening sensitivity for calcifications was 45.5%, at a specificity of 99.5%. A total of 68.4% (n = 177) of cancer-related calcifications that could have been detected earlier were associated with invasive cancer when diagnosed. CONCLUSIONS: Screening sensitivity for detection of malignant calcifications is low. Improving the detection of these early signs of cancer is important, because the majority of lesions with detectable calcifications that are not recalled immediately but detected as interval cancer or in the next screening round are invasive at the time of diagnosis.

The impact of mammography screening programmes on incidence of advanced breast cancer in Europe: a literature review.

BACKGROUND: Observational studies have reported conflicting results on the impact of mammography service screening programmes on the advanced breast cancer rate (ABCR), a correlation that was firmly established in randomized controlled trials. We reviewed and summarized studies of the effect of service screening programmes in the European Union on ABCR and discussed their limitations. METHODS: The PubMed database was searched for English language studies published between 01-01-2000 and 01-06-2018. After inspection of titles and abstracts, 220 of the 8644 potentially eligible papers were considered relevant. Their abstracts were reviewed by groups of two authors using predefined criteria. Fifty studies were selected for full paper review, and 22 of these were eligible. A theoretical framework for their review was developed. Review was performed using a ten-point checklist of the methodological caveats in the analysis of studies of ABCR and a standardised assessment form designed to extract quantitative and qualitative information. RESULTS: Most of the evaluable studies support a reduction in ABCR following the introduction of screening. However, all studies were challenged by issues of design and analysis which could at least potentially cause bias, and showed considerable variation in the estimated effect. Problems were observed in duration of follow-up time, availability of reliable reference ABCR, definition of advanced stage, temporal variation in the proportion of unknown-stage cancers, and statistical approach. CONCLUSIONS: We conclude that much of the current controversy on the impact of service screening programmes on ABCR is due to observational data that were gathered and/or analysed with methodological approaches which could not capture stage effects in full. Future research on this important early indicator of screening effectiveness should focus on establishing consensus in the correct methodology.

The distribution of ductal carcinoma in situ (DCIS) grade in 4232 women and its impact on overdiagnosis in breast cancer screening.

BACKGROUND: The incidence of ductal carcinoma in situ (DCIS) has rapidly increased over time. The malignant potential of DCIS is dependent on its differentiation grade. METHODS: Our aim is to determine the distribution of different grades of DCIS among women screened in the mass screening programme, and women not screened in the mass screening programme, and to estimate the amount of overdiagnosis by grade of DCIS. We retrospectively included a population-based sample of 4232 women with a diagnosis of DCIS in the years 2007-2009 from the Nationwide network and registry of histopathology and cytopathology in the Netherlands. Excluded were women with concurrent invasive breast cancer, lobular carcinoma in situ and no DCIS, women recently treated for invasive breast cancer, no grade mentioned in the record, inconclusive record on invasion, and prevalent DCIS. The screening status was obtained via the screening organisations. The distribution of grades was incorporated in the well-established and validated microsimulation model MISCAN. RESULTS: Overall, 17.7 % of DCIS were low grade, 31.4 % intermediate grade, and 50.9 % high grade. This distribution did not differ by screening status, but did vary by age. Older women were more likely to have low-grade DCIS than younger women. Overdiagnosis as a proportion of all cancers in women of the screening age was 61 % for low-grade, 57 % for intermediate-grade, 45 % for high-grade DCIS. For women age 50-60 years with a high-grade DCIS this overdiagnosis rate was 21-29 %, compared to 50-66 % in women age 60-75 years with high-grade DCIS. CONCLUSIONS: Amongst the rapidly increasing numbers of DCIS diagnosed each year is a significant number of overdiagnosed cases. Tailoring treatment to the probability of progression is the next step to preventing overtreatment. The basis of this tailoring could be DCIS grade and age.

Overdiagnosis by mammographic screening for breast cancer studied in birth cohorts in The Netherlands.

A drawback of early detection of breast cancer through mammographic screening is the diagnosis of breast cancers that would never have become clinically detected. This phenomenon, called overdiagnosis, is ideally quantified from the breast cancer incidence of screened and unscreened cohorts of women with follow-up until death. Such cohorts do not exist, requiring other methods to estimate overdiagnosis. We are the first to quantify overdiagnosis from invasive breast cancer and ductal carcinoma in situ (DCIS) in birth cohorts using an age-period-cohort -model (APC-model) including variables for the initial and subsequent screening rounds and a 5-year period after leaving screening. Data on the female population and breast cancer incidence were obtained from Statistics Netherlands, "Stichting Medische registratie" and the Dutch Cancer Registry for women aged 0-99 years. Data on screening participation was obtained from the five regional screening organizations. Overdiagnosis was calculated from the excess breast cancer incidence in the screened group divided by the breast cancer incidence in presence of screening for women aged 20-99 years (population perspective) and for women in the screened-age range (individual perspective). Overdiagnosis of invasive breast cancer was 11% from the population perspective and 17% from the invited women perspective in birth cohorts screened from age 49 to 74. For invasive breast cancer and DCIS together, overdiagnosis was 14% from population perspective and 22% from invited women perspective. A major strength of an APC-model including the different phases of screening is that it allows to estimate overdiagnosis in birth cohorts, thereby preventing overestimation.

Experiences with a self-test for Dutch breast screening radiologists: lessons learnt.

PURPOSE: To evaluate a self-test for Dutch breast screening radiologists introduced as part of the national quality assurance programme. METHODS AND MATERIALS: A total of 144 radiologists were invited to complete a test-set of 60 screening mammograms (20 malignancies). Participants assigned findings such as location, lesion type and BI-RADS. We determined areas under the receiver operating characteristics (ROC) curves (AUC), case and lesion sensitivity and specificity, agreement (kappa) and correlation between reader characteristics and case sensitivity (Spearman correlation coefficients). RESULTS: A total of 110 radiologists completed the test (76%). Participants read a median number of 10,000 screening mammograms/year. Median AUC value was 0.93, case and lesion sensitivity was 91% and case specificity 94%. We found substantial agreement for recall (κ = 0.77) and laterality (κ = 0.80), moderate agreement for lesion type (κ = 0.57) and BI-RADS (κ = 0.45) and no correlation between case sensitivity and reader characteristics. CONCLUSION: Areas under the ROC curve, case sensitivity and lesion sensitivity were satisfactory and recall agreement was substantial. However, agreement in lesion type and BI-RADS could be improved; further education might be aimed at reducing interobserver variation in interpretation and description of abnormalities. We offered individual feedback on interpretive performance and overall feedback at group level. Future research will determine whether performance has improved. KEY POINTS: • We introduced and evaluated a self-test for Dutch breast screening radiologists. • ROC curves, case and lesion sensitivity and recall agreement were all satisfactory. • Agreement in BI-RADS interpretation and description of abnormalities could be improved. • These are areas that should be targeted with further education and training. • We offered individual feedback on interpretative performance and overall group feedback.

Variations in screening outcome among pairs of screening radiologists at non-blinded double reading of screening mammograms: a population-based study.

OBJECTIVES: Substantial inter-observer variability in screening mammography interpretation has been reported at single reading. However, screening results of pairs of screening radiologists have not yet been published. We determined variations in screening performances among pairs of screening radiologists at non-blinded double reading. METHODS: We included pairs of screening radiologists with at least 7,500 screening examinations per pair, obtained between 1997 and 2011. During 2-year follow-up, breast imaging reports, surgical reports and pathology results were collected of all referred women and interval cancers. Referral rate, cancer detection rate, positive predictive value and sensitivity were calculated for each pair. RESULTS: A total of 310,906 screening mammograms, read by 26 pairs of screening radiologists, were included for analysis. The referral rate ranged from 1.0 % (95 % CI 0.8 %-1.2 %) to 1.5 % (95 % CI 1.3 %-1.8 %), the cancer detection rate from 4.0 (95 % CI 2.8-5.2) to 6.3 (95 % CI 4.5-8.0) per 1,000 screens. The programme sensitivity and positive predictive value of referral ranged from 55.1 % (95 % CI 45.1 %-65.1 %) to 81.5 % (95 % CI 73.4 %-89.6 %) and from 28.7 % (95 % CI 20.8 %-36.6 %) to 49.5 % (95 % CI 39.7 %-59.3 %), respectively. CONCLUSION: We found significant variations in screening outcomes among pairs of screening radiologists at non-blinded double reading. This stresses the importance of monitoring screening results on a local scale. KEY POINTS: • Substantial inter-observer variability in screening mammography interpretation is known at single reading • Population-based study showed significant variations in outcomes among pairs of screening radiologists • Local monitoring and regular feedback are important to optimise screening outcome.

Immediate and delayed effects of mammographic screening on breast cancer mortality and incidence in birth cohorts.

BACKGROUND: Trend studies investigating the impact of mammographic screening usually display age-specific mortality and incidence rates over time, resulting in an underestimate of the benefit of screening, that is, mortality reduction, and an overestimate of its major harmful effect, that is, overdiagnosis. This study proposes a more appropriate way of analysing trends. METHODS: Breast cancer mortality (1950-2009) and incidence data (1975-2009) were obtained from Statistics Netherlands, 'Stg. Medische registratie' and the National Cancer Registry in the Netherlands for women aged 25-85 years. Data were visualised in age-birth cohort and age-period figures. RESULTS: Birth cohorts invited to participate in the mammographic screening programme showed a deflection in the breast cancer mortality rates within the first 5 years after invitation. Thereafter, the mortality rate increased, although less rapidly than in uninvited birth cohorts. Furthermore, invited birth cohorts showed a sharp increase in invasive breast cancer incidence rate during the first 5 years of invitation, followed by a moderate increase during the following screening years and a decline after passing the upper age limit. CONCLUSION: When applying a trend study to estimate the impact of mammographic screening, we recommend using a birth cohort approach.

Likelihood of early detection of breast cancer in relation to false-positive risk in life-time mammographic screening: population-based cohort study.

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.

Breast cancer risk prediction model: a nomogram based on common mammographic screening findings.

OBJECTIVES: To develop a prediction model for breast cancer based on common mammographic findings on screening mammograms aiming to reduce reader variability in assigning BI-RADS. METHODS: We retrospectively reviewed 352 positive screening mammograms of women participating in the Dutch screening programme (Nijmegen region, 2006-2008). The following mammographic findings were assessed by consensus reading of three expert radiologists: masses and mass density, calcifications, architectural distortion, focal asymmetry and mammographic density, and BI-RADS. Data on age, diagnostic workup and final diagnosis were collected from patient records. Multivariate logistic regression analyses were used to build a breast cancer prediction model, presented as a nomogram. RESULTS: Breast cancer was diagnosed in 108 cases (31 %). The highest positive predictive value (PPV) was found for spiculated masses (96 %) and the lowest for well-defined masses (10 %). Characteristics included in the nomogram are age, mass, calcifications, architectural distortion and focal asymmetry. CONCLUSION: With our nomogram we developed a tool assisting screening radiologists in determining the chance of malignancy based on mammographic findings. We propose cutoff values for assigning BI-RADS in the Dutch programme based on our nomogram, which will need to be validated in future research. These values can easily be adapted for use in other screening programmes. KEY POINTS: • There is substantial reader variability in assigning BI-RADS in mammographic screening. • There are no strict guidelines linking mammographic findings to BI-RADS categories. • We developed a model (nomogram) predicting the presence of breast cancer. • Our nomogram is based on common findings on positive screening mammograms. • The nomogram aims to assist screening radiologists in assigning BI-RADS categories.

The Breast Imaging Reporting and Data System (BI-RADS) in the Dutch breast cancer screening programme: its role as an assessment and stratification tool.

OBJECTIVES: To assess the suitability of the Breast Imaging Reporting and Data System (BI-RADS) as a quality assessment tool in the Dutch breast cancer screening programme. METHODS: The data of 93,793 screened women in the Amsterdam screening region (November 2005-July 2006) were reviewed. BI-RADS categories, work-up, age, final diagnosis and final TNM classification were available from the screening registry. Interval cancers were obtained through linkage with the cancer registry. BI-RADS was introduced as a pilot in the Amsterdam region before the nationwide introduction of digital mammography (2009-2010). RESULTS: A total of 1,559 women were referred to hospital (referral rate 1.7 %). Breast cancer was diagnosed in 485 women (detection rate 0.52 %); 253 interval cancers were reported, yielding a programme sensitivity of 66 % and specificity of 99 %. BI-RADS 0 had a lower positive predictive value (PPV, 14.1 %) than BI-RADS 4 (39.1 %) and BI-RADS 5 (92.9 %; P < 0.0001). The number of invasive procedures and tumour size also differed significantly between BI-RADS categories (P < 0.0001). CONCLUSION: The significant differences in PPV, invasive procedures and tumour size match with stratification into BI-RADS categories. It revealed inter-observer variability between screening radiologists and can thus be used as a quality assessment tool in screening and as a stratification tool in diagnostic work-up. KEY POINTS: • The BI-RADS atlas is widely used in breast cancer screening programmes. • There were significant differences in results amongst different BI-RADS categories. • Those differences represented the radiologists' degree of suspicion for malignancy, thus enabling stratification of referrals. • BI-RADS can be used as a quality assessment tool in screening. • Training should create more uniformity in applying the BI-RADS lexicon.

Increasingly strong reduction in breast cancer mortality due to screening.

BACKGROUND: Favourable outcomes of breast cancer screening trials in the 1970s and 1980s resulted in the launch of population-based service screening programmes in many Western countries. We investigated whether improvements in mammography and treatment modalities have had an influence on the effectiveness of breast cancer screening from 1975 to 2008. METHODS: In Nijmegen, the Netherlands, 55,529 women received an invitation for screening between 1975 and 2008. We designed a case-referent study to evaluate the impact of mammographic screening on breast cancer mortality over time from 1975 to 2008. A total number of 282 breast cancer deaths were identified, and 1410 referents aged 50-69 were sampled from the population invited for screening. We estimated the effectiveness by calculating the odds ratio (OR) indicating the breast cancer death rate for screened vs unscreened women. RESULTS: The breast cancer death rate in the screened group over the complete period was 35% lower than in the unscreened group (OR=0.65; 95% CI=0.49-0.87). Analysis by calendar year showed an increasing effectiveness from a 28% reduction in breast cancer mortality in the period 1975-1991 (OR=0.72; 95% CI=0.47-1.09) to 65% in the period 1992-2008 (OR=0.35; 95% CI=0.19-0.64). CONCLUSION: Our results show an increasingly strong reduction in breast cancer mortality over time because of mammographic screening.

Breast cancer screening case-control study design: impact on breast cancer mortality.

BACKGROUND: Recent case-control studies on the effectiveness of population-based breast cancer screening show differences in the magnitude of breast cancer mortality reduction. We investigated the role played by aspects of the case-control study design on these differences, e.g. the definition of cases and exposure to screening. MATERIAL AND METHODS: We investigated six case-control studies conducted in East Anglia (UK), Wales, Iceland, central and northern Italy, South Australia and The Netherlands. RESULTS: The breast cancer mortality reduction in the different case-control studies ranged from 38% to 70% in the screened versus the nonscreened women. We identified differences in design, e.g. the inclusion or exclusion of the first years of screening, and the correction factor for self-selection bias. CONCLUSIONS: Overall, the design of the case-control studies was similar. The differences in the magnitude of breast cancer mortality reductions are therefore unlikely to be caused by variations in the design of the case-control studies. These differences must be due to other factors, like the organisation of the service screening programme and the attendance rate. The reduction in breast cancer mortality estimated in these case-control studies indicates that the impact of current mammographic screening is at least consistent with the effect reported by the former randomised screening trials.

Trends in delayed breast cancer diagnosis after recall at screening mammography.

OBJECTIVES: To determine the extent and characteristics of delay in breast cancer diagnosis in women recalled at screening mammography. METHODS: We included a consecutive series of 817,656 screens of women who received biennial screening mammography in a Dutch breast cancer screening region between 1997 and 2016. During at least 3.5 years follow-up, radiological reports and biopsy reports were collected of all recalled women. The inclusion period was divided into four cohorts of four years each. We determined the number of screen-detected cancers and their characteristics, and assessed the proportion of recalled women who experienced a diagnostic delay of at least 4 months in breast cancer confirmation. RESULTS: The proportion of recalled women who experienced diagnostic delay decreased from 7.5 % in 1997-2001 (47/623) to 3.0 % in 2012-2016 (67/2223, P < 0.001). The proportion of women with a delay of at least two years increased from 27.7 % (13/47) in 1997-2001 to 75.7 % (53/70) in 2012-2016 (P < 0.001). Cancers with a diagnostic delay > 2 years were more frequently invasive (P = 0.009) than cancers with a diagnostic delay of 4-24 months. The most frequent cause of diagnostic delays was incorrect radiological classifications by clinical radiologists (55.2 % overall) after recall. CONCLUSIONS: The proportion of recalled women with a delayed breast cancer diagnosis has more than halved during two decades of screening mammography. Delays in breast cancer diagnosis are characterized by longer delay intervals, although the proportion of these delays among all screen-detected cancers has not increased. Preventing longer delays in breast cancer confirmation may help improve breast cancer survival.

Towards evidence-based follow-up intervals for breast cancer survivors: Estimates of the preclinical detectable phase of contralateral second breast cancer.

PURPOSE: Follow-up schemes in breast cancer survivors are predominantly consensus-based. To determine evidence-based follow-up intervals, estimates of sensitivity of the screening test(s) and duration of the preclinical detectable phase (PCDP) are key. We estimated the sensitivity and the duration of the PCDP of clinical breast examination (CBE) and mammography for the detection of contralateral second breast cancers (CBC) in breast cancer survivors. METHODS: Women with a CBC (N = 589) diagnosed in Florence between 1980 and 2005 were included. Test sensitivity and the duration of PCDP were estimated using a simple exponential model of PCDP duration. Analyses were stratified by follow-up period (0-5 vs. >5 years after primary diagnosis) and age at CBC diagnosis (<50 vs. ≥50 years). RESULTS: For CBE, test sensitivity was 55% and the duration of the PCDP 16 months. Mammography sensitivity was 91% and duration of the PCDP 35 months. Stratified analyses showed a higher test sensitivity for CBE for women aged <50 (70% vs. 51%). No difference in the duration of PCDP of CBE was found. For mammography, test sensitivity and the duration of the PCDP were higher for women with longer follow-up and in older women. CONCLUSIONS: Poor test sensitivity for CBE with a shorter duration of the PCDP compared with mammography were observed. Mammography had high test sensitivity and the potential to detect CBCs early. The estimated duration of the PCDP (35 months) was considerably longer than the recommended follow-up interval (12 months). Future studies are needed to determine whether a longer follow-up interval is appropriate.

Can a channelized Hotelling observer assess image quality in acquired mammographic images of an anthropomorphic breast phantom including image processing?

PURPOSE: To study the feasibility of a channelized Hotelling observer (CHO) to predict human observer performance in detecting calcification-like signals in mammography images of an anthropomorphic breast phantom, as part of a quality control (QC) framework. METHODS: A prototype anthropomorphic breast phantom with inserted gold disks of 0.25 mm diameter was imaged with two different digital mammography x-ray systems at four different dose levels. Regions of interest (ROIs) were extracted from the acquired processed and unprocessed images, signal-present and signal-absent. The ROIs were evaluated by a CHO using four different formulations of the difference of Gaussian (DoG) channel sets. Three human observers scored the ROIs in a two-alternative forced-choice experiment. We compared the human and the CHO performance on the simple task to detect calcification-like disks in ROIs with and without postprocessing. The proportion of correct responses of the human reader (PCH ) and the CHO (PCCHO ) was calculated and the correlation between the two was analyzed using a mixed-effect regression model. To address the signal location uncertainty, the impact of shifting the DoG channel sets in all directions up to two pixels was evaluated. Correlation results including the goodness of fit (r2 ) of PCH and PCCHO for all different parameters were evaluated. RESULTS: Subanalysis by system yielded strong correlations between PCH and PCCHO , with r2 between PCH and PCCHO was found to be between 0.926 and 0.958 for the unshifted and between 0.759 and 0.938 for the shifted channel sets, respectively. However, the linear fit suggested a slight system dependence. PCCHO with shifted channel sets increased CHO performance but the correlation with humans was decreased. These correlations were not considerably affected by of the DoG channel set used. CONCLUSIONS: There is potential for the CHO to be used in QC for the evaluation of detectability of calcification-like signals. The CHO can predict the PC of humans in images of calcification-like signals of two different systems. However, a global model to be used for all systems requires further investigation.

Large increase in a Dutch woman's lifetime risk of developing breast cancer.

A large increase in the incidence of breast cancer has been observed in many countries over the last two decades. On the other hand, however, breast cancer mortality has decreased. The prominent burden of breast cancer in the female population induces a lot of discussion about incidence and mortality rates, whereas lifetime risks are less mentioned. This study provides information on the changes in risks for Dutch women with regards to being diagnosed with breast cancer (both invasive and in situ) or dying from this disease during the screening era. We used the life table method to calculate lifetime risks for the period 1989-2003. The lifetime risk for developing breast cancer increased from 1 in 10 in 1989 to 1 in 7 in 2003; the risk of dying from breast cancer decreased respectively from 1 in 22 to 1 in 26. The increasing incidence is alarming but has to be seen in perspective; the decreasing mortality is promising and shows that, at most, one third of the breast cancer cases are fatal.

Can the channelized Hotelling observer including aspects of the human visual system predict human observer performance in mammography?

PURPOSE: In mammography, images are processed prior to display. Model observers (MO) are candidates to objectively evaluate processed images if they can predict human observer performance for detail detection. The aim of this study was to investigate if the channelized Hotelling observer (CHO) can be configured to predict human observer performance in mammography like images. METHODS: The performance correlation between human observers and CHO has been evaluated using different channel-sets and by including aspects of the human visual system (HVS). The correlation was investigated for the detection of disk-shaped details in simulated white noise (WN) and clustered lumpy backgrounds (CLB) images, representing respectively quantum noise limited and mammography like images. The images were scored by the MO and five human observers in 2-alternative forced choice experiments. RESULTS: For WN images the most useful formulation of the CHO to predict human observer performance was obtained using three difference of Gaussian channels without adding HVS aspects (RLR2=0.62). For CLB images the most useful formulation was the partial least square channel-set without adding HVS aspects (RLR2=0.71). The correlation was affected by detail size and background. CONCLUSIONS: This study has shown that the CHO can predict human observer performance. Due to object size and background dependency it is important that the range of object sizes and allowed variability in background are specified and validated carefully before the CHO can be implemented for objective image quality assessment.

Extrapolation of pre-screening trends: Impact of assumptions on overdiagnosis estimates by mammographic screening.

BACKGROUND: Overdiagnosis by mammographic screening is defined as the excess in breast cancer incidence in the presence of screening compared to the incidence in the absence of screening. The latter is often estimated by extrapolating the pre-screening incidence trend. The aim of this theoretical study is to investigate the impact of assumptions in extrapolating the pre-screening incidence trend of invasive breast cancer on the estimated percentage of overdiagnosis. METHODS: We extracted data on invasive breast cancer incidence and person-years by calendar year (1975-2009) and 5-year age groups (0-85 years) from Dutch databases. Different combinations of assumptions for extrapolating the pre-screening period were investigated, such as variations in the type of regression model, end of the pre-screening period, screened age range, post-screening age range and adjustment for a trend in women <45. This resulted in 69,120 estimates of the percentage of overdiagnosis, i.e. excess cancer incidence in the presence of screening as a proportion of the number of screen-detected and interval cancers. RESULTS: Most overdiagnosis percentages are overestimated because of inadequate adjustment for lead time. The overdiagnosis estimates range between -7.1% and 65.1%, with a median of 33.6%. The choice of pre-screening period has the largest influence on the estimated percentage of overdiagnosis: the median estimate is 17.1% for extrapolations using 1975-1986 as the pre-screening period and 44.7% for extrapolations using 1975-1988 as the pre-screening period. CONCLUSION: The results of this theoretical study most likely cover the true overdiagnosis estimate, which is unknown, and may not necessarily represent the median overdiagnosis estimate. This study shows that overdiagnosis estimates heavily depend on the assumptions made in extrapolating the incidence in the pre-screening period, especially on the choice of the pre-screening period. These limitations should be acknowledged when adopting this approach to estimate overdiagnosis.

Can the non-pre-whitening model observer, including aspects of the human visual system, predict human observer performance in mammography?

PURPOSE: In mammography, images are processed prior to display. Current methodologies based on physical image quality measurements are however not designed for the evaluation of processed images. Model observers (MO) might be suitable for this evaluation. The aim of this study was to investigate whether the non-pre-whitening (NPW) MO can be used to predict human observer performance in mammography-like images by including different aspects of the human visual system (HVS). METHODS: The correlation between human and NPW MO performance has been investigated for the detection of disk shaped objects in simulated white noise (WN) and clustered lumpy backgrounds (CLB), representing quantum noise limited and mammography-like images respectively. The images were scored by the MO and five human observers in a 2-alternative forced choice experiment. RESULTS: For WN images it was found that the log likelihood ratio (RLR2), which expresses the goodness of fit, was highest (0.44) for the NPW MO without addition of HVS aspects. For CLB the RLR2 improved from 0.46 to 0.65 with addition of HVS aspects. The correlation was affected by object size and background. CONCLUSIONS: This study shows that by including aspects of the HVS, the performance of the NPW MO can be improved to better predict human observer performance. This demonstrates that the NPW MO has potential for image quality assessment. However, due to the dependencies found in the correlation, the NPW MO can only be used for image quality assessment for a limited range of object sizes and background variability.

SIMULATING LOCAL DENSE AREAS USING PMMA TO ASSESS AUTOMATIC EXPOSURE CONTROL IN DIGITAL MAMMOGRAPHY.

Current digital mammography (DM) X-ray systems are equipped with advanced automatic exposure control (AEC) systems, which determine the exposure factors depending on breast composition. In the supplement of the European guidelines for quality assurance in breast cancer screening and diagnosis, a phantom-based test is included to evaluate the AEC response to local dense areas in terms of signal-to-noise ratio (SNR). This study evaluates the proposed test in terms of SNR and dose for four DM systems. The glandular fraction represented by the local dense area was assessed by analytic calculations. It was found that the proposed test simulates adipose to fully glandular breast compositions in attenuation. The doses associated with the phantoms were found to match well with the patient dose distribution. In conclusion, after some small adaptations, the test is valuable for the assessment of the AEC performance in terms of both SNR and dose.