Incidence of advanced-stage breast cancer in regular participants of a mammography screening program: a prospective register-based study.

BACKGROUND: The European Guidelines for breast cancer screening suggest that the impact of population-based mammography screening programmes (MSP) may be assessed using the relative reduction in the incidence of advanced breast cancer (ABC, that is, stage UICC II and higher) as a surrogate indicator of screening effectiveness. METHODS: This prospective, population register-based study contained individual data of 1,200,246 women (aged 50-69 years) who attended the initial prevalence screening between 2005 and 2009. Of them, 498,029 women returned for the regular (i.e., within 24 months) first subsequent, and 208,561 for the regular second subsequent incidence screenings. The incidence rate of ABC was calculated for the 24-months period following, but not including, the initial screening by incorporating all interval ABCs and all ABCs detected at the regular first incidence screening; the ABC rate for the second 24-months period was determined in the same way, including ABCs detected in the interval after the first and, respectively, at the second incidence screening. The relative reduction in the ABC incidence was derived by comparing the age-standardized rates in these two periods with an age-standardized reference incidence rate, observed in the target population before the MSP implementation. The strengths and weaknesses of this particular study design were contrasted with a recently published checklist of main methodological problems affecting studies of the effect of MSP on ABC incidence. RESULTS: The age-standardized ABC incidence rate was 291.6 per 100,000 women for the 24-months period subsequent to the initial screening, and 275.0/100,000 for the 24-months period following the first subsequent screening. Compared to the 2-year incidence of 349.4/100,000 before the start of the MSP, this amounted to a relative reduction of 16.5 and 21.3%, respectively, in the incidence of ABC among regular MSP participants. CONCLUSIONS: The design employed in this study avoids some of the substantial methodological limitations that compromised previous observational studies. Nevertheless, specific limitations prevail that demand a cautious interpretation of the results. Therefore, the study findings, indicating a reduction in ABC for regular MSP participants, need to be followed with respect to potential impacts on breast cancer mortality rates.

Secure Linking of Data from Population-Based Cancer Registries with Healthcare Data to Evaluate Screening Programs.

BACKGROUND: The evaluation of population-based screening programs, like the German Mammography Screening Program (MSP), requires collection and linking data from population-based cancer registries and other sources of the healthcare system on a case- specific level. To link such sensitive data, we developed a method that is compliant with German data protection regulations and does not require written individual consent. METHODS: Our method combines a probabilistic record linkage on encrypted identifying data with 'blinded anonymisation'. It ensures that all data either are encrypted or have a defined and measurable degree of anonymity. The data sources use a software to transform plain-text identifying data into a set of irreversibly encrypted person cryptograms, while the evaluation attributes are aggregated in multiple stages and are reversibly encrypted. A pseudonymisation service encrypts the person cryptograms into record assignment numbers and a downstream data-collecting centre uses them to perform the probabilistic record linkage. The blinded anonymisation solves the problem of quasi-identifiers within the evaluation data. It allows selecting a specific set of the encrypted aggregations to produce data export with ensured k-anonymity, without any plain-text information. These data are finally transferred to an evaluation centre where they are decrypted and analysed. Our approach allows creating several such generalisations, with different resulting suppression rates allowing dynamic balance information depth with privacy protection and also highlights how this affects data analysability. RESULTS: German data protection authorities approved our concept for the evaluation of the impact of the German MSP on breast cancer mortality. We implemented a prototype and tested it with 1.5 million simulated records, containing realistically distributed identifying data, calculated different generalisations and the respective suppression rates. Here, we also discuss limitations for large data sets in the cancer registry domain, as well as approaches for further improvements like l-diversity and how to reduce the amount of manual post-processing. CONCLUSION: Our approach enables secure linking of data from population-based cancer registries and other sources of the healthcare system. Despite some limitations, it enables evaluation of the German MSP program and can be generalised to be applicable to other projects.

Trends in surgical treatment for breast cancer in Germany after the implementation of the mammography screening program.

In Germany, the nationwide population-based mammography screening program (MSP) was introduced in 2005 and is full-running since 2010. By 2014, incidence rates for invasive breast cancer were very similar to those of the pre-screening era. Therefore, the ongoing effect of the MSP on breast cancer surgery rates can now be investigated. We analyzed population-based breast-conserving (BCS) and mastectomy (MET) surgery rates (per 100,000) among women aged < 50, 50-69 (eligible for the MSP), and 70+ years among women with in situ and invasive breast cancer during 2005-2015. For invasive breast cancer, both BCS and MET rates slightly increased in the age group < 50 years (38.3 in 2005 vs 42.5 in 2015 and 15.7 vs 18.2, respectively). In contrast, MET rates considerably decreased among women aged 50-69 and 70+ years (92 vs 65.4 and 155.4 vs 122.1, respectively), while BCS rates increased in both age groups (210.6 vs 254.4 and 147.2 vs 187, respectively). For in situ breast cancer, MET rates slightly increased in all age groups. BCS rates slightly increased in women aged < 50, but nearly doubled for women aged 50-69 (26.9 vs 49.1) and markedly increased in the 70+ age group (11.5 vs 16.1). During and after the implementation of MSP, there was a strong shift towards BCS within the screening-eligible age group and for women aged 70+ . Women with invasive breast cancer in these age groups may profit from screening with a decline of MET rates in favor of BCS rates at the expense of higher surgery rates for in situ breast cancer.

Development and Prospective Randomized Evaluation of a Decision Aid for Prostate-specific Antigen-based Early Detection of Prostate Cancer in Men Aged Between 55 and 69Yr: The PSAInForm Trial.

For men interested in early detection of prostate cancer, the potential impact on decisional conflict of a decision aid with or without cost compensation for the prostate-specific antigen test will be investigated.

Higher Detection Rates of Biologically Aggressive Breast Cancers in Mammography Screening than in the Biennial Interval. / Höhere Detektionsraten biologisch aggressiver Mammakarzinome im Mammografie-Screening als im 2-jährigen Intervall.

PURPOSE: Assessment of age group-dependent detection rates of invasive breast cancers among participants in mammography screening including the interval, classified into immunohistochemical subtypes indicating the intrinsic tumor aggressiveness. MATERIALS UND METHODS: The target population comprises women aged 50 - 69 years. All invasive breast cancers diagnosed in one screening (sc) unit during the implementation phase 1/2006 - 12/2010 or identified by the cancer registry during the biennial interval (iv) were categorized based on hormonal-receptor status (HR) and Her2-expression (Her2) into the following subtypes: a) HR+ Her2-, b) HR+ Her2 +, c) HR- Her2 + or d) HR- Her2- (triple-negative); Her2 + and triple-negative types were defined as aggressive. The calculated detection rates (DR, ‰) were based on 53 375 sc-examinations and for the interval on 52 887 sc-negative examinations. RESULTS: The DRs of all subtypes were higher in screening versus the interval: (a) 4.95 ‰ (n = 264) vs. 1.00 ‰ (n = 53); b) 0.92 ‰ (n = 49) vs. 0.25 ‰ (n = 13); c) 0.36 ‰ (n = 19) vs. 0.06 ‰ (n = 3); d) 0.39 ‰ (n = 21) vs. 0.19 ‰ (n = 10). 77.4 ‰ (89/115) of all aggressive breast cancers including the following 2-year interval were diagnosed by screening. The sum of the DR of aggressive cancers was 1.67 ‰ in screening and 0.49 ‰ in the interval; the corresponding DRs for women aged 60 - 69 years [sc: 2.24 ‰ (51/22 814), iv: 0.58 ‰ (13/22 536)] were higher than among women aged 50 - 59 years [sc: 1.24 ‰ (38/30 561), iv: 0.43 ‰ (13/30 351)]. CONCLUSION: Screening has the potential for earlier diagnosis of aggressive tumor types as its detection rate is about three-fold higher compared to the interval. Within the target group, participants aged 60 - 69 years are at risk based on absolute numbers. They show a nearly two-fold higher detection rate of Her2-positive or triple-negative tumors compared to the age group 50 - 59 years. KEY POINTS: · Her2-positive and triple-negative detection rates are higher in screening than in the interval.. · 77 % of aggressive subtypes are diagnosed by screening, 23 % during the 2-year interval.. · The detection rate is highest among women aged 60 - 69 years in screening.. CITATION FORMAT: · Prange A, Bokhof B, Polzer P et al. Higher Detection Rates of Biologically Aggressive Breast Cancers in Mammography Screening than in the Biennial Interval. Fortschr Röntgenstr 2019; 191: 130 - 136.

[Enrichment of Claims Data with Official Causes of Death Using a Record Linkage with the Epidemiological Cancer Registry of North Rhine-Westphalia: Feasibility Study and Comparison of Procedures]. / Anreicherung eines GKV-Datensatzes mit amtlichen Todesursachen über einen Abgleich mit dem Epidemiologischen Krebsregister Nordrhein-Westfalen: Machbarkeitsstudie und Methodenvergleich.

BACKGROUND: Claims data of the statutory health insurance (SHI) are an important data source for the evaluation of cancer prevention programs. However, this source does not contain relevant information on cause of death. This study examined whether individual claims data can be enriched with data on the required cause of death using record linkage procedures with suitable external data sources. METHODS: In the German pharmacoepidemiologic research database (GePaRD) we identified a sample of 25,528 deceased female residents of North Rhine Westphalia (NRW) who, according to GePaRD information, died between 2006 and 2013. Date and cause of all deaths among inhabitants of NRW since 2005 were available in the epidemiological cancer registry of NRW. In cooperation with 2 SHI companies, we tried to match each individual of the sample with a case of death in NRW and the corresponding cause of death using a probabilistic and, alternatively, a deterministic linkage procedure. RESULTS: Of the study sample, 94.72% were successfully matched by the probabilistic and 93.36% by the deterministic method. CONCLUSIONS: The probabilistic and the deterministic record linkage approach produced comparably high matching rates. Cases without matches are probably due to errors occurring at the stage of personal data entry. Given the lower technical efforts, the deterministic approach appears to be the method of choice for the enrichment of claims data with cause of death information from suitable external data sources in Germany.

[Time trend in programme sensitivity within the German mammography screening programme in North Rhine-Westphalia and Lower Saxony]. / Zeitliche Entwicklung der Programmsensitivität des deutschen Mammographie-Screening-Programms in Nordrhein-Westfalen und Niedersachsen.

BACKGROUND: The programme sensitivity is a performance indicator for evaluating the quality of the mammography screening programme (MSP). OBJECTIVES: We analysed the development of the programme sensitivity over time in two federal states of Germany, North Rhine-Westphalia (NRW) and Lower Saxony (NDS). MATERIALS AND METHODS: Data from 2,717,801 (NRW) and 1,197,660 (NDS) screening examinations between 2006 and 2011 were linked with data of the State Cancer Registry NRW and the Epidemiological Cancer Registry NDS, respectively. Breast cancers (invasive and in situ) were either detected at screening or diagnosed within the 24-month interval after an inconspicuous screening result outside the programme. The crude and age-standardized programme sensitivity was calculated per calendar year. The German mammography screening office provided aggregated recall rates. RESULTS: The age-standardized programme sensitivity increased markedly for initial screening examinations from 2006 to 2011 from 75.0% (95% CI: 72.1-77.9) to 80.5% (95% CI: 78.5-82.5) in NRW, and from 74.9% (95% CI: 71.4-78.5) to 84.7% (95% CI: 81.1-88.3) in NDS. Concurrently, recall rates increased as well. For subsequent screening examinations, the programme sensitivity increased from 2008 to 2011 from 68.1% (95% CI: 63.1-73.1) to 71.9% (95% CI: 70.2-73.6) in NRW, and from 69.8% (95% CI: 64.2-75.4) to 74.9% (95% CI: 72.3-77.5) in NDS, whereas the recall rates remained relatively constant. CONCLUSIONS: In both federal states, the programme sensitivity increased over time. This increase, possibly indicating an improved quality of diagnosis within the MSP as a learning system, is discussed under consideration of the age distribution of screening participants and the recall rates.

Differences in Breast Cancer Characteristics by Mammography Screening Participation or Non-Participation.

BACKGROUND: The goal of the German Mammography Screening Program (MSP) is to enable the early detection and less intensive treatment of breast cancer. We compared tumor characteristics and prognostic markers in breast cancers that were detected by screening in the MSP, in the interval after a negative screening, or among non-participants in screening. METHODS: This retrospective series includes all of the 1531 cases of invasive and in situ breast cancer (DCIS, ductal carcinoma in situ) that were newly diagnosed in two certified breast care centers in Münster in the period 2006-2012 among women in the MSP target population. Complete information on the tumor characteristics, tumor biology, and primary surgical treatment were available for all cases. The mode of cancer detection was determined from the state cancer registry of North Rhine-Westphalia. Due to the retrospective design of this case series, there was no randomized allocation. RESULTS: The 874 cases of breast cancer among MSP participants (714 detected by screening, 160 in the interval after a negative screen) and the 657 cases among non-participants arose in women of similar age (mean, 60.2 versus 59.3 years). MSP participants with breast cancer had DCIS more commonly than non-participants did (23% versus 13%); invasive carcinomas were smaller (74% versus 55% in the T1 stage), less commonly node-positive (25% versus 31%), less commonly high-grade (19% versus 27%), and less commonly triple-negative (7% versus 12%); MSP participants received neoadjuvant treatment less frequently (2% versus 8%) and more frequently underwent breast-conserving surgery (75% versus 62%). They less commonly had a guideline-based indication for adjuvant chemotherapy (46% versus 52%). CONCLUSION: MSP participants with invasive breast cancer can generally be treated with less intensive surgical and systemic therapy than non-participants, even if interval cancers are also taken into account. Future studies should also investigate quality of life after a diagnosis of invasive carcinoma in screening participants.

Digital breast tomosynthesis plus synthesised images versus standard full-field digital mammography in population-based screening (TOSYMA): protocol of a randomised controlled trial.

INTRODUCTION: Development of digital breast tomosynthesis (DBT) provides a technology that generates three-dimensional data sets, thus reducing the pitfalls of overlapping breast tissue. Observational studies suggest that the combination of two-dimensional (2D) digital mammography and DBT increases diagnostic accuracy. However, because of duplicate exposure, this comes at the cost of an augmented radiation dose. This undesired adverse impact can be avoided by using synthesised 2D images reconstructed from the DBT data (s2D).We designed a diagnostic superiority trial on a high level of evidence with the aim of providing a comparison of screening efficacy parameters resulting from DBT+s2D versus the current screening standard 2D full-field digital mammography (FFDM) in a multicentre and multivendor setting on the basis of the quality-controlled, population-based, biennial mammography screening programme in Germany. METHODS AND ANALYSIS: 80 000 women in the eligible age 50-69 years attending the routine mammography screening programme and willing to participate in the TOSYMA trial will be assigned by 1:1 randomisation to either the intervention arm (DBT+s2D) or the control arm (FFDM) during a 12-month recruitment period in screening units of North Rhine-Westphalia and Lower Saxony. State cancer registries will provide the follow-up of interval cancers.Primary endpoints are the detection rate of invasive breast cancers at screening examination and the cumulative incidence of interval cancers in the 2 years after a negative examination. Secondary endpoints are the detection rate of ductal carcinoma in situ and of tumour size T1, the recall rate for assessment, the positive predictive value of recall and the cumulative 12-month incidence of interval cancers. An adaptive statistical design with one interim analysis provides the option to modify the design. ETHICS AND DISSEMINATION: This protocol has been approved by the local medical ethical committee (2016-132-f-S). Results will be submitted to international peer-reviewed journals. TRIAL REGISTRATION: NCT03377036; Pre-results.

Skin cancer rates in North Rhine-Westphalia, Germany before and after the introduction of the nationwide skin cancer screening program (2000-2015).

Germany is the first nation that implemented a nationwide skin cancer screening program in 2008. The aim is to study the effect of the program on skin cancer rates and to estimate the number needed to screen for an unselected and a hypothetical high-risk population in Germany. We used population-based data on skin cancer incidence (2000-2014), mortality, hospitalization and sick leave (2000-2015) from North Rhine-Westphalia, Germany (18 million population). We calculated annual age-standardized rates per 100,000 person years and calculated the relative change of the rates (%) including 95% confidence intervals (95% CI). Between 2007 and 2014, the estimated annual percentage change (EAPC) of the age-standardized incidence rate of skin melanoma was 3.8% among men and women. These increases were accompanied by increases of the age-standardized mortality rates (EAPC men 3.2%, women 2.0%) and age-standardized sick leave rates (EAPC men 11.0%, women 6.1%). Hospitalization rates showed barely any change. All types of rates for nonmelanoma skin cancer showed marked increases. The number needed to screen for skin melanoma death would be 34,000 if the risk reduction due to screening would be 50%. In a hypothetical high-risk approach with 10% of the population at high risk, that is, a relative risk of melanoma death of 4.0, a skin melanoma mortality risk reduction of 50% among these people due to screening would result in a reduction of the skin melanoma mortality by 15% in the total population. However, this reduction would require a number needed to screen of 11,141. Seven years after the introduction of the skin cancer screening program, there is no discernible beneficial effect at population level. The estimated number needed to screen for skin melanoma in an unselected approach is high and a realistic high-risk approach is currently not feasible.

Detection Rates of Ductal Carcinoma in Situ with Biennial Digital Mammography Screening: Radiologic Findings Support Pathologic Model of Tumor Progression.

Purpose To compare detection rates of ductal carcinoma in situ (DCIS), classified according to nuclear grade, between the prevalence round (baseline screening) and two subsequent screening rounds of a population-based digital mammography screening program, to assess differences over time. Materials and Methods The cancer registry provided data for 1970 graded pure DCIS cases from 16 screening regions of the prevalence round (baseline screening, from 2005 to 2008), first subsequent round, and second subsequent round; the interval between all screening rounds was 22-30 months. Age-adjusted logistic regression analysis was performed to compare the grade-specific detection rates between the prevalence round (reference) and subsequent screening rounds. Results Over all screening rounds, cancer detection rates were lowest for low-grade DCIS (range, 0.11 [58 of 508 817 patients] to 0.25 [178 of 713 867 patients] per 1000 women screened) and highest for high-grade DCIS (range, 0.53[271 of 508 817 patients] to 0.59 [237 of 398 944 patients] per 1000 women screened). Detection rates for low-grade DCIS were significantly lower in the first (odds ratio [OR] = 0.45, P < .001) and second (OR = 0.57, P < .001) subsequent screening rounds compared with that in the prevalence round; the relative reduction of detection rates of intermediate-grade DCIS was less pronounced (OR = 0.79, P = .006 and OR = 0.76, P = .003, respectively). Conversely, the detection rate of high-grade DCIS remained at the high level found in the prevalence screening (OR = 0.89, P = .143 and OR = 0.97, P = .700, respectively). Conclusion The findings demonstrate persistently high detection rates of high-grade DCIS in two consecutive subsequent screening rounds compared with the prevalence round; conversely, rates of low-grade DCIS and, less markedly, intermediate-grade DCIS decreased in subsequent rounds. Grade-related changes of DCIS detection are suggestive of distinct dynamics of lesion progression. © RSNA, 2017 An earlier incorrect version of this article appeared online. This article was corrected on November 10, 2017.

Trends in advanced breast cancer incidence rates after implementation of a mammography screening program in a German population.

BACKGROUND: Mammography screening programs (MSPs) aim to detect early-stage breast cancers in order to decrease the incidence of advanced-stage breast cancers and to reduce breast cancer mortality. We analyzed the time trends of advanced-stage breast cancer incidence rates in the target population before and after implementation of the MSP in a region of northwestern Germany. METHODS: The MSP in the Münster district started in October 2005. A total of 13,874 women with an incident invasive breast cancer (BC) was identified by the population-based epidemiological cancer registry between 2000 and 2013 in the target group 50-69 years. Multiple imputation methods were used to replace missing data on tumor stages (10.4%). The incidence rates for early-stage (UICC I) and advanced-stage (UICC II+) BC were determined, and Poisson regression analyses were performed to assess trends over time. RESULTS: The incidence rates for UICC I breast cancers increased during the step-up introduction of the MSP and remained elevated thereafter. By contrast, after increasing from 2006 to 2008, the incidence rates of UICC II+ breast cancers decreased to levels below the pre-screening period. Significantly decreasing UICC II+ incidence rates were limited to the age group 55-69 years and reached levels that were significantly lower than incidence rates in the pre-screening period. DISCUSSION: The incidence rates of advanced-stage breast cancers decreased in the age groups from 55 years to the upper age limit for screening eligibility, but not in the adjacent age groups. The findings are consistent with MSP lead time effects and seem to indicate that the MSP lowers advanced-stage breast cancer rates in the target population.

Digital Mammography Screening: Does Age Influence the Detection Rates of Low-, Intermediate-, and High-Grade Ductal Carcinoma in Situ?

PURPOSE: To investigate the association between age at screening and detection rates for ductal carcinoma in situ (DCIS) separately for different nuclear grades after introduction of a population-based digital mammography screening program. MATERIALS AND METHODS: The retrospective study was approved by the ethics board and did not require informed consent. In 733 905 women aged 50-69 years who participated in a screening program for the first time in 2005-2008 (baseline examinations were performed with digital mammography), DCIS detection rates were determined for 5-year age groups (detection rates per 1000 women screened) to distinguish high-, intermediate-, and low-grade DCIS. Multivariable logistic regression was used to compare detection rates between age groups by adjusting for screening units (P < .05). RESULTS: There were 989 graded DCIS diagnoses among 733 905 women (detection rate, 1.35‰): 419 diagnoses of high-grade DCIS (detection rate, 0.57‰), 388 diagnoses of intermediate-grade DCIS (detection rate, 0.53‰), and 182 diagnoses of low-grade DCIS (detection rate, 0.25‰). Detection rate for types of DCIS combined increased significantly across age groups (50-54 years, detection rate of 1.15‰ [254 of 220 985 women]; 55-59 years, detection rate of 1.23‰ [218 of 177 782 women]; 60-64 years, detection rate of 1.34‰ [201 of 150 415 women]; and 65-69 years, detection rate of 1.71‰ [316 of 184 723 women]; P < .001). Of note, the detection rate for high-grade DCIS showed a significant increase with age (odds ratio, 1.18 per 5-year age group; P < .0001). The increase was lower for intermediate-grade DCIS (odds ratio, 1.11; P = .016) and not significant for low-grade DCIS (P = .10). CONCLUSION: Total DCIS detection rates increase with age, mostly because of an increase in high- and intermediate-grade DCIS, which are precursor lesions that carry a higher risk for transition to more aggressive invasive breast cancer than low-grade DCIS.

Small-area spatio-temporal analyses of participation rates in the mammography screening program in the city of Dortmund (NW Germany).

BACKGROUND: The population-based mammography screening program (MSP) was implemented by the end of 2005 in Germany, and all women between 50 and 69 years are actively invited to a free biennial screening examination. However, despite the expected benefits, the overall participation rates range only between 50 and 55%. There is also increasing evidence that belonging to a vulnerable population, such as ethnic minorities or low income groups, is associated with a decreased likelihood of participating in screening programs. This study aimed to analyze in more detail the intra-urban variation of MSP uptake at the neighborhood level (i.e. statistical districts) for the city of Dortmund in northwest Germany and to identify demographic and socioeconomic risk factors that contribute to non-response to screening invitations. METHODS: The numbers of participants by statistical district were aggregated over the three periods 2007/2008, 2009/2010, and 2011/2012. Participation rates were calculated as numbers of participants per female resident population averaged over each 2-year period. Bayesian hierarchical spatial models extended with a temporal and spatio-temporal interaction effect were used to analyze the participation rates applying integrated nested Laplace approximations (INLA). The model included explanatory covariates taken from the atlas of social structure of Dortmund. RESULTS: Generally, participation rates rose for all districts over the time periods. However, participation was persistently lowest in the inner city of Dortmund. Multivariable regression analysis showed that migrant status and long-term unemployment were associated with significant increases of non-attendance in the MSP. CONCLUSION: Low income groups and immigrant populations are clustered in the inner city of Dortmund and the observed spatial pattern of persistently low participation in the city center is likely linked to the underlying socioeconomic gradient. This corresponds with the findings of the ecological regression analysis manifesting socioeconomically deprived neighborhoods as risk factors for low attendance in the MSP. Spatio-temporal surveillance of participation in cancer screening programs may be used to identify spatial inequalities in screening uptake and plan spatially focused interventions.

Blinded Anonymization: a method for evaluating cancer prevention programs under restrictive data protection regulations.

Evaluating cancer prevention programs requires collecting and linking data on a case specific level from multiple sources of the healthcare system. Therefore, one has to comply with data protection regulations which are restrictive in Germany and will likely become stricter in Europe in general. To facilitate the mortality evaluation of the German mammography screening program, with more than 10 Million eligible women, we developed a method that does not require written individual consent and is compliant to existing privacy regulations. Our setup is composed of different data owners, a data collection center (DCC) and an evaluation center (EC). Each data owner uses a dedicated software that preprocesses plain-text personal identifiers (IDAT) and plaintext evaluation data (EDAT) in such a way that only irreversibly encrypted record assignment numbers (RAN) and pre-aggregated, reversibly encrypted EDAT are transmitted to the DCC. The DCC uses the RANs to perform a probabilistic record linkage which is based on an established and evaluated algorithm. For potentially identifying attributes within the EDAT ('quasi-identifiers'), we developed a novel process, named 'blinded anonymization'. It allows selecting a specific generalization from the pre-processed and encrypted attribute aggregations, to create a new data set with assured k-anonymity, without using any plain-text information. The anonymized data is transferred to the EC where the EDAT is decrypted and used for evaluation. Our concept was approved by German data protection authorities. We implemented a prototype and tested it with more than 1.5 Million simulated records, containing realistically distributed IDAT. The core processes worked well with regard to performance parameters. We created different generalizations and calculated the respective suppression rates. We discuss modalities, implications and limitations for large data sets in the cancer registry domain, as well as approaches for further improvements like l-diversity and automatic computation of 'optimal' generalizations.

Comparing adaptive and fixed bandwidth-based kernel density estimates in spatial cancer epidemiology.

BACKGROUND: Monitoring spatial disease risk (e.g. identifying risk areas) is of great relevance in public health research, especially in cancer epidemiology. A common strategy uses case-control studies and estimates a spatial relative risk function (sRRF) via kernel density estimation (KDE). This study was set up to evaluate the sRRF estimation methods, comparing fixed with adaptive bandwidth-based KDE, and how they were able to detect 'risk areas' with case data from a population-based cancer registry. METHODS: The sRRF were estimated within a defined area, using locational information on incident cancer cases and on a spatial sample of controls, drawn from a high-resolution population grid recognized as underestimating the resident population in urban centers. The spatial extensions of these areas with underestimated resident population were quantified with population reference data and used in this study as 'true risk areas'. Sensitivity and specificity analyses were conducted by spatial overlay of the 'true risk areas' and the significant (α=.05) p-contour lines obtained from the sRRF. RESULTS: We observed that the fixed bandwidth-based sRRF was distinguished by a conservative behavior in identifying these urban 'risk areas', that is, a reduced sensitivity but increased specificity due to oversmoothing as compared to the adaptive risk estimator. In contrast, the latter appeared more competitive through variance stabilization, resulting in a higher sensitivity, while the specificity was equal as compared to the fixed risk estimator. Halving the originally determined bandwidths led to a simultaneous improvement of sensitivity and specificity of the adaptive sRRF, while the specificity was reduced for the fixed estimator. CONCLUSION: The fixed risk estimator contrasts with an oversmoothing tendency in urban areas, while overestimating the risk in rural areas. The use of an adaptive bandwidth regime attenuated this pattern, but led in general to a higher false positive rate, because, in our study design, the majority of true risk areas were located in urban areas. However, there is a strong need for further optimizing the bandwidth selection methods, especially for the adaptive sRRF.

Digital mammography screening in Germany: Impact of age and histological subtype on program sensitivity.

INTRODUCTION: Program sensitivity (PS), i.e., the ratio of screen-detected cancers divided by the sum of screen-detected plus interval cancers, is a major outcome in population-based mammography screening programs (MSP). This study evaluated PS within the digital MSP in Germany focussing on the impact of age and histological subtype. METHODS: Data of 838,579 first-time participants aged 50-69 years who were screened in 2005-2008 were linked with cancer registry data from Germany's most populous state, North Rhine-Westphalia. Invasive breast cancers and ductal carcinomas in situ (DCIS) were detected either at screening or during the 24 month post-screening interval. PS was evaluated with respect to age at screening, in-situ or invasive cancer and histological characteristics. RESULTS: In total, 6767 cancers were detected at screening and 1884 cancers were diagnosed during the post-screening interval. The overall PS amounted to 78.2% and increased from 72.1% at age 50-54 years to 82.4% at age 65-69 years (p for trend <0.0001). PS was higher for non-lobular (79.1%) than lobular carcinomas (72.1%, p < 0.0001). The highest PS was observed in DCIS across all ages (>90%), while PS was lowest among participants aged 50-54 years with invasive breast cancer (67.7%), particularly among those with lobular subtype (62.8%). Interval cancers showed generally more advanced tumour stages. CONCLUSIONS: While overall PS was high, differences across subgroups indicated that youngest screening participants are at higher risk of interval cancer. Age-adapted recall and assessment strategies in younger participants may need to be considered to improve PS in younger women.

Digital mammography screening: association between detection rate and nuclear grade of ductal carcinoma in situ.

PURPOSE: To determine the relationship between overall detection rates of ductal carcinoma in situ (DCIS) and the specific detection rates of low-, intermediate-, and high-grade DCIS at the start of a digital mammography screening program. MATERIALS AND METHODS: The study was approved by the local ethics board and did not require informed consent. Data were included of the first round of digital mammography examinations, performed in 17 screening units in women aged 50-69 years from 2005 to 2008. Grading was provided by the cancer registry for 1018 DCIS cases. The association between the overall cancer detection rate (cases per 100 women screened) and the separate cancer detection rate for invasive cancers and for DCIS was assessed. Likewise, the total DCIS cancer detection rate was separated into rates for low, intermediate, and high grades. Spearman rank correlations were used for analysis. RESULTS: The overall cancer detection rate correlated with both the cancer detection rate of invasive cancers and the cancer detection rate of DCIS (r = 0.96 and r = 0.88, respectively; P < .001 for both). The cancer detection rate of total DCIS with grading varied among screening units (range, 0.05-0.25), it was borderline not significantly correlated with the cancer detection rate of low-grade DCIS (range, 0.004-0.05; r = 0.49; P = .052), and it showed significant correlations with higher cancer detection rate of intermediate-grade DCIS (range, 0.02-0.12; r = 0.89; P < .001) and of high-grade DCIS (range, 0.03-0.11; r = 0.88; P < .001). CONCLUSION: This study demonstrates that high overall cancer detection rates in digital mammography screening are related to high detection rates of invasive cancers, as well as DCIS. Increases in the detection rates of DCIS were not driven by disproportionate increments of the slowly progressive low-grade subtype but rather by increased rates of intermediate- and high-grade subtypes that carry a higher risk of transition to invasive cancers.

Detecting cancer clusters in a regional population with local cluster tests and Bayesian smoothing methods: a simulation study.

BACKGROUND: There is a rising public and political demand for prospective cancer cluster monitoring. But there is little empirical evidence on the performance of established cluster detection tests under conditions of small and heterogeneous sample sizes and varying spatial scales, such as are the case for most existing population-based cancer registries. Therefore this simulation study aims to evaluate different cluster detection methods, implemented in the open source environment R, in their ability to identify clusters of lung cancer using real-life data from an epidemiological cancer registry in Germany. METHODS: Risk surfaces were constructed with two different spatial cluster types, representing a relative risk of RR = 2.0 or of RR = 4.0, in relation to the overall background incidence of lung cancer, separately for men and women. Lung cancer cases were sampled from this risk surface as geocodes using an inhomogeneous Poisson process. The realisations of the cancer cases were analysed within small spatial (census tracts, N = 1983) and within aggregated large spatial scales (communities, N = 78). Subsequently, they were submitted to the cluster detection methods. The test accuracy for cluster location was determined in terms of detection rates (DR), false-positive (FP) rates and positive predictive values. The Bayesian smoothing models were evaluated using ROC curves. RESULTS: With moderate risk increase (RR = 2.0), local cluster tests showed better DR (for both spatial aggregation scales > 0.90) and lower FP rates (both < 0.05) than the Bayesian smoothing methods. When the cluster RR was raised four-fold, the local cluster tests showed better DR with lower FPs only for the small spatial scale. At a large spatial scale, the Bayesian smoothing methods, especially those implementing a spatial neighbourhood, showed a substantially lower FP rate than the cluster tests. However, the risk increases at this scale were mostly diluted by data aggregation. CONCLUSION: High resolution spatial scales seem more appropriate as data base for cancer cluster testing and monitoring than the commonly used aggregated scales. We suggest the development of a two-stage approach that combines methods with high detection rates as a first-line screening with methods of higher predictive ability at the second stage.