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.

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.

Inter-observer variability in mammography screening and effect of type and number of readers on screening outcome.

We prospectively determined the variability in radiologists' interpretation of screening mammograms and assessed the influence of type and number of readers on screening outcome. Twenty-one screening mammography radiographers and eight screening radiologists participated. A total of 106,093 screening mammograms were double-read by two radiographers and, in turn, by two radiologists. Initially, radiologists were blinded to the referral opinion of the radiographers. A woman was referred if she was considered positive at radiologist double-reading with consensus interpretation or referred after radiologist review of positive cases at radiographer double-reading. During 2-year follow-up, clinical data, breast imaging reports, biopsy results and breast surgery reports were collected of all women with a positive screening result from any reader. Single radiologist reading (I) resulted in a mean cancer detection rate of 4.64 per 1000 screens (95% confidence intervals (CI)=4.23-5.05) with individual variations from 3.44 (95% CI=2.30-4.58) to 5.04 (95% CI=3.81-6.27), and a sensitivity of 63.9% (95% CI=60.5-67.3), ranging from 51.5% (95% CI=39.6-63.3) to 75.0% (95% CI=65.3-84.7). Sensitivity at non-blinded, radiologist double-reading (II), radiologist double-reading followed by radiologist review of positive cases at radiographer double-reading (III), triple reading by one radiologist and two radiographers with referral of all positive readings (IV) and quadruple reading by two radiologists and two radiographers with referral of all positive readings (V) were as follows: 68.6% (95% CI=65.3-71.9) (II); 73.2% (95% CI=70.1-76.4) (III); 75.2% (95% CI=72.1-78.2) (IV), and 76.9% (95% CI=73.9-79.9) (V). We conclude that screener performance significantly varied at single-reading. Double-reading increased sensitivity by a relative 7.3%. When there is a shortage of screening radiologists, triple reading by one radiologist and two radiographers may replace radiologist double-reading.

Breast cancer after a negative screen: follow-up of women participating in the DOM Screening Programme.

First-round screening results for women participating in the DOM project (a screening programme for early detection of breast cancer) are described for the age groups 40-49 and 50-64 at entry. In the younger age group, a low pick-up rate (1.96 per 1000) in proportion to the expected incidence rate in the absence of screening (1.46 per 1000) was found. For the older age group, these rates were 4.25 and 2.03, respectively, per 1000. Interval cancers occurred (relatively) more frequently in younger women. After 2 years the ratio between interval-cancers and screen-detected tumours was about 1:1 in the younger age group and 1:2.5 in the older age group. These different results can be caused by too low a sensitivity of mammography and/or a higher tumour growth rate at a young age. The sensitivity of the screen at various periods of follow-up, was compared: a rapidly decreasing sensitivity of mammography was seen for women under the age of 50, in contrast to a slower decrease for women over this age. This rapid decrease may be caused by a relatively high tumour growth rate in younger women.

Evaluation of a breast cancer screening programme--the DOM project.

In several studies it has been shown that breast cancer screening by means of mammography reduces breast cancer mortality. To ensure that when organising a service screening programme the aim is reached, it is necessary to control and monitor the process. This is possible by several methods. In this study, disease-free intervals and survival rates were used as monitoring tools. The DOM project, a breast cancer screening programme for women aged 50-64 years old at intake, started at the end of 1974. All breast cancer cases diagnosed between 1973 and 1989 were followed up to 1991. It is clear that disease-free interval and survival rates are proper predictors of the effects of screening on breast cancer mortality.

Hypertension and breast cancer risk in a 19-year follow-up study (the DOM cohort). Diagnostic investigation into mammarian cancer.

BACKGROUND: To investigate whether hypertension and the use of anti-hypertensive drugs are associated with breast cancer risk. METHODS: This was a prospective study of 11, 011 women living in Utrecht, the Netherlands, aged 50-65 years at enrolment in a breast cancer screening project (DOM cohort). Women attended screening rounds between 1974 and 1985 at which blood pressure was measured and information on drug use and breast cancer risk factors was ascertained. Since 1974 (median follow-up time 19 years), information on breast cancer occurrence and death has been registered. Hypertension was defined as a systolic blood pressure > 160 mmHg or a diastolic blood pressure > 95 mmHg or current use of drugs for the indication hypertension. Cox's regression analysis was used to investigate the association between hypertension (treated or untreated) and subsequent breast cancer risk. Analyses were adjusted for age, body mass index, height, parity, familial breast cancer, smoking and oral contraceptive use. RESULTS: A total of 523 women were diagnosed with breast cancer. Hypertensive women experienced a statistically significant increased breast cancer risk of 23% (age-adjusted hazard ratio (HRa) = 1.23; 95% confidence interval (CI) 1.01 -1.49). After adjustment for all confounders, the increase was 14% (HR = 1.14; 95% CI 0.93-1.40). The decline in risk was mainly attributable to the effect of BMI. The risk was similar in treated (HR = 1.22; 95% CI 0.91-1.63) and untreated hypertensive women (HR = 1.13; 95% CI 0.91-1.40). CONCLUSION: These results do not support an association between hypertension and breast cancer, and if there is a link, it is likely to be positive and relatively small in size (+14%). This relation, if present, is not attributable to anti-hypertensive drugs, since the relation is also present in non-drug users.

Breast cancer screening programmes in 22 countries: current policies, administration and guidelines. International Breast Cancer Screening Network (IBSN) and the European Network of Pilot Projects for Breast Cancer Screening.

BACKGROUND: Currently there are at least 22 countries worldwide where national, regional or pilot population-based breast cancer screening programmes have been established. A collaborative effort has been undertaken by the International Breast Cancer Screening Network (IBSN), an international voluntary collaborative effort administered from the National Cancer Institute in the US for the purposes of producing international data on the policies, funding and administration, and results of population-based breast cancer screening. METHODS: Two surveys conducted by the IBSN in 1990 and 1995 describe the status of population-based breast cancer screening in countries which had or planned to establish breast cancer screening programmes in their countries. The 1990 survey was sent to ten countries in the IBSN and was completed by nine countries. The 1995 survey was sent to and completed by the 13 countries in the organization at that time and an additional nine countries in the European Network. RESULTS: The programmes vary in how they have been organized and have changed from 1990 to 1995. The most notable change is the increase in the number of countries that have established or plan to establish organized breast cancer screening programmes. A second major change is in guidelines for the lower age limit for mammography screening and the use of the clinical breast examination and breast self-examination as additional detection methods. CONCLUSION: As high quality population-based breast cancer screening programmes are implemented in more countries, they will offer an unprecedented opportunity to assess the level of coverage of the population for initial and repeat screening, evaluation of performance, and, in the longer term, outcome of screening in terms of reduction in the incidence of late-stage disease and in mortality.

Reporting of performance indicators of mammography screening in Europe.

We compared short-term indicators for service mammography screening in Europe. Data were available from 17 programmes, although not all programmes provided a comprehensive reporting. More than 90% of the target population had been screened within the last 3 years in the WE trial, whereas only two-thirds of women in England and Copenhagen had been screened within the last 3 years, which will delay or reduce the effect of screening compared with the trial. Participation was highest in sparsely populated areas. Detection rates at first screen reached three times the baseline in Copenhagen, the Netherlands and North-West England. The clinical characteristics of screen-detected cases were badly reported. Given their importance for the long-term effect of screening, further data are warranted. Sensitivity and specificity could be measured only indirectly; they showed, however, considerable variation between programmes. Fyn, Florence and Stockholm had succeeded in combining high specificity with high sensitivity. With different recall policies, different proportions of women will experience a false-positive test; expected numbers after three screens were 14%, 10% and 1%, for England, Copenhagen and the Netherlands, respectively. Based on the observed wide variation in short-term indicators, a similar wide variation is expected in the effect of screening on breast cancer mortality.

Breast cancer screening in 21 countries: delivery of services, notification of results and outcomes ascertainment.

Following clinical trial evidence of mammography screening's efficacy and effectiveness, data are needed from organized population-based programmes to determine whether screening in these programmes results in breast cancer mortality reductions comparable to those demonstrated in controlled settings. The International Breast Cancer Screening Network (IBSN) conducted two international programme assessments: in 1990 among nine countries and in 1995 among 22 countries, obtaining information on the organization and process for screening within breast cancer screening programmes. This manuscript describes procedures for recruitment, service delivery, interpretation and communication of results, case ascertainment, and quality assurance. Practices in more established programmes are compared with pilot programmes. Each IBSN country defined a unique programme of population-based breast cancer screening. Some programmes were sub-national rather than national in scope, while others were in pilot stages of development. Screening took place in dedicated centres in established programmes and in both dedicated and general radiology centres in pilot programmes. Although most countries used personal invitation systems to recruit women to screening, other recruitment mechanisms were used. Most countries used two-view mammography in their screening programmes. About half had implemented independent double reading of mammograms, considering it a key component of high-quality mammography screening. In conclusion, diversity exists in the organization and delivery of screening mammography internationally. Quality assurance activities are a priority and are being evaluated in the IBSN.

Nationwide breast cancer screening programme fully implemented in The Netherlands.

The period 1990-1997 saw the implementation of a nationwide breast cancer screening programme in the Netherlands, which provided biennial mammography for all women aged 50-69 years (50-75 years at present). The National Evaluation Team monitors the programme annually collecting regional data on screening outcomes; regional cancer registries provide data on interval cancers and on breast cancers in unscreened women by linkage of cancer registry data to data on screened women. Of 4 million women invited, 78.5% attended for screening. Screening resulted in 13.1 referrals, 9.2 biopsies and 6.1 breast cancers detected per 1000 women screened initially (6.9, 4.5 and 3.5 per 1000 in subsequently screened women, respectively). Within the first 2 years following screening 0.95 interval cancers per 1000 women-years were diagnosed. The stage distribution of screen-detected cancers was more favourable than that of interval cancers and of those diagnosed in unscreened women. The results are largely consistent with expectations. Results may nonetheless be further improved, particularly the detection rate in subsequent screens.

International comparison of performance measures for screening mammography: can it be done?

OBJECTIVE: Published screening mammography performance measures vary across countries. An inter-national study was undertaken to assess the comparability of two performance measures: the recall rate and positive predictive value (PPV). These measures were selected because they do not require identification of all cancers in the screening population, which is not always possible. SETTING: The screening mammography programs or data registries in 25 member countries of the International Breast Cancer Screening Network (IBSN). METHODS: In 1999 an assessment form was distributed to IBSN country representatives in order to obtain information on how screening mammography was performed and what specific data related to recall rates and PPV were collected. Participating countries were then asked to provide data to allow calculation of recall rates, PPV and cancer detection rates for screening mammography by age group for women screened in the period 1997-1999. RESULTS: Twenty-two countries completed the assessment form and 14 countries provided performance data. Differences in screening mammography delivery and data collection were evident. For most countries, recall rates were higher for initial than for subsequent mammograms. There was no consistent relationship of initial to subsequent PPV, although PPV generally decreased as the recall rate increased. Recall rates decreased with increasing age, while PPV increased as age increased. CONCLUSION: Similar patterns for mammography performance measures were evident across countries.However, the development of a more standardized approach to defining and collecting data would allow more valid international comparisons, with the potential to optimize mammography performance. At present, international comparisons of performance should be made with caution due to differences in defining and collecting mammography data.

Carbon dioxide and water vapor exchange by young and old ponderosa pine ecosystems during a dry summer.

We investigated key factors controlling mass and energy exchange by a young (6-year-old) ponderosa pine (Pinus ponderosa Laws.) plantation on the west side of the Sierra Nevada Mountains and an old-growth ponderosa pine forest (mix of 45- and 250-year-old trees) on the east side of the Cascade Mountains, from June through September 1997. At both sites, we operated eddy covariance systems above the canopy to measure net ecosystem exchange of carbon dioxide and water vapor, and made concurrent meteorological and ecophysiological measurements. Our objective was to understand and compare the controls on ecosystem processes in these two forests. Precipitation is much higher in the young plantation than in the old-growth forest (1660 versus 550 mm year-1), although both forests experienced decreasing soil water availability and increasing vapor pressure deficits (D) as the summer of 1997 progressed. As a result, drought stress increased at both sites during this period, and changes in D strongly influenced ecosystem conductance and net carbon uptake. Ecosystem conductance for a given D was higher in the young pine plantation than in the old-growth forest, but decreased dramatically following several days of high D in late summer, possibly because of xylem cavitation. Net CO2 exchange generally decreased with conductance at both sites, although values were roughly twice as high at the young site. Simulations with the 3-PG model, which included the effect of tree age on fluxes, suggest that, during the fall through spring period, milder temperatures and ample water availability at the young site provide better conditions for photosynthesis than at the old pine site. Thus, over the long-term, the young site can carry more leaf area, and the climatic conditions between fall and spring offset the more severe limitations imposed by summer drought.

[The scientific basis for population screening for breast cancer in the Netherlands]. / De wetenschappelijke basis van het bevolkingsonderzoek naar borstkanker in Nederland.

A recent Cochrane review stated that there was a lack of evidence for a decrease in mortality as a result of population breast-cancer screening. The principal data were drawn from five Swedish randomized controlled trials and one Canadian trial. However, the studies cannot be so easily combined because there were important differences in the attendance rate, detection rate, technical quality, referral rate, clinical baseline situation and screening interval. For example, in one of the studies the women from the control arm underwent an annual clinical palpation carried out by a trained nurse or physician, which could have led to an underestimation of the screening effect. Further breast-cancer mortality might not be a good outcome measure because this was not reliably determined; only total mortality was to be observed. This is clinically and methodologically incorrect because breast-cancer mortality was meticulously studied, documented and validated. In the Cochrane review it is suggested that the randomisation was inadequate, but evidence for this was not supplied. The discussion about age differences as a marker for incorrect randomisation is out of date and has been revealed to be unjust. It seems likely that an important part of the decreasing trend in breast-cancer mortality in several countries (including the Netherlands) is due to screening programmes. However, the evaluation of breast-cancer mortality over the next five years is crucial, if greater certainty is to be gained about this.

Generalisability of the results of the Dutch-Belgian randomised controlled lung cancer CT screening trial (NELSON): does self-selection play a role?

The degree of self-selection in the Dutch-Belgian randomised controlled lung cancer screening trial (NELSON) was determined to assess the generalisability of the study results. 335,441 (mainly) men born in 1928-1953 received a questionnaire. Of the respondents (32%), eligible subjects were invited to participate (19%). Fifty-five percent gave informed consent and was randomised. Background characteristics were compared between male respondents on the first questionnaire (n = 92,802), eligible subjects among them (n = 18,570) and those randomised (n = 10,627) and Statistics Netherlands 2002-2005 (SN) (n = 5289) or GLOBE study-data (Dutch cohort) (n = 696). Initial respondents were less likely to be highly educated (OR(adj) = 0.84; 95% CI: 0.74-0.96) and comprised of significantly less current smokers (OR(adj) = 0.65; 95% CI: 0.61-0.69) compared to the general population. These current smokers smoked more heavily (OR(adj) = 1.23; 95% CI: 1.10-1.37), but for a shorter time-period (respondents: 31, SN: 42 years, p < 0.001). Age, general health, BMI, alcohol use and cancer prevalence were comparable. The randomised population was younger (Age 50-65) (randomised subjects: 85.3%, SN: 72% (p < 0.01)) comprised of more heavy current smokers (OR = 2.08; 95% CI: 1.75-2.44), that smoked for a shorter period of time (randomised subjects: 37, SN_selection: 42 years (p < 0.001)). Both the respondents (32%) of the first questionnaire as well as the randomised population of the NELSON trial appeared to differ slightly on smoking characteristics, but the differences were limited and probably balance each other. Results of the NELSON trial will be roughly applicable to the Dutch and probably other populations that fulfil our selection criteria.

False-positive results in mammographic screening for breast cancer in Europe: a literature review and survey of service screening programmes.

OBJECTIVE: To estimate the cumulative risk of a false-positive screening result in European mammographic screening programmes, and examine the rates and procedures of further assessment. METHODS: A literature review was conducted to identify studies of the cumulative risk of a false-positive result in European screening programmes (390,000 women). We then examined aggregate data, cross-sectional information about further assessment procedures among women with positive results in 20 mammographic screening programmes from 17 countries (1.7 million initial screens, 5.9 million subsequent screens), collected by the European Network for Information on Cancer project (EUNICE). RESULTS: The estimated cumulative risk of a false-positive screening result in women aged 50-69 undergoing 10 biennial screening tests varied from 8% to 21% in the three studies examined (pooled estimate 19.7%). The cumulative risk of an invasive procedure with benign outcome ranged from 1.8% to 6.3% (pooled estimate 2.9%). The risk of undergoing surgical intervention with benign outcome was 0.9% (one study only). From the EUNICE project, the proportions of all screening examinations in the programmes resulting in needle biopsy were 2.2% and 1.1% for initial and subsequent screens, respectively, though the rates differed between countries; the corresponding rates of surgical interventions among women without breast cancer were 0.19% and 0.07%. CONCLUSION: The specific investigative procedures following a recall should be considered when examining the cumulative risk of a false-positive screening result. Most women with a positive screening test undergo a non-invasive assessment procedure. Only a small proportion of recalled women undergo needle biopsy, and even fewer undergo surgical intervention.

Mammographic screening programmes in Europe: organization, coverage and participation.

OBJECTIVES: To summarize participation and coverage rates in population mammographic screening programmes for breast cancer in Europe. METHODS: We used the European Network for Information on Cancer (EUNICE), a web-based data warehouse (EUNICE Breast Cancer Screening Monitoring, EBCSM) for breast cancer screening, to obtain information on programme characteristics, coverage and participation from its initial application in 10 national and 16 regional programmes in 18 European countries. RESULTS: The total population targeted by the screening programme services covered in the report comprised 26.9 million women predominantly aged 50-69. Most of the collected data relates to 2005, 2006 and/or 2007. The average participation rate across all programmes was 53.4% (range 19.4-88.9% of personally invited); or 66.4% excluding Poland, a large programme that initiated personal invitations in 2007. Thirteen of the 26 programmes achieved the European Union benchmark of acceptable participation (>70%), nine achieved the desirable level (>75%). Despite considerable invitation coverage across all programmes (79.3%, range 50.9-115.2%) only 48.2% (range 28.4-92.1%) of the target population were actually screened. The overall invitation and examination coverage excluding Poland was 70.9% and 50.3%, respectively. CONCLUSIONS: The results demonstrate the feasibility of European-wide screening monitoring using the EBCSM data warehouse, although further efforts to refine the system and to harmonize standards and data collection practices will be required, to fully integrate all European countries. The more than three-fold difference in the examination coverage should be taken into account in the evaluation of service screening programmes.

Impact of a programme of mass mammography screening for breast cancer on socio-economic variation in survival: a population-based study.

BACKGROUND: After a systematic mass mammography breast cancer screening programme was implemented between 1991 and 1996 (attendance 80%), we evaluated its impact on survival according to socioeconomic status (SES). METHODS: We studied survival rates up to 1-1-2005 for all consecutive breast cancer patients aged 50-69 and diagnosed in the period 1983-2002 in the area of the Eindhoven Cancer Registry (n = 4939). Multivariate analyses were performed using Cox regression analysis. RESULTS: The proportion of breast cancer patients with a low SES decreased from 22% in 1983-1990 to 14% in 1997-2002 when attendance was 85%. The proportion of newly diagnosed patients with stage III or IV disease in 1997-2002 was only 10% compared to 14% in 1991-1996 and 26% in 1983-1989 (P < 0.0001). Stage distribution improved for all socio-economic groups (P = 0.01). Survival was similar for all socio-economic groups in 1983-1990, but after the introduction of the screening programme women with low SES had lower age- and stage-adjusted survival rates (HR 2.0, 95%CI: 1.3-3.0). Survival was better for patients diagnosed in 1997-2002 compared to 1983-1990 for all socioeconomic strata; it was substantially better for the high SES group (HR 0.36, 0.2-0.5) compared to the lowest SES (HR 0.77, 0.6-1.1). CONCLUSION: Although survival improved for women from each of the socio-economic strata, related to the high participation rate of the screening programme, women from lower socio-economic strata clearly benefited less from the breast cancer screening programme. That is also related to the higher prevalence of comorbidity and possibly suboptimal treatment.

Cost-effectiveness of different reading and referral strategies in mammography screening in the Netherlands.

In mammography screening with double reading, different strategies can be used when the readers give discordant recommendations for referral. We investigated whether the results of the Dutch breast cancer screening programme can be optimised by replacing the standard referral strategy by consensus. Twenty-six screening radiologists independently and blinded to outcome read a test set consisting of previous screening mammograms of 250 cases (screen-detected and interval cancers) and 250 controls. Their referral recommendations were paired and, in case of discrepancy, re-read according to three referral strategies: (1) decision by one of the readers; (2) arbitration by a third reader; (3) referral if both readers agree (consensus). Data allowed studying other referral strategies, including referral if any reader suggests, as well. Double reading with referral if any reader suggests resulted in a 1.03 times higher sensitivity (76.6%) and a 1.31 times higher referral rate (1.26%) than double reading with consensus. To estimate the cost-effectiveness, the outcomes were used in a microsimulation model. Even if double reading with referral if any reader suggests results in four times as high referral rates and an accompanying increase of biopsies or other invasive procedures, the cost-effectiveness of 4,190 Euros per life-year gained may well be in the range of acceptable cost-effectiveness for Dutch health care programmes.