Impact of mammographic screening and advanced cancer definition on the percentage of advanced-stage cancers in a steady-state breast screening programme in the Netherlands.

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

Effect of screening mammography on breast cancer mortality: Quasi-experimental evidence from rollout of the Dutch population-based program with 17-year follow-up of a cohort.

There is uncertainty about the magnitude of the effect of screening mammography on breast cancer mortality. The relevance and validity of evidence from dated randomized controlled trials has been questioned, whereas observational studies often lack a valid comparison group. There is no estimate of the effect of one screening invitation only. We exploited the geographic rollout of the Dutch screening mammography program across municipalities to estimate the effects of one additional biennial screening invitation on breast cancer and all-cause mortality. Population administrative data provided vital status and cause of death of a cohort of women aged 49-63 in 1995 over 17 years. Linear probability models were used to estimate the mortality effects. We estimated 154 fewer breast cancer deaths (95% confidence interval: 40-267; p = 0.01) over 17 years in a population of 100,000 women aged 49-63 who received one additional biennial screening invitation, which corresponds to an 9.6% risk reduction for a woman of age 56. The estimated effect on all-cause mortality was negative but not close to statistical significance. Our study shows that one single invitation for breast cancer screening is effective in reducing breast cancer mortality, which is important for health policy. The effect is smaller than previous estimates of the effect of invitation for multiple screens, which further emphasizes the importance of achieving regular participation.

Detection and interval cancer rates during the transition from screen-film to digital mammography in population-based screening.

BACKGROUND: Between 2003 and 2010 digital mammography (DM) gradually replaced screen-film mammography (SFM) in the Dutch breast cancer screening programme (BCSP). Previous studies showed increases in detection rate (DR) after the transition to DM. However, national interval cancer rates (ICR) have not yet been reported. METHODS: We assessed programme sensitivity and specificity during the transition period to DM, analysing nationwide data on screen-detected and interval cancers. Data of 7.3 million screens in women aged 49-74, between 2004 and 2011, were linked to the Netherlands Cancer Registry to obtain data on interval cancers. Age-adjusted DRs, ICRs and recall rates (RR) per 1000 screens and programme sensitivity and specificity were calculated by year, age and screening modality. RESULTS: 41,662 screen-detected and 16,160 interval cancers were analysed. The DR significantly increased from 5.13 (95% confidence interval (CI):5.00-5.30) in 2004 to 6.34 (95% CI:6.15-6.47) in 2011, for both in situ (2004:0.73;2011:1.24) and invasive cancers (2004:4.42;2011:5.07), whereas the ICR remained stable (2004: 2.16 (95% CI2.06-2.25);2011: 2.13 (95% CI:2.04-2.22)). The RR changed significantly from 14.0 to 21.4. Programme sensitivity significantly increased, mainly between ages 49-59, from 70.0% (95% CI:68.9-71.2) to 74.4% (95% CI:73.5-75.4) whereas specificity slightly declined (2004:99.1% (95% CI:99.09-99.13);2011:98.5% (95% CI:98.45-98.50)). The overall DR was significantly higher for DM than for SFM (6.24;5.36) as was programme sensitivity (73.6%;70.1%), the ICR was similar (2.19;2.20) and specificity was significantly lower for DM (98.5%;98.9%). CONCLUSIONS: During the transition from SFM to DM, there was a significant rise in DR and a stable ICR, leading to increased programme sensitivity. Although the recall rate increased, programme specificity remained high compared to other countries. These findings indicate that the performance of DM in a nationwide screening programme is not inferior to, and may be even better, than that of SFM.

Is the incidence of advanced-stage breast cancer affected by whether women attend a steady-state screening program?

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

The effect of population-based mammography screening in Dutch municipalities on breast cancer mortality: 20 years of follow-up.

Long-term follow-up data on the effects of screening are scarce, and debate exists on the relative contribution of screening versus treatment to breast cancer mortality reduction. Our aim was therefore to assess the long-term effect of screening by age and time of implementation. We obtained data on 69,630 breast cancer deaths between 1980 and 2010 by municipality (N = 431) and age of death (40-79) in the Netherlands. Breast cancer mortality trends were analyzed by defining the municipality-specific calendar year of introduction of screening as Year 0. Additionally, log-linear Poisson regression was used to estimate the turning point in the trend after Year 0, per municipality, and the annual percentage change (APC) before and after this point. Twenty years after introduction of screening breast cancer mortality was reduced by 30% in women aged 55-74 and by 34% in women aged 75-79, compared to Year 0. A similar and significant decrease was present in municipalities that started early (1987-1992) and late (1995-1997) with screening, despite the difference in availability of effective adjuvant treatment. In the age groups 55-74 and 75-79, the turning point in the trend in breast cancer mortality was estimated in Years 2 and 6 after the introduction of screening, respectively, after which mortality decreased significantly by 1.9% and 2.6% annually. These findings show that the implementation of mammography screening in Dutch municipalities is associated with a significant decline in breast cancer mortality in women aged 55-79, irrespective of time of implementation.

Cost-effectiveness of digital mammography screening before the age of 50 in The Netherlands.

In the Netherlands, routine mammography screening starts at age 50. This starting age may have to be reconsidered because of the increasing breast cancer incidence among women aged 40 to 49 and the recent implementation of digital mammography. We assessed the cost-effectiveness of digital mammography screening that starts between age 40 and 49, using a microsimulation model. Women were screened before age 50, in addition to the current programme (biennial 50-74). Screening strategies varied in starting age (between 40 and 50) and frequency (annual or biennial). The numbers of breast cancers diagnosed, life-years gained (LYG) and breast cancer deaths averted were predicted and incremental cost-effectiveness ratios (ICERs) were calculated to compare screening scenarios. Biennial screening from age 50 to 74 (current strategy) was estimated to gain 157 life years per 1,000 women with lifelong follow-up, compared to a situation without screening, and cost €3,376/LYG (3.5% discounted). Additional screening increased the number of LYG, compared to no screening, ranging from 168 to 242. The costs to generate one additional LYG (i.e., ICER), comparing a screening strategy to the less intensive alternative, were estimated at €5,329 (biennial 48-74 vs. current strategy), €7,628 (biennial 45-74 vs. biennial 48-74), €10,826 (biennial 40-74 vs. biennial 45-74) and €18,759 (annual 40-49 + biennial 50-74 vs. biennial 40-74). Other strategies (49 + biennial 50-74 and annual 45-49 + biennial 50-74) resulted in less favourable ICERs. These findings show that extending the Dutch screening programme by screening between age 40 and 49 is cost-effective, particularly for biennial strategies.

The effects of population-based mammography screening starting between age 40 and 50 in the presence of adjuvant systemic therapy.

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

International variation in management of screen-detected ductal carcinoma in situ of the breast.

BACKGROUND: Ductal carcinoma in situ (DCIS) incidence has grown with the implementation of screening and its detection varies across International Cancer Screening Network (ICSN) countries. The aim of this survey is to describe the management of screen-detected DCIS in ICSN countries and to evaluate the potential for treatment related morbidity. METHODS: We sought screen-detected DCIS data from the ICSN countries identified during 2004-2008. We adopted standardised data collection forms and analysis and explored DCIS diagnosis and treatment processes ranging from pre-operative diagnosis to type of surgery and radiotherapy. RESULTS: Twelve countries contributed data from a total of 15 screening programmes, all from Europe except the United States of America and Japan. Among women aged 50-69 years, 7,176,050 screening tests and 5324 screen-detected DCIS were reported. From 21% to 93% of DCIS had a pre-operative diagnosis (PO); 67-90% of DCIS received breast conservation surgery (BCS), and in 41-100% of the cases this was followed by radiotherapy; 6.4-59% received sentinel lymph node biopsy (SLNB) only and 0.8-49% axillary dissection (ALND) with 0.6% (range by programmes 0-8.1%) being node positive. Among BCS patients 35% received SLNB only and 4.8% received ALND. Starting in 2006, PO and SLNB use increased while ALND remained stable. SLNB and ALND were associated with larger size and higher grade DCIS lesions. CONCLUSIONS: Variation in DCIS management among screened women is wide and includes lymph node surgery beyond what is currently recommended. This indicates the presence of varying levels of overtreatment and the potential for its reduction.

Nation-wide data on screening performance during the transition to digital mammography: observations in 6 million screens.

PURPOSE: To critically evaluate and confirm previous results regarding the diagnostic accuracy of digital mammography screening (DM), compared to screen-film mammography (SFM) in the whole Dutch screening programme, in the period of 2004-2010, during which a full transition from SFM to DM was made. MATERIALS AND METHODS: 1.5 million DM and 4.6 million SFM were read in the Dutch national breast cancer screening programme in the period of 2004-2010. We evaluated recall rate, detection rate, positive predictive value and tumour-size distribution for younger and older women, for first time participants and women having a timely subsequent screen. We compared DM screens read by radiologists reading DM and SFM (DM-group) to SFM screens read by these radiologists (SFM-group) and to SFM screens read by radiologists reading only SFM (SFMonly-group). RESULTS: Recall rate was 2.0% (95% confidence interval (C.I.): 2.0; 2.1) in the DM-group, compared to 1.6% (95% C.I.: 1.6; 1.6) in the SFM-group and 1.6% (95% C.I.: 1.5; 1.6) in the SFM only-group. The overall detection rates were 5.9/1000 screens (95% C.I.: 5.7; 6.0) in the DM-group, 5.1/1000 screens (95% C.I.: 5.0; 5.2) in the SFM-group and 5.0/1000 screens (95% C.I.: 5.0; 5.1) in the SFM only-group. Detection rate rose most markedly in younger women (age 49-54) from 4.0/1000 screens to 5.1/1000 screens (p-value<0.001). Positive predictive value (PPV) in DM rose from 18.4% (95% C.I.: 14.6; 23.1) in 2004 to 32.5% (95% C.I.: 31.7; 33.2) in 2010. Detection rate rose in SFM-group from 5.0/1000 screens (95% C.I.: 4.7; 5.3) in 2004 to 5.5/1000 screens (95% C.I.: 5.2; 5.7) in 2010. Detection rate in DM-group rose mostly due to ductal carcinoma in situ (DCIS) detection especially in younger women/first screens. The proportion of T1a tumours was significantly higher in DM-group; otherwise size distribution did not change significantly for invasive carcinoma. Recall rates were variable between different screening regions. CONCLUSION: In accordance to previous, smaller, studies, we can confirm that DM has a higher detection rate compared to SFM, at the cost of a higher recall rate and lower PPV. More DCIS and a higher fraction of very small tumours were detected with DM, which has positive consequences for the stage shift as a result of mass screening.

Do women make an informed choice about participating in breast cancer screening? A survey among women invited for a first mammography screening examination.

OBJECTIVE: To determine the level of informed choice in women invited for breast cancer screening for the first time. METHODS: To determine the content of decision-relevant knowledge, 16 experts were asked to judge whether each of 51 topics represented essential information to enable informed choices. To assess the level of informed choices, a questionnaire was then sent to all 460 invited women in the south-western part of the Netherlands who turned 50 in August 2008. RESULTS: Of all 229 respondents, 95% were deemed to have sufficient knowledge as they answered at least 8 out of 13 items correctly. In 90% there was consistency between intention (not) to participate and attitude. As a result, 88% made an informed choice. Sixty-eight percent of women responded correctly on the item of over-diagnosis. Even if all non-respondents were assumed to have no knowledge, 50% of the total group invited to participate still had sufficient knowledge. CONCLUSIONS: Women were deemed to have sufficient relevant knowledge of the benefits and harms if they answered at least half of the items correctly. PRACTICE IMPLICATIONS: To further increase informed choices in breast cancer screening, information on some of the possible harms merits further attention.

Mammography screening and risk of breast cancer death: a population-based case-control study.

BACKGROUND: Because the efficacy of mammography screening had been shown in randomized controlled trials, the focus has turned on its effectiveness within the daily practice. Using individual data of women invited to screening, we conducted a case-control study to assess the effectiveness of the Dutch population-based program of mammography screening. METHODS: Cases were women who died from breast cancer between 1995 and 2003 and were closely matched to five controls on year of birth, year of first invitation, and number of invitations before case's diagnosis. ORs and 95% confidence intervals (CI) for the association between attending either of three screening examinations prior to diagnosis and the risk of breast cancer death were calculated using conditional logistic regression and corrected for self-selection bias. RESULTS: We included 755 cases and 3,739 matched controls. Among the cases, 29.8% was screen-detected, 34.3% interval-detected, and 35.9% never-screened. About 29.5% of the never-screened cases had stage IV tumor compared with 5.3% of the screen-detected and 15.1% of the interval-detected cases. The OR (95% CIs), all ages (49-75 years), was 0.51 (0.40-0.66) and for the age groups 50-69, 50-75, and 70-75 years were 0.61 (0.47-0.79), 0.52 (CI 0.41-0.67), and 0.16 (0.09-0.29), respectively. CONCLUSION: The study provides evidence for a beneficial effect of early detection by mammography screening in reducing the risk of breast cancer death among women invited to and who attended the screening. IMPACT: This is the first case-control study that accurately accounts for equal screening opportunity for both cases and matched controls by number of invitations before case's diagnosis.

Two-view versus single-view mammography at subsequent screening in a region of the Dutch breast screening programme.

We retrospectively determined the effect of analogue two-view mammography versus single-view mammography at subsequent screens on breast cancer detection and determined financial consequences for a current digital mammography setting. Two screening radiologists reviewed the mammograms of 536 screen detected cancers (SDCs) and 171 interval cancers (ICs) with single-view mammography (medio-lateral-oblique view) at the last but one screen (SDCs) or latest screen (ICs). They determined whether two-view mammography at the last (but one) screen could have increased the cancer detection rate at that screening round. For subsequent screens, the radiologists also assessed the percentage of SDCs and ICs that had been missed at previous two-view screening mammography (SDC) or latest two-view screening (IC), respectively. Additional personnel and digital storage costs for standard two-view mammography at subsequent screening were calculated for digital screening. Two-view mammography could have facilitated earlier cancer detection in 40.9% (219/536) of SDCs and 39.8% (68/171) of ICs. For two-view screens, 24.4% of SDCs (213/871) were missed at previous two-view screening and 29.3% of ICs (110/375) were missed at the latest screen. Overall costs increase € 1.03/screen after implementation of digital two-view mammography. Standard two-view mammography at subsequent screening may modestly increase cancer detection at an earlier stage, whereas additional screening costs are limited.

Digital mammography screening: weighing reduced mortality against increased overdiagnosis.

OBJECTIVE: Digital mammography has been shown to increase the detection of ductal carcinoma in situ (DCIS) compared to screen-film mammography. The benefits and risks of such an increase were assessed. METHODS: Breast cancer detection rates were compared between 502,574 screen-film and 83,976 digital mammograms performed between 2004 and 2006 among Dutch screening participants. The detection rates were then modeled using a baseline model and two extreme models that respectively assumed a high rate of progression and no progression of preclinical DCIS to invasive cancer. With these models, breast cancer mortality and overdiagnosis were predicted. RESULTS: The DCIS detection rate was significantly higher at digital mammography (1.2 per 1000 mammograms (95% C.I. 1.0-1.5)) than at screen-film mammography (0.7 per 1000 mammograms (95% C.I. 0.6-0.7)). Consequently, 287 (range progressive- non progressive model: 1-598) extra breast cancer deaths per 1,000,000 women (a 4.4% increase) were predicted to be prevented. An extra 401 (range: 165-2271) cancers would be overdiagnosed (a 21% increase). CONCLUSION: Modeling predicted that digital mammography screening would further reduce breast cancer mortality by 4.4%, at a 21% increased overdiagnosis rate. The consequences of digital screening, however, are sensitive to underlying assumptions on the natural history of DCIS.

Interpreting overdiagnosis estimates in population-based mammography screening.

Estimates of overdiagnosis in mammography screening range from 1% to 54%. This review explains such variations using gradual implementation of mammography screening in the Netherlands as an example. Breast cancer incidence without screening was predicted with a micro-simulation model. Observed breast cancer incidence (including ductal carcinoma in situ and invasive breast cancer) was modeled and compared with predicted incidence without screening during various phases of screening program implementation. Overdiagnosis was calculated as the difference between the modeled number of breast cancers with and the predicted number of breast cancers without screening. Estimating overdiagnosis annually between 1990 and 2006 illustrated the importance of the time at which overdiagnosis is measured. Overdiagnosis was also calculated using several estimators identified from the literature. The estimated overdiagnosis rate peaked during the implementation phase of screening, at 11.4% of all predicted cancers in women aged 0-100 years in the absence of screening. At steady-state screening, in 2006, this estimate had decreased to 2.8%. When different estimators were used, the overdiagnosis rate in 2006 ranged from 3.6% (screening age or older) to 9.7% (screening age only). The authors concluded that the estimated overdiagnosis rate in 2006 could vary by a factor of 3.5 when different denominators were used. Calculations based on earlier screening program phases may overestimate overdiagnosis by a factor 4. Sufficient follow-up and agreement regarding the chosen estimator are needed to obtain reliable estimates.

Life expectancy of screen-detected invasive breast cancer patients compared with women invited to the Nijmegen screening program.

BACKGROUND: Screening can lead to earlier detection of breast cancer and thus to an improvement in survival. The authors studied the life expectancy of women with screen-detected invasive breast cancer (patients) compared with women invited to the breast cancer screening program in Nijmegen, the Netherlands (comparison group). METHODS: Each patient diagnosed between 1975 and 2006 was randomly age-matched with a woman invited in the same calendar year and free from breast cancer at the time of diagnosis of the patient. Survival analyses were performed to study differences in life expectancy. RESULTS: The life expectancy for 858 patients was 6 years shorter than for the comparison group. However, for 360 patients with small (<15 mm) invasive breast cancer, life expectancy was similar to that of the comparison group. In contrast, for patients detected with larger tumors (> or = 15 mm) the life expectancy was 6 to 12 years shorter, depending on tumor size. Furthermore, life expectancy was modified by screening history. For patients who had a negative screening examination 2 years before the detection of their breast cancer, the difference in life expectancy from the comparison group became smaller for the larger tumor sizes (> or = 15 mm). CONCLUSIONS: In conclusion, about 40% (360 of 858) of all women with invasive screen-detected breast cancer have the same life expectancy as women from the comparison group (reflecting the general population). For women diagnosed with larger tumors at diagnosis, life expectancy diminishes with increasing tumor size and is modified by screening history.

Comparing interval breast cancer rates in Norway and North Carolina: results and challenges.

OBJECTIVE: To compare interval breast cancer rates (ICR) between a biennial organized screening programme in Norway and annual opportunistic screening in North Carolina (NC) for different conceptualizations of interval cancer. SETTING: Two regions with different screening practices and performance. METHODS: 620,145 subsequent screens (1996-2002) performed in women aged 50-69 and 1280 interval cancers were analysed. Various definitions and quantification methods for interval cancers were compared. RESULTS: ICR for one year follow-up were lower in Norway compared with NC both when the rate was based on all screens (0.54 versus 1.29 per 1000 screens), negative final assessments (0.54 versus 1.29 per 1000 screens), and negative screening assessments (0.53 versus 1.28 per 1000 screens). The rate of ductal carcinoma in situ was significantly lower in Norway than in NC for cases diagnosed in both the first and second year after screening. The distributions of histopathological tumour size and lymph node involvement in invasive cases did not differ between the two regions for interval cancers diagnosed during the first year after screening. In contrast, in the second year after screening, tumour characteristics remained stable in Norway but became prognostically more favorable in NC. CONCLUSION: Even when applying a common set of definitions of interval cancer, the ICR was lower in Norway than in NC. Different definitions of interval cancer did not influence the ICR within Norway or NC. Organization of screening and screening performance might be major contributors to the differences in ICR between Norway and NC.

Cost-effectiveness of opportunistic versus organised mammography screening in Switzerland.

BACKGROUND: Various centralised mammography screening programmes have shown to reduce breast cancer mortality at reasonable costs. However, mammography screening is not necessarily cost-effective in every situation. Opportunistic screening, the predominant screening modality in several European countries, may under certain circumstances be a cost-effective alternative. In this study, we compared the cost-effectiveness of both screening modalities in Switzerland. METHODS: Using micro-simulation modelling, we predicted the effects and costs of biennial mammography screening for 50-69 years old women between 1999 and 2020, in the Swiss female population aged 30-70 in 1999. A sensitivity analysis on the test sensitivity of opportunistic screening was performed. RESULTS: Organised mammography screening with an 80% participation rate yielded a breast cancer mortality reduction of 13%. Twenty years after the start of screening, the predicted annual breast cancer mortality was 25% lower than in a situation without screening. The 3% discounted cost-effectiveness ratio of organised mammography screening was euro11,512 per life year gained. Opportunistic screening with a similar participation rate was comparably effective, but at twice the costs: euro22,671-24,707 per life year gained. This was mainly related to the high costs of opportunistic mammography and frequent use of imaging diagnostics in combination with an opportunistic mammogram. CONCLUSION: Although data on the performance of opportunistic screening are limited, both opportunistic and organised mammography screening seem effective in reducing breast cancer mortality in Switzerland. However, for opportunistic screening to become equally cost-effective as organised screening, costs and use of additional diagnostics should be reduced.

Impressive time-related influence of the Dutch screening programme on breast cancer incidence and mortality, 1975-2006.

The aim of this study was to assess changes in the trends in breast cancer mortality and incidence from 1975 to 2006 among Dutch women, in relation to the implementation of the national breast cancer screening programme. Screening started in 1989 for women aged 50-69 and was extended to women aged 70-75 years in 1998 (attendance rate approximately >80%). A joinpoint Poisson regression analysis was used to identify significant changes in rates over time. Breast cancer mortality rates increased until 1994 (age group 35-84), but thereafter showed a marked decline of 2.3-2.8% per annum for the age groups 55-64 and 65-74 years, respectively. For the age group of 75-84 years, a decrease started in the year 2001. In women aged 45-54, an early decline in breast cancer mortality rates was noted (1971-1980), which is ongoing from 1992. For all ages, breast cancer incidence rates showed an increase between 1989 and 1993, mainly caused by the age group 50-69, and thereafter, a moderate increase caused by age group 70-74 years. This increase can partly be explained by the introduction of screening. The results indicate an impressive decrease in breast cancer mortality in the age group invited for breast cancer screening, starting to show quite soon after implementation.

Utilization and cost of diagnostic imaging and biopsies following positive screening mammography in the southern breast cancer screening region of the Netherlands, 2000-2005.

We prospectively assessed trends in utilization and costs of diagnostic services of screen-positive women in a biennial breast cancer screening program for women aged 50-75 years. All 2,062 women with suspicious findings at screening mammography in the southern region of the Netherlands between 1 January 2000 and 1 July 2005 (158,997 screens) were included. Data were collected on any diagnostic examinations, interventional procedures, and surgical consultations with two-year follow-up. We used national reimbursement rates to estimate imaging costs and percutaneous biopsy costs. Cost prices, charged by hospitals, were used to estimate open surgical biopsy costs and surgical consultation costs. The largest increase in utilization of diagnostic procedures per 100 referrals was observed for axillary ultrasound (from 3.9 in 2000 to 33.5 in 2005) and for stereotactic core biopsy (from 2.1 in 2000 to 26.8 in 2005). Per 100 referrals, the open surgical biopsy rate decreased from 34.7 (2000) to 4.6 (2005) and the number of outpatient surgical consultations fluctuated between 269.8 (2000) and 309.7 (2004). Mean costs for the diagnosis of one cancer were Euro1,501 and ranged from Euro1,223 (2002) to Euro1,647 (2003). Surgical biopsies comprised 54.1% of total diagnostic costs for women screened in 2000, but decreased to 9.9% for women screened in 2005. Imaging costs increased from 23.7 to 43.8%, percutaneous biopsy costs from 9.9 to 27.2%, and consultation costs from 12.3 to 19.1%. We conclude that diagnostic costs per screen-detected cancer remained fairly stable through the years, although huge changes in the use of different diagnostic procedures were observed.

Introduction of additional double reading of mammograms by radiographers: effects on a biennial screening programme outcome.

PURPOSE: To determine the effect of introducing radiographer double reading, in addition to standard radiologist double reading, on screening mammography outcome. METHODS: In period A, 66,225 mammograms were read by two screening radiologists. In period B, 78,325 mammograms were read by two radiographers in addition and radiologists were blinded to the referral opinion of the radiographers. Mammograms, for which only radiographers had suggested referral, (i.e. cases that would only be referred by technologists) were re-evaluated by the screening radiologists. Women were referred if at least one radiologist considered this necessary, and diagnostic costs of these additional referrals were estimated. RESULTS: In period A, 322 cancers were diagnosed after referral of 678 women. During period B, radiologists initially referred 1122 patients and 411 cancers were detected. Radiologists' referral rate was higher in period B than in period A (1.43% versus 1.02%, p<0.001), as well as the cancer detection rate per 1000 women screened (CDR) (5.25 versus 4.86, p=0.3). The positive predictive value of referral (PPV) was 36.6% versus 47.5% (p<0.001). In period B, radiologist review of 544 additional positive radiographer readings led to 102 extra referrals, with 29 additional cancers detected, resulting in an overall referral rate of 1.56% (compared to period A, p<0.001), an overall CDR of 5.62 (p=0.048) and an overall PPV of 35.9% (p<0.001). Workup expenses of the 102 additional referrals were euro60,274. CONCLUSION: Additional radiographer double reading detected cancers that would have been missed by radiologists. Mean expenses for diagnostic confirmation of these extra cancers was euro2078 per cancer.