Ellen Paap

The impact of mammographic screening on breast cancer mortality in Europe: a review of observational studies

Objectives To assess the impact of population-based mammographic screening on breast cancer mortality in Europe, considering different methodologies and limitations of the data. Methods We conducted a systematic literature review of European trend studies (n = 17), incidence-based mortality (IBM) studies (n = 20) and case-control (CC) studies (n = 8). Estimates of the reduction in breast cancer mortality for women invited versus not invited and/or for women screened versus not screened were obtained. The results of IBM studies and CC studies were each pooled using a random effects meta-analysis. Results Twelve of the 17 trend studies quantified the impact of population-based screening on breast cancer mortality. The estimated breast cancer mortality reductions ranged from 1% to 9% per year in studies reporting an annual percentage change, and from 28% to 36% in those comparing post- and prescreening periods. In the IBM studies, the pooled mortality reduction was 25% (relative risk [RR] 0.75, 95% confidence interval [CI] 0.69–0.81) among invited women and 38% (RR 0.62, 95% CI 0.56–0.69) among those actually screened. The corresponding pooled estimates from the CC studies were 31% (odds ratio [OR] 0.69, 95% CI 0.57–0.83), and 48% (OR 0.52, 95% CI 0.42–0.65) adjusted for self-selection. Conclusions Valid observational designs are those where sufficient longitudinal individual data are available, directly linking a womans screening history to her cause of death. From such studies, the best ‘European’ estimate of breast cancer mortality reduction is 25–31% for women invited for screening, and 38–48% for women actually screened. Much of the current controversy on breast cancer screening is due to the use of inappropriate methodological approaches that are unable to capture the true effect of mammographic screening.

Increasingly strong reduction in breast cancer mortality due to screening

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

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

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

Comparison of a flexible versus a rigid breast compression paddle: pain experience, projected breast area, radiation dose and technical image quality

AbstractPurposeTo compare pain, projected breast area, radiation dose and image quality between flexible (FP) and rigid (RP) breast compression paddles.MethodsThe study was conducted in a Dutch mammographic screening unit (288 women). To compare both paddles one additional image with RP was made, consisting of either a mediolateral-oblique (MLO) or craniocaudal-view (CC). Pain experience was scored using the Numeric Rating Scale (NRS). Projected breast area was estimated using computer software. Radiation dose was estimated using the model by Dance. Image quality was reviewed by three radiologists and three radiographers.ResultsThere was no difference in pain experience between both paddles (mean difference NRS: 0.08 ± 0.08, p = 0.32). Mean radiation dose was 4.5 % lower with FP (0.09 ± 0.01 p = 0.00). On MLO-images, the projected breast area was 0.79 % larger with FP. Paired evaluation of image quality indicated that FP removed fibroglandular tissue from the image area and reduced contrast in the clinically relevant retroglandular area at chest wall side.ConclusionsAlthough FP performed slightly better in the projected breast area, it moved breast tissue from the image area at chest wall side. RP showed better contrast, especially in the retroglandular area. We therefore recommend the use of RP for standard MLO and CC views.Key points• Pain experience showed no difference between flexible and rigid breast compression paddles. • Flexible paddles do not depict clinically relevant retroglandular areas as well. • Flexible paddles move breast tissue from image area at the chest wall side. • Rigid paddles depict more breast tissue and shows better contrast. • Rigid breast compression paddles are recommended for standard mediolateral-oblique and craniocaudal views.

Effective biennial mammographic screening in women aged 40-49.

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

Minor influence of self-selection bias on the effectiveness of breast cancer screening in case-control studies in the Netherlands.

Background Self-selection bias is considered to be a problem when evaluating the effectiveness of breast cancer service screening in case-control studies. Objective Using the incidence-based mortality method (IBM), a correction factor for the potential influence of self-selection can be derived from a group of non-screened women and a group of not-invited women. Methods Breast cancer patients, diagnosed in 1990–1995 and between the ages of 50 to 70, were selected from the Netherlands Cancer Registry and five screening regions in the Netherlands. Person-years were calculated for non-screened and not-invited women by using population data available on the number of women invited, the number of women screened and the total population. Incidence-based breast cancer mortality rates according to screening status were calculated for the five screening regions. Results Between 1990–1995, 15,541 patients were diagnosed with breast cancer. An analysis of ten-year follow-up after diagnosis resulted in 3903 breast cancer deaths, of which 2631 were not-invited and 345 were non-screened. Poisson regression analysis showed heterogeneity between the regions with a range of IBM ratios from 0.64 (95% CI: 0.46–0.90) to 1.08 (95% CI: 0.82–1.43). Conclusions Heterogeneity between the regions stresses the importance of a country- and/or region-specific estimate of self-selection. Adjusting for self-selection bias in the regional case-control studies would not change the breast cancer mortality reduction in three regions and would result in an even larger effect in two regions. Looking at the range of IBM ratios the overall influence of self-selection in the Netherlands is minor.

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

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

A rationale for starting breast cancer screening under age 50

Most countries which have implemented service screening on breast cancer invite women from age 50 [1]. With regard to younger women, findings from the UK age trial [2] showed the same trend as previous studies [3] that screening below age 50 has a positive effect on breast cancer mortality. For women screened at 40–49, Moss et al. [2] reported a breast cancer mortality reduction of 17% at 10-year follow up (relative risk 0.83, 95% confidence interval 0.66–1.04). The statistical nonsignificance of these results hampers decisions on lowering the starting age of mammographic screening. On the other hand, these results also cast doubts on the validity of age 50 as the lower age limit for breast screening. We evaluated (surrogate) impact indicators for mortality reduction, such as screen-detected lymph node status, tumour size, and tumour stage; sensitivity of the mammographical screening test; mammographic density; and breast cancer occurrence along the continuum of age, to address the question whether breast screening should be extended to women under age 50. Our analysis thus addresses the matter of a gradual change with age in screening outcome measures instead of a sudden change, which seems to appear if data are analysed according to age dichotomised in <50 and ‡50. Data were used from the Nijmegen breast-screening programme in The Netherlands [4]. Tumour stage II or worse represents breast cancer with either tumour size £2 cm and lymph node positivity or tumour size >2 cm; stage I represents breast cancer with tumour size £2 cm and a negative lymph node status; and ductal carcinoma in situ was classified as stage 0. We calculated the rate of invasive disease with lymph node positive breast cancer, the rate of invasive disease with a diameter >2 cm, and the rate of tumour stage II or worse. The mammographic screening test sensitivity was calculated as the number of breast cancer detected through screening divided by the number of breast cancer detected through screening plus the number of interval cancers. Mammographic density was classified by a radiologist in one of two categories depending on the relative amount of dense tissue: £25% was defined as lucent and ‡26% as dense [5]. Dutch breast cancer incidence rates were calculated for two calendar years (1989 and 2003) with data from the National Cancer Registry and Statistics Netherlands. We observed a gradual change with increasing age in screening outcome measures and breast cancer incidence (see Figures 1 and 2). This confirms the results from an earlier study by Kopans et al. [6] that screening outcome measures do not change abruptly at age 50. Between 40 and 60 years, the detection rate of lymph node-positive disease remained roughly the same 0.75 per 1000 screenees; the detection rate of tumour size >2 cm rose from 0.4 per 1000 women screened at age 45 to 0.5 per 1000 women screened at age 55; the detection rate of stage II or worse rose from 0.8 per 1000 screenees at age 45 to 0.9 per 1000 screenees at age 55; the mammographic screening test sensitivity rose from 42% at age 45 to 55% at age 55; the number of women with dense breasts gradually declined from 50% at age 46 to 10% at age 60 (Figure 1); and the breast cancer incidence rates rose in 1989 and 2003 (Figure 2). Breast cancer incidence rates in 2003 were higher compared with 1989, an increase which is not only limited to the age group eligible for screening but also between 45 and 50 years of age. The breast cancer incidence rate at the start of the national letters to the editor Annals of Oncology

Mammography in females with an implanted medical device: impact on image quality, pain and anxiety

OBJECTIVE To assess the image quality of mammograms in females with an implanted medical device (IMD), to evaluate pain and anxiety during mammography in these females and to investigate the experience of radiographers. METHODS Image quality was evaluated by two radiographers and one radiologist in the images of females with an IMD participating in the Dutch screening programme (clients). Pain and anxiety were scored using a Numeric Rating Scale in both clients visiting a screening organization and patients from the Isala Hospital, Zwolle. Experience of screening radiographers was collected with a questionnaire. RESULTS Images of the breast with IMD showed reduced contrast in craniocaudal (CC) and mediolateral-oblique (MLO) views [by both the radiographers and radiologist (range: 11-29%)], less projected breast tissue [only radiographers; CC lateral side: 25.5%, 95% confidence interval (CI): 18.7-32.2] and reduced projection of the pectoral muscle (only radiographers; MLO width pectoral muscle: 31.5%, 95% CI: 24.4-38.7). Clients experienced more pain and anxiety during mammography in the breast with IMD compared to the breast without IMD in the breast (pain difference CC: 0.48 ± 0.16, p = 0.003; pain difference MLO: 0.46 ± 0.16, p = 0.004; anxiety difference 1.30 ± 0.22; p < 0.001). Patients experienced more pain (1.05 ± 0.12; p < 0.001) and anxiety (1.22 ± 0.15; p < 0.001) after placement of IMD. Radiographers are more cautious, more anxious and use less compression during mammography of breasts with IMD. CONCLUSION Image quality in a breast with an IMD could be improved by projecting more breast tissue on the mammogram, thereby including (part of) the IMD between the paddles, if required. In addition, radiographers should pay sufficient attention to reducing discomfort both before and during the screening examination. ADVANCES IN KNOWLEDGE Little is known about the quality of mammography in females with an IMD or how these females and radiographers experience the screening examination. The results of our study showed that having an IMD could result in a suboptimal mammogram and increased discomfort.

Residual confounding after adjustment for age: a minor issue in breast cancer screening effectiveness

Residual confounding, after adjustment for age, is the major criticism of observational studies on breast cancer screening effectiveness. We developed realistic scenarios for the prevalence and strength of risk factors on screened and not screened groups, and explored the impact of residual confounding bias. Our results demonstrate that residual confounding bias is a minor issue in screening programme evaluations.