Bedrich Vitak

Mammography service screening and mortality in breast cancer patients: 20-year follow-up before and after introduction of screening

BACKGROUND The long term effect of mammographic service screening is not well established. We aimed to assess the long-term effect of mammographic screening on death from breast cancer, taking into account potential biases from self-selection, changes in breast cancer incidence, and classification of cause of death. METHODS We compared deaths from breast cancer diagnosed in the 20 years before screening was introduced (1958-77) with those from breast cancer diagnosed in the 20 years after the introduction of screening (1978-97) in two Swedish counties, in 210000 women aged 20-69 years. We also compared deaths from all cancers and from all causes in patients diagnosed with breast cancer in the 20 years before and after screening was introduced. In the analysis, data were stratified into age-groups invited for screening (40-69 years) and not invited (20-39 years), and by whether or not the women had actually received screening. We also analysed mortality for the 40-49-year age-group separately. FINDINGS The unadjusted risk of death from breast cancer dropped significantly in the second screening period compared with the first in women aged 40-69 years (relative risk [RR] 0.77 [95% CI 0.7-0.85]; p<0.0001). No such decline was seen in 20-39 year olds. After adjustment for age, self-selection bias, and changes in breast-cancer incidence in the 40-69 years age-group, breast-cancer mortality was reduced in women who were screened (0.56; 0.49-0.64 p<0.0001), in those who were not screened (0.84 [0.71-0.99]; p=0.03), and in screened and unscreened women combined (0.59 [0.53-0.66]; p<0.0001). After adjustment for age, self-selection bias, and changes in incidence in the 40-49-year age-group, deaths from breast cancer fell significantly in those who were screened (0.52 [0.4-0.67]; p<0.0001); and in all women, screened and unscreened combined (0.55 [0.44-0.7] p<0.0001) but not in unscreened women (p=0.2). In both 40-69-year and 40-49-year age-groups, reductions in deaths from all cancers and from all-causes in women with breast cancer were consistent with these results. INTERPRETATION Taking account of potential biases, changes in clinical practice and changes in the incidence of breast cancer, mammography screening is contributing to substantial reductions in breast cancer mortality in these two Swedish counties.

Beyond Randomized Controlled Trials Organized Mammographic Screening Substantially Reduces Breast Carcinoma Mortality

The efficacy of mammographic screening in the reduction of breast carcinoma mortality has been demonstrated in randomized controlled trials. However, the evaluation of organized screening outside of research settings (so‐called “service screening“) faces unique methodologic and conceptual challenges. The current study describes the evaluation of organized mammography screening in a clinical setting and demonstrates the benefit obtained from service screening in two Swedish counties.

THE SWEDISH TWO-COUNTY TRIAL TWENTY YEARS LATER: Updated Mortality Results and New Insights from Long-Term Follow-up

The benefit of invitation to mammographic screening observed in this trial is maintained as a highly significant 32% reduction in breast cancer mortality. Mammographic screening for breast cancer continues to save lives after up to 20 years. Screening derives this benefit by improving the distribution of tumors diagnosed with respect to prognostic categories based on node status, size, and histology of tumors. There is potential for modern screening programs with shorter interscreening intervals to achieve even greater improvements in prognostic category and greater reductions in breast cancer mortality. Mammography can discriminate a subpopulation of high-risk cases, those displaying casting-type calcifications on the mammogram, among very small tumors, with fundamental implications for diagnosis and treatment.

Swedish Two-County Trial: Impact of Mammographic Screening on Breast Cancer Mortality during 3 Decades

PURPOSE To estimate the long-term (29-year) effect of mammographic screening on breast cancer mortality in terms of both relative and absolute effects. MATERIALS AND METHODS This study was carried out under the auspices of the Swedish National Board of Health and Welfare. The board determined that, because randomization was at a community level and was to invitation to screening, informed verbal consent could be given by the participants when they attended the screening examination. A total of 133 065 women aged 40-74 years residing in two Swedish counties were randomized into a group invited to mammographic screening and a control group receiving usual care. Case status and cause of death were determined by the local trial end point committees and, independently, by an external committee. Mortality analysis was performed by using negative binomial regression. RESULTS There was a highly significant reduction in breast cancer mortality in women invited to screening according to both local end point committee data (relative risk [RR] = 0.69; 95% confidence interval: 0.56, 0.84; P < .0001) and consensus data (RR = 0.73; 95% confidence interval: 0.59, 0.89; P = .002). At 29 years of follow-up, the number of women needed to undergo screening for 7 years to prevent one breast cancer death was 414 according to local data and 519 according to consensus data. Most prevented breast cancer deaths would have occurred (in the absence of screening) after the first 10 years of follow-up. CONCLUSION Invitation to mammographic screening results in a highly significant decrease in breast cancer-specific mortality. Evaluation of the full impact of screening, in particular estimates of absolute benefit and number needed to screen, requires follow-up times exceeding 20 years because the observed number of breast cancer deaths prevented increases with increasing time of follow-up.

Absolute numbers of lives saved and overdiagnosis in breast cancer screening, from a randomized trial and from the Breast Screening Programme in England

Objectives To estimate the absolute numbers of breast cancer deaths prevented and the absolute numbers of tumours overdiagnosed in mammographic screening for breast cancer at ages 50–69 years. Setting The Swedish Two-County randomized trial of mammographic screening for breast cancer, and the UK Breast Screening Programme in England, ages 50–69 years. Methods We estimated the absolute numbers of deaths avoided and additional cases diagnosed in the study group (active study population) of the Swedish Two-County Trial, by comparison with the control group (passive study population). We estimated the same quantities for the mortality and incidence rates in England (1974–2004 and 1974–2003, respectively). We used Poisson regression for statistical inference. Results A substantial and significant reduction in breast cancer mortality was associated with screening in both the Two-County Trial (P < 0.001) and the screening programme in England (P < 0.001). The absolute benefits were estimated as 8.8 and 5.7 breast cancer deaths prevented per 1000 women screened for 20 years starting at age 50 from the Two-County Trial and screening programme in England, respectively. The corresponding estimated numbers of cases overdiagnosed per 1000 women screened for 20 years were, respectively, 4.3 and 2.3 per 1000. Conclusions The benefit of mammographic screening in terms of lives saved is greater in absolute terms than the harm in terms of overdiagnosis. Between 2 and 2.5 lives are saved for every overdiagnosed case.

Effectiveness of Population-Based Service Screening With Mammography for Women Ages 40 to 49 Years Evaluation of the Swedish Mammography Screening in Young Women (SCRY) Cohort

The effectiveness of mammography screening for women ages 40 to 49 years still is questioned, and few studies of the effectiveness of service screening for this age group have been conducted.

Correcting for non-compliance bias in case-control studies to evaluate cancer screening programmes

In the evaluation of uncontrolled service screening programmes for cancer, the case-control design is sometimes used, in which people who die from the disease in question are compared with live con ...

The relative contributions of screen-detected in situ and invasive breast carcinomas in reducing mortality from the disease

We aimed to quantify the benefits of detecting ductal carcinoma in situ (DCIS) and of downwards stage-shifting within invasive tumours in mammographic screening. Using data from the Swedish Two-County Trial of breast cancer screening, we examined the 20-year death rates from invasive tumours of stage II or worse, invasive tumours of stage I and DCIS. We then used these rates and their respective incidences in invited (active study population, ASP) and control (passive study population, PSP) arms of the trial, to estimate the numbers of deaths avoided by downward stage-shifting the larger stage II or worse tumours to stage I and the stage I cancers to DCIS. We also studied the association between the mortality reduction achieved and the proportion of DCIS cases detected in the randomised trials of breast cancer screening. In the Swedish Two County Trial, 141 breast cancer deaths were avoided in the ASP compared with the PSP at approximately 20 years of follow-up. Of these, 65% (91/141) were avoided as a result of stage-shifting from invasive stage II or worse to invasive stage I, and 5% (7/141) as a result of stage-shifting from invasive stage I to DCIS. If we assumed that 10% of stage II or worse tumours avoided were shifted not to stage I, but to DCIS, the estimated number of deaths prevented by shifting from invasive disease to in situ was 17, which is 12% of all deaths prevented. When the results of all the randomised trials of breast cancer screening were reviewed, there was no clear association between the percentage of DCIS cases diagnosed and the observed mortality reduction. We conclude that compared with downward stage-shifting of invasive tumours, detection of DCIS plays a small part in saving lives from breast cancer. Treatment decisions in DCIS, as in invasive carcinoma, should take full account of histopathological, clinical and radiological attributes of the tumour.

Number needed to screen: lives saved over 20 years of follow-up in mammographic screening

Objective: To estimate the number needed to screen with mammography to save one life, based on a stated amount of screening activity and long-term follow-up for breast cancer death. Setting: A randomised controlled trial of mammographic screening for breast cancer, with 77,080 women invited to screening and 55,985 not invited. The invited group was offered screening for seven years. Follow-up continued for a total of just over 20 years. Methods: Number needed to screen for seven years to save one life over 20 years was calculated by dividing the number screened (not the number invited) by the total number of lives saved. Similarly, we calculated the number of mammographic examinations required to save one life. Results: We estimate that the number of women needed to screen for seven years to save one life over 20 years is 465 (95% CI 324–819). The number of mammographic examinations needed to save one life was 1499 (95% CI 1046–2642). Conclusions: The number needed to screen to save one life is smaller than has been reported in the past. Mammographic screening is effective in absolute terms as well as relative. Long-term follow-up allowed us to estimate the absolute benefit with greater accuracy.

Interval cancers in the Norwegian breast cancer screening program: Frequency, characteristics and use of HRT

Breast cancers diagnosed between screening examinations among women who attend a breast cancer screening program are defined as interval cancers. The Norwegian Breast Cancer Screening Program started as a pilot project in 1996, and data from the first 2‐year interval are available. Our study quantifies interval cancers in the pilot project and explores characteristics and factors that may be associated with interval cancer. Interval cancers in the screening population were identified through the Cancer Registry of Norway. The frequency of invasive interval cancer was calculated as cases per 10,000 screened and as observed/expected ratio. Characteristics of the interval cancers were compared to screening‐detected and clinical cancers. Breast density was assessed in a blinded review of 3 categories of screening mammograms. Information on hormone replacement therapy (HRT) use was collected from a questionnaire. The frequency of invasive interval cancers was 18.2 (15.9–20.7) per 10,000 screened and the observed/expected ratio was 0.49 (0.43–0.56). The frequency in the second year of the interval was higher than reported from other programs. The median tumor size of the interval cancers was 19.5 mm and 44.0% of the patients had affected axillary lymph nodes. The interval cancer cases had higher proportions of dense breasts and reported use of HRT compared to screen normal and screening‐detected cases. The reported frequency of interval cancers is similar to comparable programs. The interval cancers differed significantly from the cancers detected in the first screening round and were more similar to clinical cancers. Interval cancer was associated with dense breasts and use of HRT. Screening programs must keep these associations in focus.