Incidence-based Breast Cancer Mortality Research Articles

Incidence-Based Breast Cancer Mortality Trends in Estonia Before and After the Introduction of Organized Mammography Screening: A Register-Based Study.

Despite the relatively low breast cancer incidence in Estonia, mortality remains high, and participation in mammography screening is below the recommended 70%. The objective of this register-based study was to evaluate incidence-based (IB) breast cancer mortality before and after the introduction of organized mammography screening in 2004. Breast cancer deaths individually linked to breast cancer diagnosis were obtained from the Estonian Cancer Registry and used for calculating IB mortality. We compared age-specific IB mortality rates across 5-year birth cohorts and 5-year periods. Poisson regression was used to compare IB mortality for one age group invited to screening (50-63) and three age groups not invited to screening (30-49, 65-69, and 70+) during two periods before and after screening initiation (1993-2003 and 2004-2014). Joinpoint regression was used for age-standardized incidence and IB mortality trends. Age-standardized IB mortality has been decreasing since 1997. Age-specific IB mortality for birth cohorts never exposed to screening showed a continuous increase with age, while in cohorts exposed to organized screening the mortality curve flattened or declined after the age of first invitation. Significant decreases in mortality from 1993-2003 to 2004-2014 were seen in the 30-49 (age-adjusted rate ratio 0.51, 95% CI 90.42-0.63) and 50-63 (0.65, 95% CI 0.56-0.74) age groups, while no decline was seen in the 65-69 and 70+ age groups. The age specific IB mortality curves in birth cohorts exposed to screening and the significant mortality decline in the target age group after the initiation of the organized program suggest a beneficial effect of screening. Improved treatment without screening has not reduced mortality in older age groups. Our results support raising the upper screening age limit to 74 years.

Reply to Yaffe, M.J. Correction for Self-Selection in Breast Cancer Screening. Comment on "Dibden et al. Worldwide Review and Meta-Analysis of Cohort Studies Measuring the Effect of Mammography Screening Programmes on Incidence-Based Breast Cancer Mortality. Cancers 2020, 12, 976".

In his Comment [...].

Correction for Self-Selection in Breast Cancer Screening. Comment on Dibden et al. Worldwide Review and Meta-Analysis of Cohort Studies Measuring the Effect of Mammography Screening Programmes on Incidence-Based Breast Cancer Mortality. Cancers 2020, 12, 976.

Observational studies of cancer screening are subject to bias associated with the self-selection of screening participants for whom the underlying probability of cancer death may be different from those who do not participate. Dibden et al. reviewed data on mortality reduction from 27 observational studies of mammography screening expressed in terms of relative risk for women who were screened versus not screened. Results were given, both unadjusted and after application of a correction for self-selection. The correction was based on a constant (1.17)-the ratio of risks of death in screening non-attenders versus those not invited, derived from a Swedish study. For some of the studies this correction had a large effect in diminishing the measured mortality benefit associated with screening. In particular, application to The Pan-Canadian Study of Mammography Screening, a study whose authors had previously tested for and found no evidence of self-selection bias, caused the estimated benefit to decrease from 40% to 10%. The appropriateness of applying a correction based on a constant to a population whose healthcare environment and screening participation rates are very different from those from which it was derived is questionable.

Beneficial Effect of Consecutive Screening Mammography Examinations on Mortality from Breast Cancer: A Prospective Study.

Background Previously, the risk of death from breast cancer was analyzed for women participating versus those not participating in the last screening examination before breast cancer diagnosis. Consecutive attendance patterns may further refine estimates. Purpose To estimate the effect of participation in successive mammographic screening examinations on breast cancer mortality. Materials and Methods Participation data for Swedish women eligible for screening mammography in nine counties from 1992 to 2016 were linked with data from registries and regional cancer centers for breast cancer diagnosis, cause, and date of death (Uppsala University ethics committee registration number: 2017/147). Incidence-based breast cancer mortality was calculated by whether the women had participated in the most recent screening examination prior to diagnosis only (intermittent participants), the penultimate screening examination only (lapsed participants), both examinations (serial participants), or neither examination (serial nonparticipants). Rates were analyzed with Poisson regression. We also analyzed incidence of breast cancers proving fatal within 10 years. Results Data were available for a total average population of 549 091 women (average age, 58.9 years ± 6.7 [standard deviation]). The numbers of participants in the four groups were as follows: serial participants, 392 135; intermittent participants, 41 746; lapsed participants, 30 945; and serial nonparticipants, 84 265. Serial participants had a 49% lower risk of breast cancer mortality (relative risk [RR], 0.51; 95% CI: 0.48, 0.55; P < .001) and a 50% lower risk of death from breast cancer within 10 years of diagnosis (RR, 0.50; 95% CI: 0.46, 0.55; P < .001) than serial nonparticipants. Lapsed and intermittent participants had a smaller reduction. Serial participants had significantly lower risk of both outcomes than lapsed or intermittent participants. Analyses correcting for potential biases made little difference to the results. Conclusion Women participating in the last two breast cancer screening examinations prior to breast cancer diagnosis had the largest reduction in breast cancer death. Missing either one of the last two examinations conferred a significantly higher risk. Published under a CC BY 4.0 license. Online supplemental material is available for this article. See also the editorial by Stephen A. Feig in this issue.

Effectiveness of Population-Based Service Screening with Mammography for Women Aged 70-74 Years in Sweden.

Consensus has been reached on the effectiveness of inviting women aged 50 to 69 years to mammography screening, but for older women, the evidence is scarce. The aim of this study was to estimate the marginal effectiveness of inviting women to mammography screening with an upper age limit of 74 years versus stopping at age 69 using data from the Swedish service-screening program. A cohort design was used to compare the breast cancer mortality in the period 1986 to 2012 between geographic areas and periods where women were invited to screening up to the age of 74 years (study group) with those where women were invited up to age 69 (control group). The study group and the control group were compared using the incidence-based breast cancer mortality rate ratio where only breast cancer deaths in cases diagnosed at 70 to 74 years of age were counted. After 20 years of follow-up, there were 1,040 and 1,173 breast cancer deaths in the study and the control group, respectively. The breast cancer mortality rate ratio for women invited up to age 74 versus women invited up to age 69 was 0.80 [95% confidence interval (CI): 0.75-0.85] after bias adjustments. The corresponding rate ratio for participating women was 0.73 (95% CI: 0.66-0.81). Continuing to screen women up to 74 years of age is effective compared with stopping screening at 69 years. This large long-term study will add to the knowledge of the effect of mammography screening for women 70 to 74 years.

Worldwide Review and Meta-Analysis of Cohort Studies Measuring the Effect of Mammography Screening Programmes on Incidence-Based Breast Cancer Mortality.

In 2012, the Euroscreen project published a review of incidence-based mortality evaluations of breast cancer screening programmes. In this paper, we update this review to October 2019 and expand its scope from Europe to worldwide. We carried out a systematic review of incidence-based mortality studies of breast cancer screening programmes, and a meta-analysis of the estimated effects of both invitation to screening and attendance at screening, with adjustment for self-selection bias, on incidence-based mortality from breast cancer. We found 27 valid studies. The results of the meta-analysis showed a significant 22% reduction in breast cancer mortality with invitation to screening, with a relative risk of 0.78 (95% CI 0.75–0.82), and a significant 33% reduction with actual attendance at screening (RR 0.67, 95% CI 0.61–0.75). Breast cancer screening in the routine healthcare setting continues to confer a substantial reduction in mortality from breast cancer.

Effect of organized mammography screening on breast cancer mortality: A population‐based cohort study in Norway

We aimed to estimate the effect of organized mammography screening on incidence-based breast cancer mortality by comparing changes in mortality among women eligible for screening to concurrent changes in younger and older ineligible women. In a county-wise balanced, open-cohort study, we used birth cohorts (1896-1982) to construct three age groups in both the historical and screening period: women eligible for screening, and younger or older women ineligible for screening. We included women diagnosed with breast cancer who died within the same age-period group during 1987-2010 (n = 4,903). We estimated relative incidence-based mortality rate ratios (relative MRR) comparing temporal changes in eligible women to concurrent changes in ineligible women. Additionally, we conducted analyses comparing the change in eligible women to younger, ineligible women with either continued accrual and follow-up period (eligible women only) or continued follow-up period. All three age groups experienced a reduction in mortality, but the decrease among eligible women was about the same among ineligible women (relative MRR = 1.05, 95% CI: (0.94-1.18)). Varying the definition of follow-up yielded similar results. Mammography screening was not associated with a larger breast cancer mortality reduction in women eligible relative to ineligible women.

Participation in Mammography Screening Accomplishes an Enduring and Significant Reduction in Breast Cancer Mortality in the Era of Modern Therapy: An Observational Study Spanning 52 Years

Background: A significant decrease in breast cancer mortality has been demonstrated in populations invited to mammography screening. There have been questions regarding the value of mammography in the era of modern therapies, and the relative contribution of mammography screening and modern therapy on mortality reduction. Aim: We have sought to clarify the extent to which early detection through mammography screening contributes to the reduction of breast cancer death in the era of modern adjuvant therapies. We address this question by studying five decades of continuous data from a stable population spanning the pre- and postscreening and adjuvant therapy periods. Methods: We analyzed changes in breast cancer mortality in a stable population in Dalarna County, Sweden, among women aged 40-69 years during the 52 years from 1964 through 2015. Mortality data were obtained from the National Cause of Death Register in Sweden, and incidence data from the Swedish National Cancer Registry. Crude and incidence-based mortality rates were compared among four successive 13-year periods: the prescreening period from 1964 through 1976, the Swedish Two-County randomized screening trial period from 1977 through 1989, and two service screening periods from 1990-2002 and from 2003-2015. Furthermore, we measured the effect of early detection upon breast cancer mortality in women exposed to mammography screening by comparison with breast cancer death in women not exposed to mammography screening, within these three screening periods. Data were analyzed by Poisson regression, with corrections for lead time and self-selection bias. Results: There were 5844 incident cases and 1425 breast cancer deaths during the 52 years of observation. The relative breast cancer mortality rates associated with exposure to screening, adjusted for self-selection bias, were 0.46 (95% CI 0.30-0.69) in the trial period (1977-1989), 0.44 (95% CI 0.30-0.65) in the 1990-2002 period, and 0.37 (95% CI 0.24-0.56) in the 2003-2015 period. The significant reductions in incidence-based breast cancer mortality associated with exposure to screening were independent of contemporaneous changes in therapy. Conclusion: The combination of early detection of breast cancer through mammography screening and the resultant earlier treatment has significantly reduced breast cancer mortality in Dalarna County in the women exposed to screening, compared with the women not participating in screening, by a factor of 2.2 in the screening trial period, increasing to a factor of 2.7 in the most recent service screening period. These mortality benefits can be attributed to the far greater effectiveness of modern therapeutic methods upon cancers detected at screening compared with the poorer effectiveness of the same therapeutic methods in women not participating in screening.

The effect of mammography screening regimen on incidence-based breast cancer mortality

Incidence-based mortality quantifies the distribution of cancer deaths and life-years lost, according to age at detection. We investigated the temporal distribution of the disease burden, and the effect of starting and stopping ages and interval between screening mammography examinations, on incidence-based mortality. Incidence-based mortality was estimated using an established breast cancer simulation model, adapted and validated to simulate breast cancer incidence, screening performance, and delivery of therapies in Canada. Ten strategies were examined, with varying starting age (40 or 50), stopping age (69 or 74), and interval (1, 2, 3 years), and "No Screening." Life-years lost were computed as the difference between model predicted time of breast cancer death and that estimated from life tables. Without screening, 70% of the burden in terms of breast cancer deaths extends between ages 45 and 75. The mean of the distribution of ages of detection of breast cancers that will be fatal in an unscreened population is 61.8 years, while the mean age of detection weighted by the number of life-years lost is 55, a downward shift of 6.8 years. Similarly, the mean age of detection for the distribution of life-years gained through screening is lower than that for breast cancer deaths averted. Incidence-based mortality predictions from modeling elucidate the age dependence of the breast cancer burden and can provide guidance for optimizing the timing of screening regimens to achieve maximal impact. Of the regimens studied, the greatest lifesaving effect was achieved with annual screening beginning at age 40.

Effect of organized mammography screening on breast cancer mortality: a population-based cohort study in Norway

Background Reviews of the randomized controlled trials (RCTs) of mammography screening conducted during the 1970s and 1980s reported a 15–21% reduction in breast cancer mortality. Improved cancer treatment and enhanced awareness may however have reduced the potential net benefit from mammography screening. New RCTs are no longer feasible and observational studies yield widely varying estimates of the reduced breast cancer mortality (0% to 43%), depending on study design. In Norway, mammography screening was introduced gradually during the period 1996–2004. Using this as a natural experiment, we aimed to estimate the effect of organized mammography screening on incidence-based breast cancer mortality by comparing changes in mortality among women eligible for screening to concurrent changes in younger and older ineligible women. The use of un-screened age-groups as control groups allowed us to conduct a balanced incidence-based mortality study in which we aimed to distinguish the screening effect on breast cancer mortality from the effect of the concomitantly established diagnostic centers, which may also have improved treatment. Methods In a national county-wise balanced, open-cohort study in Norway, we used birth cohorts (1896–1982) to construct three age groups in both the historical and screening period: women eligible for screening and younger or older women ineligible for screening. We included women diagnosed with breast cancer who died within the same age-period group during 1987–2010 (n = 4903). We estimated relative incidence-based mortality rate ratios (relative MRR) comparing temporal changes in eligible women to concurrent changes in ineligible women. Additionally, we conducted analyses comparing the change in eligible women to younger, ineligible women with either continued accrual and follow-up period (eligible women only) or continued follow-up period. Finally, we checked for unadjusted confounding in two negative control analyses expected to produce a null result (relative MRR = 1). First, we compared the mortality change in younger women to the concurrent change in older women. Second, we extended the study period to include the period 1987–2010 for all counties and repeated our analysis as if screening had been introduced at the midpoint of the actual pre-screening period and the actual screening period in each county, respectively. Results All three age groups experienced a reduction in mortality when screening was introduced, but the decrease among eligible women was about the same among ineligible women (relative MRR = 1.05, 95% CI: [0.94–1.18]). Varying the definition of follow-up yields similar results. The negative control analyses all had relative MRRs close to 1 (estimates ranged from 0.91 to 1.04 and with all 95% CIs overlapping 1). Conclusion Mammography screening was not associated with a larger breast cancer mortality reduction than that of women ineligible for mammography screening. Based on the negative control analyses we found limited uncontrolled confounding in the applied observational design.

Effect of population breast screening on breast cancer mortality to 2005 in England and Wales: A nested case-control study within a cohort of one million women.

Objectives To evaluate the effectiveness of the NHS breast screening programme (NHSBSP) on breast cancer mortality in England and Wales and to compare findings with a cohort analysis of the same underlying population. Methods A nested case-control study within a cohort of 959,738 women in England and Wales aged 49-64 who were eligible for routine NHSBSP screening during 1991-2005. Cases who died from breast cancer in 1991-2005 were matched to controls without breast cancer at the case diagnosis date and alive when the case died. Risk of breast cancer mortality associated with intention to screen (ITS) (7047 cases/28,188 controls) and screening attendance (4707 cases/9413 controls) was examined. Bias was minimised in accordance with currently advocated best practice. Odds ratios (ORs) were calculated using conditional logistic regression. Results were compared with findings from an incidence-based breast cancer mortality cohort analysis. Results ITS was associated with a 21% breast cancer mortality reduction (OR = 0.79, 95% confidence interval [CI]: 0.71-0.88, P < 0.001). Attendance ≤5 years before diagnosis was associated with a 47% reduction in breast cancer mortality after self-selection correction (OR = 0.53, 95% CI: 0.46-0.62, P < 0.001). Breast cancer mortality reduction associated with ITS was 21% in both the case-control and cohort analyses, but the impact of attendance was marginally greater in the case-control analysis (36% vs. 32%). Conclusions Case-control studies designed and analysed according to current best practice guidelines offer an effective means of evaluating population breast screening.

Breast Cancer Screening, Incidence, and Mortality Across US Counties.

Screening mammography rates vary considerably by location in the United States, providing a natural opportunity to investigate the associations of screening with breast cancer incidence and mortality, which are subjects of debate. To examine the associations between rates of modern screening mammography and the incidence of breast cancer, mortality from breast cancer, and tumor size. An ecological study of 16 million women 40 years or older who resided in 547 counties reporting to the Surveillance, Epidemiology, and End Results cancer registries during the year 2000. Of these women, 53,207 were diagnosed with breast cancer that year and followed up for the next 10 years. The study covered the period January 1, 2000, to December 31, 2010, and the analysis was performed between April 2013 and March 2015. Extent of screening in each county, assessed as the percentage of included women who received a screening mammogram in the prior 2 years. Breast cancer incidence in 2000 and incidence-based breast cancer mortality during the 10-year follow-up. Incidence and mortality were calculated for each county and age adjusted to the US population. Across US counties, there was a positive correlation between the extent of screening and breast cancer incidence (weighted r = 0.54; P < .001) but not with breast cancer mortality (weighted r = 0.00; P = .98). An absolute increase of 10 percentage points in the extent of screening was accompanied by 16% more breast cancer diagnoses (relative rate [RR], 1.16; 95% CI, 1.13-1.19) but no significant change in breast cancer deaths (RR, 1.01; 95% CI, 0.96-1.06). In an analysis stratified by tumor size, we found that more screening was strongly associated with an increased incidence of small breast cancers (≤2 cm) but not with a decreased incidence of larger breast cancers (>2 cm). An increase of 10 percentage points in screening was associated with a 25% increase in the incidence of small breast cancers (RR, 1.25; 95% CI, 1.18-1.32) and a 7% increase in the incidence of larger breast cancers (RR, 1.07; 95% CI, 1.02-1.12). When analyzed at the county level, the clearest result of mammography screening is the diagnosis of additional small cancers. Furthermore, there is no concomitant decline in the detection of larger cancers, which might explain the absence of any significant difference in the overall rate of death from the disease. Together, these findings suggest widespread overdiagnosis.

Comparative analysis of breast cancer mortality following mammography screening in Denmark and Norway

Denmark and Norway are the best countries to study effects of mammography screening, because they are the only countries with stepwise introduction of nationwide mammography screening, enabling comparative effectiveness studies of high quality. Although Denmark and Norway are countries with similar populations and health care systems, reported reductions in breast cancer mortality (incidence-based) caused by screening differed vastly; 25% in Denmark versus 10% in Norway. This study explores reasons for this difference. We compared two published studies from the Danish and Norwegian screening programs (Olsen et al., 2005; Kalager et al., 2010) investigating biennial mammography screening for women age 50-69 years. Four comparison groups of women were constructed ('current' and 'historical screening groups'; 'current' and 'historical nonscreening groups') based on county of residence. We calculated incidence-based breast cancer mortality in the current versus the historical period for screening and nonscreening groups, using mortality rate ratios (MRR) in the two countries, accounting for concomitant changes in breast cancer mortality. In the screening groups, similar reductions in breast cancer mortality were found when periods preceding and following start of screening were compared, in Denmark [25%; MRR 0.75; 95% confidence interval (CI) 0.64% to 0.88%] and in Norway (28%; MRR 0.72; 95% CI 0.63% to 0.81%). However, mortality increased in Denmark in the current nonscreening group compared with the historical nonscreening group; for women >59 years, breast cancer mortality increased by 14% (MRR 1.14, 95% CI 1.07-1.22), whereas in Norway a 19% reduction was seen (MRR 0.81, 95% CI 0.72-0.92). This increase accounts for the different relative effect of screening in Denmark and Norway; 25% breast cancer mortality reduction in Denmark, 10% in Norway. The seemingly larger effect of screening in Denmark may not be solely attributable to screening itself, but to increased breast cancer mortality in women older than 59 years not invited to screening.

E4. Current issues in breast cancer screening

E4. Current issues in breast cancer screening

Effects of annual vs triennial mammography interval on breast cancer incidence and mortality in ages 40–49 in Finland

Background:The aim of this study was to evaluate the effects of mammography screening invitation interval on breast cancer mortality in women aged 40–49 years.Methods:Since 1987 in Turku, Finland, women aged 40–49 years and born in even calendar years were invited for mammography screening annually and those born in odd years triennially. The female cohorts born during 1945–1955 were followed for up to 10 years for incident breast cancers and thereafter for an additional 3 years for mortality.Results:Among 14 765 women free of breast cancer at age 40, there were 207 incident primary invasive breast cancers diagnosed before the age of 50. Of these, 36 women died of breast cancer. The mean follow-up time for cancer incidence was 9.8 years and for mortality 12.8 years. The incidence of breast cancer was similar in the annual and triennial invitation groups (RR: 0.98, 95% confidence interval (CI): 0.75–1.29). Further, there were no significant differences in overall mortality (RR: 1.20, 95% CI: 0.99–1.46) or in incidence-based breast cancer mortality (RR: 1.14, 95% CI: 0.59–1.27) between the annual and triennial invitation groups.Conclusions:There were no differences in the incidence of breast cancer or incidence-based breast cancer mortality between the women who were invited for screening annually or triennially.

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

Self-selection bias is considered to be a problem when evaluating the effectiveness of breast cancer service screening in case-control studies. 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. 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. 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). 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.

Reduction in Breast Cancer Mortality from Organized Service Screening with Mammography: 1. Further Confirmation with Extended Data

In an earlier publication, our evaluation of data from breast cancer screening programs in seven Swedish counties suggested a 40% reduction in incidence-based breast cancer mortality among women actually screened. In the current study, we expand the previous analysis from seven counties to 13 large areas within nine counties, including six of the original counties and seven additional areas, examine a longer period of follow-up (20-44 years), apply new analytic methods for the evaluation of incidence-based breast cancer mortality, and estimate the number needed to screen to save one life. Data from six of the original counties (one being excluded as it does not yet have 10 years of follow-up after the initiation of screening), with increased follow-up, and seven additional large areas, within three counties, representing approximately 45% of Swedish women, provide information about age at diagnosis, age at death, and screening history for 542,187 women in the prescreening and 566,423 women in the screening epochs. Regardless of year of diagnosis, there were a total of 6,231 deaths due to breast cancer in the period of study as a whole. Of these, 4,778 were incidence-based deaths in the two epochs, i.e., death among cases diagnosed within either the prescreening or screening period. Data were analyzed using Poisson regression and adjusted, when necessary, for self-selection bias, contemporaneous changes in incidence, and changes in mortality independent of screening. Attendance was uniformly high, averaging 75% in the screening epochs. Recall rates for assessment varied from 4% to 5% at the first round of screening and approximately 3% at later rounds. Detection rates averaged five breast cancers per 1,000 women screened in the first round, and four breast cancers per 1,000 women screened in subsequent rounds. There was a significant 45% reduction in incidence-based breast cancer mortality among screened women in the screening epoch relative to incidence-based breast cancer mortality in the prescreening epoch (relative risk, 0.55; 95% confidence intervals, 0.51-0.59). After adjusting for self-selection bias, there still was a significant 43% reduction in incidence-based breast cancer mortality associated with screening (relative risk, 0.57; 95% confidence intervals, 0.53-0.62). These results indicate a reduction in breast cancer mortality of between 40% and 45% in association with screening, after adjustment for self-selection bias. These results were obtained with modest human costs: the number needed to screen to save one life was estimated as 472.

Reduction in Breast Cancer Mortality from the Organised Service Screening with Mammography: 2. Validation with Alternative Analytic Methods

In our companion article, incidence-based mortality analysis of data from breast cancer screening programs in 13 areas in Sweden indicated a 40% to 45% reduction in incidence-based breast cancer mortality among women actually screened. In this article, we apply new analytic methods for the evaluation of breast cancer mortality, using all breast cancer deaths in the period under study. Data were available from 13 areas on breast cancer mortality by year of diagnosis, year of death, and screening exposure. The period of study varied by area, the overall range of year of diagnosis being 1968 to 2001. We had data on 6,231 deaths and an average population of 555,676 women ages 40 to 69 years. Analysis of the effect of being screened was conducted using an alternative statistical analysis applied to all breast cancer deaths in the period of study, in addition to the incidence-based mortality analysis in our companion article. Data were analyzed using Poisson regression and adjusted for self-selection bias, contemporaneous changes in incidence, and changes in mortality independent of screening. Using all deaths in the period of observation, a significant 42% reduction in breast cancer mortality was observed, adjusting for contemporaneous changes independent of screening [relative risk (RR), 0.58; 95% confidence interval (95% CI), 0.53-0.62]. After further adjustment for self-selection bias, the mortality reduction was 39% (RR, 0.61; 95% CI, 0.55-0.68), also highly significant. These results indicate a reduction in breast cancer mortality of 39% in association with screening, after adjustment for contemporaneous changes and self-selection bias. These results confirm previous conclusions arrived at using incidence-based mortality analyses.