- Email: [email protected]
1–11 Reduction in Breast Cancer Mortality From Organized Service Screening With Mammography: 1. Further Confirmation With Extended Data
DIAGNOSTIC IMAGING 1–11
Reduction in Breast Cancer Mortality From Organized Service Screening With Mammography: 1. Further Confirmation With Extended Data The Swedish Organised Service Screening Evaluation Group (Queen Mary Univ of London; et al) Cancer Epidemiol Biomarkers Prev 15:45-51, 2006
Background.—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. Methods.—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 ~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 selfselection bias, contemporaneous changes in incidence, and changes in mortality independent of screening. Results.—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 ~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 incidencebased 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, 0.530.62). Conclusions.—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. Many physicians may be unsure of the difference between efficacy and effectiveness, although they could probably make an educated guess. If your sense is that efficacy means that a medical intervention, such as screening mammography, produces
benefit under the ideal conditions of a clinical trial, whereas effectiveness means that screening mammography is also effective under the ordinary circumstances of clinical practice, then you guessed correctly.1 After the ability of screening mammography to reduce breast cancer mortality was proven in randomized clinical trials (RCTs) in the 1980s, many Scandinavian countries began in the 1990s to offer screening as a public health service. It then became important to demonstrate that the magnitude of benefits to the Swedish population was similar to that previously found in the RCT study groups. A RCT compares, for example, the difference in breast cancer mortality rates between a study group that is offered screening and a control group that is not offered screening. Aside from the opportunity to be screened, the study group should have no other relevant differences from the control group. Thus, it is difficult to design and conduct a RCT without bias. Service screening studies also compare breast cancer death rates, but usually those before the screening era vs those of the same population during the screening era. Although service screening studies are easier to conduct than RCTs, analyses of their results can be just as challenging, because they must consider temporal changes in breast cancer incidence, age shifts in the population, improvements in treatment over time, and of course, self-selection bias among women who agree to be screened. There have been many previously published reports on results from the Scandinavian Service Screening programs; however, this latest article
®
Breast Diseases: A Year Book Quarterly Vol 18 No 1 2007
37 37
from the Swedish Organised Service Screening Evaluation Group represents the largest to date, encompassing approximately 45% of the Swedish female population in the breast cancer age group who were offered screening. Overall, about 75% of these women agreed to be screened every 2 years. Breast cancer mortality was reduced 27% among the population offered screening. After accounting for the mentioned confounding factors, breast
1–12
Reduction in Breast Cancer Mortality From the Organised Service Screening With Mammography: 2. Validations With Alternative Analytic Methods The Swedish Organised Service Screening Evaluation Group (Queen Mary Univ of London; et al) Cancer Epidemiol Biomarkers Prev 15:52-56, 2006
Background.—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. Methods.—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 pop-
38 38
®
cancer deaths were reduced 40% to 45% among women actually screened. Although the success of the Swedish program is extremely impressive, there is still much more we can do to further reduce breast cancer mortality by early detection. We need to improve compliance; screen at shorter intervals; finetune mammography interpretation and technique; and investigate the addition of supplementary screening modalities such as computer-aided detection, digi-
tal tomosynthesis, breast computed tomography, magnetic resonance imaging, and ultrasonography.
ulation 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. Results.—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. Conclusions.—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.
In this paper, alternative analytic methods were used to estimate the reduction in breast cancer mortality among women attending service screening mammography in 13 areas of Sweden. Breast cancer deaths were initially calculated to be reduced by 42%. After adjustment for selfselection bias and the effects of treatment improvements and increased breast cancer awareness on stage at diagnosis, the mortality reduction from screening was 39%. Through modern screening mammography, we have clearly entered a new era in breast cancer control. I agree with the authors that most of the reduction in breast cancer deaths was due to screening rather than advances in treatment. However, my own perspective is that the benefits to our patients result from the cooperative efforts of surgeons, oncologists, and radiologists as well as primary care physicians who encourage their patients to be screened. For chemotherapy to affect mortality and not just survival, cancer must be detected early. Similarly, early detection becomes more effective as treatments are improved.
Breast Diseases: A Year Book Quarterly Vol 18 No 1 2007
S. A. Feig, MD
Reference 1. Institute of Medicine, National Research Council: Mammography and Beyond: Developing Technologies for the Early Detection of Breast Cancer. Washington, DC: National Academies Press, 2001.
S. A. Feig, MD
Reduction in Breast Cancer Mortality From Organized Service Screening With Mammography: 1. Further Confirmation With Extended Data The Swedish Organised Service Screening Evaluation Group (Queen Mary Univ of London; et al) Cancer Epidemiol Biomarkers Prev 15:45-51, 2006
Background.—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. Methods.—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 ~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 selfselection bias, contemporaneous changes in incidence, and changes in mortality independent of screening. Results.—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 ~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 incidencebased 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, 0.530.62). Conclusions.—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. Many physicians may be unsure of the difference between efficacy and effectiveness, although they could probably make an educated guess. If your sense is that efficacy means that a medical intervention, such as screening mammography, produces
benefit under the ideal conditions of a clinical trial, whereas effectiveness means that screening mammography is also effective under the ordinary circumstances of clinical practice, then you guessed correctly.1 After the ability of screening mammography to reduce breast cancer mortality was proven in randomized clinical trials (RCTs) in the 1980s, many Scandinavian countries began in the 1990s to offer screening as a public health service. It then became important to demonstrate that the magnitude of benefits to the Swedish population was similar to that previously found in the RCT study groups. A RCT compares, for example, the difference in breast cancer mortality rates between a study group that is offered screening and a control group that is not offered screening. Aside from the opportunity to be screened, the study group should have no other relevant differences from the control group. Thus, it is difficult to design and conduct a RCT without bias. Service screening studies also compare breast cancer death rates, but usually those before the screening era vs those of the same population during the screening era. Although service screening studies are easier to conduct than RCTs, analyses of their results can be just as challenging, because they must consider temporal changes in breast cancer incidence, age shifts in the population, improvements in treatment over time, and of course, self-selection bias among women who agree to be screened. There have been many previously published reports on results from the Scandinavian Service Screening programs; however, this latest article
®
Breast Diseases: A Year Book Quarterly Vol 18 No 1 2007
37 37
from the Swedish Organised Service Screening Evaluation Group represents the largest to date, encompassing approximately 45% of the Swedish female population in the breast cancer age group who were offered screening. Overall, about 75% of these women agreed to be screened every 2 years. Breast cancer mortality was reduced 27% among the population offered screening. After accounting for the mentioned confounding factors, breast
1–12
Reduction in Breast Cancer Mortality From the Organised Service Screening With Mammography: 2. Validations With Alternative Analytic Methods The Swedish Organised Service Screening Evaluation Group (Queen Mary Univ of London; et al) Cancer Epidemiol Biomarkers Prev 15:52-56, 2006
Background.—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. Methods.—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 pop-
38 38
®
cancer deaths were reduced 40% to 45% among women actually screened. Although the success of the Swedish program is extremely impressive, there is still much more we can do to further reduce breast cancer mortality by early detection. We need to improve compliance; screen at shorter intervals; finetune mammography interpretation and technique; and investigate the addition of supplementary screening modalities such as computer-aided detection, digi-
tal tomosynthesis, breast computed tomography, magnetic resonance imaging, and ultrasonography.
ulation 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. Results.—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. Conclusions.—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.
In this paper, alternative analytic methods were used to estimate the reduction in breast cancer mortality among women attending service screening mammography in 13 areas of Sweden. Breast cancer deaths were initially calculated to be reduced by 42%. After adjustment for selfselection bias and the effects of treatment improvements and increased breast cancer awareness on stage at diagnosis, the mortality reduction from screening was 39%. Through modern screening mammography, we have clearly entered a new era in breast cancer control. I agree with the authors that most of the reduction in breast cancer deaths was due to screening rather than advances in treatment. However, my own perspective is that the benefits to our patients result from the cooperative efforts of surgeons, oncologists, and radiologists as well as primary care physicians who encourage their patients to be screened. For chemotherapy to affect mortality and not just survival, cancer must be detected early. Similarly, early detection becomes more effective as treatments are improved.
Breast Diseases: A Year Book Quarterly Vol 18 No 1 2007
S. A. Feig, MD
Reference 1. Institute of Medicine, National Research Council: Mammography and Beyond: Developing Technologies for the Early Detection of Breast Cancer. Washington, DC: National Academies Press, 2001.
S. A. Feig, MD