Effect of screening mammography on the risk of breast cancer deaths and of all-cause deaths: a systematic review with meta-analysis of cohort studies.

OBJECTIVES: Observational cohort studies are used to evaluate the effectiveness of screening mammography in women offered screening. Because screening mammography has no effect on causes of death other than breast cancer (BC), cohort studies should show reductions in the risk of BC death substantially greater than possible reductions in the risk of all-cause death. We assessed the risk of BC deaths and of all-cause (or of nonBC) deaths associated with screening mammography attendance reported in cohort studies. STUDY DESIGN AND SETTING: Cohort studies published from 2002 to 2022 on women invited to screening mammography were searched in PubMed, Web of Sciences, Scopus, and in review articles. Random effect meta-analyses were performed using relative risks (RRs) of death between women who attended screening compared to women who did not attend screening. RESULTS: Eighteen cohort studies were identified, nine that reported RRs of BC deaths only, five that reported RRs of all-cause deaths only, and four that reported RRs for both BC deaths and all-cause deaths. The latter four cohort studies reported 12-76 times more all-cause deaths than BC deaths. The random-effect summary of RR for BC mortality in screening attendees vs nonattendees was 0.55 (95% CI: 0.50-0.60) in 13 cohort studies. The summary of RR for all-cause mortality was 0.54 (0.50-0.58) in 10 cohort studies. In the four cohort studies that evaluated both outcomes, the summary of RRs were 0.63 (0.43-0.83) for BC mortality and of 0.54 (0.44-0.64) for all-cause mortality. CONCLUSION: The similar relative reductions in breast- and all-cause (or nonBC) mortality indicates that screening mammography attendance is an indicator of characteristics associated with a lower risk of dying from any cause, including from BC, which observational studies have falsely interpreted as a screening effect.

Thyroid cancer overdiagnosis revisited.

BACKGROUND: Evidence has accumulated showing that an increase in thyroid cancer incidence reflects overdiagnosis of clinically unimportant lesions due to the rise in the use of neck ultrasonography. In the manuscript we examine the hypothesis that the rise in thyroid cancer incidence in Russia is largely caused by overdiagnosis. MATERIALS AND METHODS: Incidence and mortality rates of thyroid cancer for Russia overall and its administrative regions were abstracted from the statistical database of the Ministry of Health of Russia. For incidence trends, we calculated the percentage change, linear regression coefficient and p-value. The calculation of excess cases was based on expected age-specific distributions assuming that the incidence of thyroid cancer increases exponentially with age, as predicted by the multistage model of carcinogenesis. FINDINGS: Over the study period (1989-2015) the age standardized incidence of thyroid cancer has tripled in Russian women and doubled in men. Strong support for the hypothesis that the increase in thyroid cancer incidence may be artificial is evident from age-specific incidence trends: increases in incidence in middle age but not in older ages, thereby altering the age curves from the expected exponential shape to an "inverted U" shape. The number of observed cases of thyroid cancer exceeded the expected number by 138, 325 or 70 % of all cases diagnosed with thyroid cancer. We attribute the excess cases to detection by ultrasonography clinically unimportant lesions. This is supported by a very high incidence -to-mortality ratio, low case fatality, high and growing prevalence of thyroid cancer. CONCLUSION: Although there is an evidence that exposure to iodine 131 (131I) is an important cause of the increase in incidence of thyroid cancer in high-risk populations, we have shown that this increase could largely be attributed to overdiagnosis associated with ultrasonography screening. Overdiagnosis is the only explanation of the increase in thyroid cancer incidence in low-risk regions.

Maps and atlases of cancer mortality: a review of a useful tool to trigger new questions.

In this review we illustrate our view on the epidemiological relevance of geographically mapping cancer mortality. In the first part of this work, after delineating the history of cancer mapping with a view on interpretation of Cancer Mortality Atlases, we briefly illustrate the 'art' of cancer mapping. Later we summarise in a non-mathematical way basic methods of spatial statistics. In the second part of this paper, we employ the 'Atlas of Cancer Mortality in the European Union and the European Economic Area 1993-1997' in order to illustrate spatial aspects of cancer mortality in Europe. In particular, we focus on the cancer related to tobacco and alcohol epidemics and on breast cancer which is of particular interest in cancer mapping. Here we suggest and reiterate two key concepts. The first is that a cancer atlas is not only a visual tool, but it also contain appropriate spatial statistical analyses that quantify the qualitative visual impressions to the readers even though at times revealing fallacy. The second is that a cancer atlas is by no means a book where answers to questions can be found. On the contrary, it ought to be considered as a tool to trigger new questions.

Observed and Predicted Risk of Breast Cancer Death in Randomized Trials on Breast Cancer Screening.

BACKGROUND: The role of breast screening in breast cancer mortality declines is debated. Screening impacts cancer mortality through decreasing the number of advanced cancers with poor diagnosis, while cancer treatment works through decreasing the case-fatality rate. Hence, reductions in cancer death rates thanks to screening should directly reflect reductions in advanced cancer rates. We verified whether in breast screening trials, the observed reductions in the risk of breast cancer death could be predicted from reductions of advanced breast cancer rates. PATIENTS AND METHODS: The Greater New York Health Insurance Plan trial (HIP) is the only breast screening trial that reported stage-specific cancer fatality for the screening and for the control group separately. The Swedish Two-County trial (TCT)) reported size-specific fatalities for cancer patients in both screening and control groups. We computed predicted numbers of breast cancer deaths, from which we calculated predicted relative risks (RR) and (95% confidence intervals). The Age trial in England performed its own calculations of predicted relative risk. RESULTS: The observed and predicted RR of breast cancer death were 0.72 (0.56-0.94) and 0.98 (0.77-1.24) in the HIP trial, and 0.79 (0.78-1.01) and 0.90 (0.80-1.01) in the Age trial. In the TCT, the observed RR was 0.73 (0.62-0.87), while the predicted RR was 0.89 (0.75-1.05) if overdiagnosis was assumed to be negligible and 0.83 (0.70-0.97) if extra cancers were excluded. CONCLUSIONS: In breast screening trials, factors other than screening have contributed to reductions in the risk of breast cancer death most probably by reducing the fatality of advanced cancers in screening groups. These factors were the better management of breast cancer patients and the underreporting of breast cancer as the underlying cause of death. Breast screening trials should publish stage-specific fatalities observed in each group.

Statistical analyses in Swedish randomised trials on mammography screening and in other randomised trials on cancer screening: a systematic review.

OBJECTIVES: We compared calculations of relative risks of cancer death in Swedish mammography trials and in other cancer screening trials. PARTICIPANTS: Men and women from 30 to 74 years of age. SETTING: Randomised trials on cancer screening. DESIGN: For each trial, we identified the intervention period, when screening was offered to screening groups and not to control groups, and the post-intervention period, when screening (or absence of screening) was the same in screening and control groups. We then examined which cancer deaths had been used for the computation of relative risk of cancer death. MAIN OUTCOME MEASURES: Relative risk of cancer death. RESULTS: In 17 non-breast screening trials, deaths due to cancers diagnosed during the intervention and post-intervention periods were used for relative risk calculations. In the five Swedish trials, relative risk calculations used deaths due to breast cancers found during intervention periods, but deaths due to breast cancer found at first screening of control groups were added to these groups. After reallocation of the added breast cancer deaths to post-intervention periods of control groups, relative risks of 0.86 (0.76; 0.97) were obtained for cancers found during intervention periods and 0.83 (0.71; 0.97) for cancers found during post-intervention periods, indicating constant reduction in the risk of breast cancer death during follow-up, irrespective of screening. CONCLUSIONS: The use of unconventional statistical methods in Swedish trials has led to overestimation of risk reduction in breast cancer death attributable to mammography screening. The constant risk reduction observed in screening groups was probably due to the trial design that optimised awareness and medical management of women allocated to screening groups.