Trends in advanced breast cancer incidence rates after implementation of a mammography screening program in a German population

BackgroundMammography screening programs (MSPs) aim to detect early-stage breast cancers in order to decrease the incidence of advanced-stage breast cancers and to reduce breast cancer mortality. We analyzed the time trends of advanced-stage breast cancer incidence rates in the target population before and after implementation of the MSP in a region of northwestern Germany.MethodsThe MSP in the Münster district started in October 2005. A total of 13,874 women with an incident invasive breast cancer (BC) was identified by the population-based epidemiological cancer registry between 2000 and 2013 in the target group 50–69 years. Multiple imputation methods were used to replace missing data on tumor stages (10.4%). The incidence rates for early-stage (UICC I) and advanced-stage (UICC II+) BC were determined, and Poisson regression analyses were performed to assess trends over time.ResultsThe incidence rates for UICC I breast cancers increased during the step-up introduction of the MSP and remained elevated thereafter. By contrast, after increasing from 2006 to 2008, the incidence rates of UICC II+ breast cancers decreased to levels below the pre-screening period. Significantly decreasing UICC II+ incidence rates were limited to the age group 55–69 years and reached levels that were significantly lower than incidence rates in the pre-screening period.DiscussionThe incidence rates of advanced-stage breast cancers decreased in the age groups from 55 years to the upper age limit for screening eligibility, but not in the adjacent age groups. The findings are consistent with MSP lead time effects and seem to indicate that the MSP lowers advanced-stage breast cancer rates in the target population.     

Trends in breast cancer mortality in Sweden before and after implementation of mammography screening

Background

Incidence-based mortality modelling comparing the risk of breast cancer death in screened and unscreened women in nine Swedish counties has suggested a 39% risk reduction in women 40 to 69 years old after introduction of mammography screening in the 1980s and 1990s.

Objective

We evaluated changes in breast cancer mortality in the same nine Swedish counties using a model approach based on official Swedish breast cancer mortality statistics, robust to effects of over-diagnosis and treatment changes. Using mortality data from the NordCan database from 1974 until 2003, we estimated the change in breast cancer mortality before and after introduction of mammography screening in at least the 13 years that followed screening start.

Results

Breast mortality decreased by 16% (95% CI: 9 to 22%) in women 40 to 69, and by 11% (95% CI: 2 to 20%) in women 40 to 79 years of age.

Discussion

Without individual data it is impossible to completely separate the effects of improved treatment and health service organisation from that of screening, which would bias our results in favour of screening. There will also be some contamination of post-screening mortality from breast cancer diagnosed prior to screening, beyond our attempts to adjust for delayed benefit. This would bias against screening. However, our estimates from publicly available data suggest considerably lower benefits than estimates based on comparison of screened versus non-screened women.     

Colorectal cancer screening: a new strategy for the demonstration of occult intestinal bleeding

The topic of colorectal cancer screening is discussed with special emphasis on its history and improvement of its methodology. The author's own results are evaluated in terms of international data published in literature in order to put forward his proposals for a new strategy. The devastating power and endemic character of colorectal cancers is stressed and the development of screening activities is recommended to accomplish within the frame of the complex health service.     

Twenty years after the Chernobyl accident: solid cancer incidence in various groups of the Ukrainian population

Several major international studies such as those performed on the A-bomb survivors, have shown a clear linkage between the exposure to ionizing radiation and the occurrence of various cancer types including leukemia. While these studies are mostly characterized by high dose rates, studies on populations exposed after the Chernobyl accident are in most cases characterized by low dose rates which are typical for occupational radiation protection. Here, data on more than 60,000 Ukrainian workers who participated in recovery operation works in Chernobyl in 1986–1987, more than 50,000 evacuees from the city of Prypyat and the 30 km zone, and about 360,000 residents of most contaminated territories are presented, which cover a period of observation from 1980 to 2004. For all cancers combined, statistically significant higher incidence rates than the national rates were found only for the recovery workers (standardized incidence ratio (SIR) 117.2%, 95% confidence interval: 114.1–120.3), while those for the other investigated groups were lower. In all groups under study a significant increase of thyroid cancer incidence rates has been registered. This increase appears to be associated, at least partly, with the fallout of radioiodine, and it was found not only in children, but also in adolescents and adults. For example, the most significant excess was found for male recovery workers corresponding to a factor of 8.0. It is important to keep in mind, however, that the contribution of confounding factors such as an intensified thyroid screening after the Chernobyl accident could not be quantified, in the present study. For female recovery workers there was also an excess of breast cancer over the national rates (SIR 190.6%; 95% confidence interval: 163.6–217.7%). An analysis of the two other groups (evacuees and residents of contaminated territories) gave controversial results: relative to the local standard there was a statistically significant excess, while comparison with the national level did not substantiate this conclusion.     

Colorectal cancer screening for average-risk North Americans: an economic evaluation

Background

Colorectal cancer (CRC) fulfills the World Health Organization criteria for mass screening, but screening uptake is low in most countries. CRC screening is resource intensive, and it is unclear if an optimal strategy exists. The objective of this study was to perform an economic evaluation of CRC screening in average risk North American individuals considering all relevant screening modalities and current CRC treatment costs.

Methods and Findings

An incremental cost-utility analysis using a Markov model was performed comparing guaiac-based fecal occult blood test (FOBT) or fecal immunochemical test (FIT) annually, fecal DNA every 3 years, flexible sigmoidoscopy or computed tomographic colonography every 5 years, and colonoscopy every 10 years. All strategies were also compared to a no screening natural history arm. Given that different FIT assays and collection methods have been previously tested, three distinct FIT testing strategies were considered, on the basis of studies that have reported “low,” “mid,” and “high” test performance characteristics for detecting adenomas and CRC. Adenoma and CRC prevalence rates were based on a recent systematic review whereas screening adherence, test performance, and CRC treatment costs were based on publicly available data. The outcome measures included lifetime costs, number of cancers, cancer-related deaths, quality-adjusted life-years gained, and incremental cost-utility ratios. Sensitivity and scenario analyses were performed. Annual FIT, assuming mid-range testing characteristics, was more effective and less costly compared to all strategies (including no screening) except FIT-high. Among the lifetimes of 100,000 average-risk patients, the number of cancers could be reduced from 4,857 to 1,782 and the number of CRC deaths from 1,393 to 457, while saving CAN$68 per person. Although screening patients with FIT became more expensive than a strategy of no screening when the test performance of FIT was reduced, or the cost of managing CRC was lowered (e.g., for jurisdictions that do not fund expensive biologic chemotherapeutic regimens), CRC screening with FIT remained economically attractive.

Conclusions

CRC screening with FIT reduces the risk of CRC and CRC-related deaths, and lowers health care costs in comparison to no screening and to other existing screening strategies. Health policy decision makers should consider prioritizing funding for CRC screening using FIT. Please see later in the article for the Editors'' Summary     

Incidence of breast cancer and estimates of overdiagnosis after the initiation of a population-based mammography screening program

Background:

There has been growing interest in the overdiagnosis of breast cancer as a result of mammography screening. We report incidence rates in British Columbia before and after the initiation of population screening and provide estimates of overdiagnosis.

Methods:

We obtained the numbers of breast cancer diagnoses from the BC Cancer Registry and screening histories from the Screening Mammography Program of BC for women aged 30–89 years between 1970 and 2009. We calculated age-specific rates of invasive breast cancer and ductal carcinoma in situ. We compared these rates by age, calendar period and screening participation. We obtained 2 estimates of overdiagnosis from cumulative cancer rates among women between the ages of 40 and 89 years: the first estimate compared participants with nonparticipants; the second estimate compared observed and predicted population rates.

Results:

We calculated participation-based estimates of overdiagnosis to be 5.4% for invasive disease alone and 17.3% when ductal carcinoma in situ was included. The corresponding population-based estimates were −0.7% and 6.7%. Participants had higher rates of invasive cancer and ductal carcinoma in situ than nonparticipants but lower rates after screening stopped. Population incidence rates for invasive cancer increased after 1980; by 2009, they had returned to levels similar to those of the 1970s among women under 60 years of age but remained elevated among women 60–79 years old. Rates of ductal carcinoma in situ increased in all age groups.

Interpretation:

The extent of overdiagnosis of invasive cancer in our study population was modest and primarily occurred among women over the age of 60 years. However, overdiagnosis of ductal carcinoma in situ was elevated for all age groups. The estimation of overdiagnosis from observational data is complex and subject to many influences. The use of mammography screening in older women has an increased risk of overdiagnosis, which should be considered in screening decisions.There is growing interest in the overdiagnosis of breast cancer resulting from mammography screening.^1,2 It has been suggested that incidence rates after the introduction of mammography screening are higher than would be expected from the early detection of clinically significant disease alone. The clinical importance of ductal carcinoma in situ has long been unclear, and recent attention has also focused on the potential overdiagnosis of invasive cancer.^1,3,4 Furthermore, more frequent screening, wider age ranges and higher false-positive rates in much of North America may result in increased overdiagnosis⁵ in comparison with Europe, the source of most reports.The Screening Mammography Program of BC provides bilateral 2-view mammography screening to female residents of British Columbia. The program began in 1988 at a single location and progressively expanded by adding centres in larger communities and extending mobile services; by 2000, geographic coverage was effectively 100%. Women aged 40–79 years are eligible to self-refer. Since 1997, women aged 40–49 years are reminded to return annually, and those over 50 years of age are reminded to return biennially. Women outside of this age-range can undergo screening with a physician’s referral. Rates of abnormal results on screening mammography in British Columbia are comparable to the community rates seen in the United States.⁶Our primary objective for this study was to estimate the extent of overdiagnosis of breast cancer due to screening. To do this, we examined cancer rates in the following subpopulations: all women 1970–1979, and women in 2005–2009 classified by active and nonactive participation in screening. From 1970 to 1979, screening was infrequent and no organized program existed. In the period 2005–2009, screening was well established and the use of hormone replacement therapy for menopause had declined.⁷ Our secondary objective was to determine the changes in population incidence of breast cancer, both invasive and ductal carcinoma in situ, following the implementation of a population-based screening program. Thus, we report an analysis of population age-specific incidence rates in British Columbia over a 40-year period (1970–2009).     

Neonatal screening for congenital adrenal hyperplasia in North-Eastern Italy: a report three years into the program

AIMS: To evaluate the incidence of congenital adrenal hyperplasia (CAH) in the Northern Italian population and the efficiency of the North-Eastern Italy screening program. To adjust cut-off levels for 17-hydroxyprogesterone (17-OHP) in relation to gestational age and birth weight, comparing the benefits in terms of reduction of recall rates with the two approaches and ultimately choosing the better of the two. SUBJECTS AND METHODS: Since September 2001, blood samples from neonates born in North-Eastern Italy have been screened with a fluoroimmunoassay method for 17-OHP determination (DELFIA). A preliminary cut-off level of > or = 30 nmol/l was set both for term and preterm newborns. The values of 17-OHP were analysed using statistical methods in relation to gestational age and birth weight in order to modify the cut-off on the basis of our data. RESULTS: After 33 months of screening we screened 128,282 newborns and detected 6 affected babies. During the first 8 months of screening among the recalled babies, 89.6 and 78.1% were preterm and low-birth-weight newborns, respectively, with a recall rate of 2.59% for premature neonates and of 4.94% for babies with birth weights < 2,500 g. We chose a new cut-off value of 50 nmol/l for preterm newborns only and, after 4 months, the recall rate was reduced to 0.83% for these infants and to 1.83% for low-birth-weight infants. CONCLUSION: After 33 months of screening for CAH in North-Eastern Italy, we report an incidence of 1:21,380. In 5 out of 6 affected babies, the diagnosis was established only after a positive screening test, which prevented a severe salt-wasting crisis in these babies. The cut-off level related to gestational age led to a significant reduction in the number of false-positives among preterm babies.We therefore intend to continue with the screening program for CAH in North-Eastern Italy, keeping a gestational-age-related cut-off in the hope that our data may encourage a national screening program for CAH.     

Sex Differences in Colorectal Cancer Survival: Population-Based Analysis of 164,996 Colorectal Cancer Patients in Germany

Risk of colorectal cancer (CRC) is considerably higher in men compared to women; however, there is inconclusive evidence of sex differences in CRC prognosis. We aimed to assess and explain sex differences in 5-year relative survival using standard and model-based period analysis among 164,996 patients diagnosed with CRC from 1997 to 2006 and reported to 11 German cancer registries covering a population of 33 million inhabitants. Age-adjusted 5-year relative survival was higher in women (64.5% vs. 61.9%, P<0.0001). A substantial survival advantage of women was confirmed in multivariate analysis after adjusting for CRC stage and subsite in subjects under 65 years of age (relative excess risk, RER 0.86, 95% CI 0.82–0.90), but not in older subjects (RER 1.01, 95% CI 0.98–1.04); this pattern was similar in the 1st and in the 2nd to 5th year after diagnosis. The survival advantage of women varied by CRC stage and age and was most pronounced for localized disease (RERs 0.59–0.88 in various age subgroups) and in patients under 45 years of age (RERs 0.59, 0.72 and 0.76 in patients with localized, regional or advanced disease, respectively). On the contrary, sex differences in survival did not vary by location of CRC. In conclusion, our large population-based study confirmed a survival advantage of female compared to male CRC patients, most notably in young and middle aged patients and patients with localized disease. The effect of sex hormones, either endogenous or through hormonal replacement therapy, might be the most plausible explanation for the observed patterns.     

Success of a program of routine prenatal screening for hepatitis B surface antigen: the first 2 years.

Prenatal screening for hepatitis B surface antigen (HBsAg) restricted to women with defined risk factors for chronic hepatitis B virus (HBV) infection fails to identify many carriers. A centralized program of routine HBsAg screening for all pregnant women in Alberta was introduced in 1985. We collected and analysed data for the first 2 years of the program in Edmonton to determine the frequency of risk factors for HBsAg positivity, the proportion of multiparous HBsAg-positive women not identified in previous pregnancies, the efficiency and cost-effectiveness of providing immunoprophylaxis to infants at risk of HBV infection and the degree of success in inducing adequate protection. A total of 149 women (158 pregnancies) were found to be HBsAg positive. Risk factors were readily ascertainable for 85% of the women; the remaining 15% would not have been identified through risk-selective screening. The most common risk factors were Oriental ethnic origin, history of hepatitis, jaundice or multiple transfusions of blood or blood products, and occupational exposure to blood. Although 86% of the multiparous HBsAg-positive women had risk factors, only 7% had been identified in previous pregnancies. The Alberta program appears to be cost-effective. We conclude that only routine prenatal screening will identify all infants at risk of perinatal HBV infection and that a comprehensive public health program involving central laboratories, private physicians and public health staff can be highly effective and efficient in protecting infants against hepatitis B.     

Transrectal sonography in prostate cancer detection--our 25 years experience of implementation

Prostate cancer is a leading public health problem of male population in developed countries. Gold standard for prostate cancer diagnosis is true cut biopsy guided by transrectal ultrasound. Aim of this study was to determine sensitivity, specificity, accuracy, positive and negative predictive value of transrectal sonography (TRUS) in prostate cancer detection. The analysis was made for two time periods, before and after routine implementation of prostate specific antigen (PSA) in prostate cancer diagnostics. From 1984 to 1993 TRUS guided prostate biopsy was performed in 564, and from 1994 to 2008 in 5678 patients. In the second period PSA was routinely used in prostate cancer diagnostics. In the first period by TRUS we have made an exact diagnosis of prostate cancer in 18.97% of patients what was confirmed by biopsy. 4.61% ware false positive and 11.34% ware false negative. In the second period prostate cancer was recognized in 30.34% of patients, confirmed by biopsy. False positive cases ware 6.11% and false negative 29.31%. Sensitivity of transrectal sonography in the first period was 62.57%, specificity 94.2%, accuracy 86.2%, positive predictive value 80.45% and negative predictive value 87.72%. In the second period sensitivity was 50.87%, specificity 91.93%, accuracy 73.84%, positive predictive value 83.24% and negative predictive value 70.39%. Based on our experience we can conclude that prostate cancer is mostly found in the peripheral zone. Smaller tumors are hypoechoic and bigger tumors are hyperechoic. Prostate cancer lesions are impossible to differentiate from chronic prostatitis only by TRUS. Implementation of PSA has significantly decrease sensitivity, accuracy and negative predictive value of TRUS in prostate cancer detection. TRUS guided true cut biopsy is a gold standard in prostate cancer diagnostics.     

Population prevalence of hereditary breast cancer phenotypes and implementation of a genetic cancer risk assessment program in southern Brazil

In 2004, a population-based cohort (the Núcleo Mama Porto Alegre - NMPOA Cohort) was started in Porto Alegre, southern Brazil and within that cohort, a hereditary breast cancer study was initiated, aiming to determine the prevalence of hereditary breast cancer phenotypes and evaluate acceptance of a genetic cancer risk assessment (GCRA) program. Women from that cohort who reported a positive family history of cancer were referred to GCRA. Of the 9218 women enrolled, 1286 (13.9%) reported a family history of cancer. Of the 902 women who attended GCRA, 55 (8%) had an estimated lifetime risk of breast cancer ≥ 20% and 214 (23.7%) had pedigrees suggestive of a breast cancer predisposition syndrome; an unexpectedly high number of these fulfilled criteria for Li-Fraumeni-like syndrome (122 families, 66.7%). The overall prevalence of a hereditary breast cancer phenotype was 6.2% (95%CI: 5.67-6.65). These findings identified a problem of significant magnitude in the region and indicate that genetic cancer risk evaluation should be undertaken in a considerable proportion of the women from this community. The large proportion of women who attended GCRA (72.3%) indicates that the program was well-accepted by the community, regardless of the potential cultural, economic and social barriers.     

Effect of screening on the incidence of cervical cancer in Alberta.

The rates of registration of cases of in-situ and invasive cancer of the cervix in Alberta have fallen for women aged 35 and over since the introduction of screening in the early 1960s, as predicted by theory and described in Finland. However, for women aged 15 to 34 years of age the predicted pattern was followed only initially: the registration rate for in-situ and probably also invasive cancer increased after 1973. This could be due to an actual increase in the incidence of in-situ cancer of the cervix among younger women, as might be expected from the epidemiologic aspects of the disease, but it might also be due to increased recruitment of younger women to the screening program.