Breast cancer screening with mammography: overview of Swedish randomised trials. Outcome of screening by clinical examination of the breast in a trial in the Philippines. Effect of breast cancer screening after age 65. Long-term effects of mammography screening: updated overview of the Swedish randomised trials. Reduced breast cancer mortality in women under age 50: updated results from the Malmö Mammographic Screening Program. The Stockholm breast cancer screening trial--5-year results and stage at discovery. Canadian National Breast Screening Study: 2. Breast cancer detection and death rates among women aged 50 to 59 years. Informed choice in mammography screening: a randomized trial of a decision aid for 70-year-old women. Randomised controlled trial of the effect of evidence based information on women's willingness to participate in cervical cancer screening.
Despite encouraging results from screening trials the efficacy of mammography in reducing mortality remains somewhat controversial. Five studies have been done in Sweden. This overview, based on 282,777 women followed for 5-13 years in randomised trials in Malmö, Kopparberg, Ostergötland, Stockholm, and Gothenburg, reveals a 24% (95% confidence interval 13-34%) significant reduction of breast cancer mortality among those invited to mammography screening compared with those not invited. To avoid the potential risk of differential misclassification causes of death were assessed by an independent end-point committee after a blinded review of all fatal breast cancer cases. The mortality reduction was similar, irrespective of the end-point used for evaluation ("breast cancer as underlying cause of death" or "breast cancer present at death"). There was a consistent risk reduction associated with screening in all studies, although the point estimate of the relative risk for all ages varied non-significantly between 0.68 and 0.84. The cumulative breast cancer mortality by time since randomisation was estimated at 1.3 per 1000 within 6 years in the invited group compared with 1.6 in the control group. The corresponding figures after 9 years are 2.6 and 3.3 and after 12 years 3.9 and 5.1. The largest reduction of breast cancer mortality (29%) was observed among women aged 50-69 at randomisation. Among women 40-49 there was a non-significant 13% reduction. In this younger age group cumulative breast cancer mortality was similar in the invited and control group during the first 8 years of follow-up. After 8 years there was a difference in favour of the invited women. There was no evidence of any detrimental effect of screening in terms of breast cancer mortality in any age group. Among women aged 70-74 years screening seems to have had only a marginal impact. The value of screening by Clinical Examination of the Breast (CBE) as a means of reducing mortality from breast cancer (BC) is not established. The issue is relevant, as CBE may be a suitable option for countries in economic transition, where incidence rates are on the increase but limited resources do not permit screening by mammography. Our aims were to assess whether mass screening by CBE carried out by trained para-medical personnel is feasible in an urban population of a low-income country, and its efficacy in reducing BC mortality. Our study was designed as a randomised controlled trial of the effect on BC mortality of 5 annual CBE carried out by trained nurses. The target population was women aged 35-64 years, resident in 12 municipalities of the National Capital Region of Manila, Philippines. The units of randomization were the 202 health centres (HC) within the selected municipalities. During 1995 nurses and midwives were recruited and trained in performing CBE. The first round of screening took place in 1996-1997. The intervention however showed a refractory attitude of the population with respect to clinical follow-up and was discontinued after the completion of the first screening round. Cases of breast cancer occurring in the study population during 1996-1999 were identified by the 2 local population-based registries. In the single screening round 151,168 women were interviewed and offered CBE, 92% accepted (138,392), 3,479 were detected positive for a lump and referred for diagnosis. Of these only 1220 women (35%) completed diagnostic follow-up, whereas 42.4% actively refused further investigation even with home visits, and 22.5% were not traced. Of 53 cases that occurred among screen-positive women in the 2 years after CBE only 34 were diagnosed through the intervention. Eighty cases occurred among screen-negative women. The test sensitivity for CBE repeated annually was 53.2%. The actual sensitivity of the programme was 25.6% and positive predictive value 1%. Screen-detected cases were non-significantly less advanced than the others. Previous studies have shown that most breast cancer cases in the Philippines present at advanced stages and have an unfavourable outcome. Although CBE undertaken by health workers seems to offer a cost-effective approach to reducing mortality, the sensitivity of the screening programme in the real context was low. Moreover, in this relatively well-educated population, cultural and logistic barriers to seeking diagnosis and treatment persist and need to be addressed before any screening programme is introduced.
                Copyright 2005 Wiley-Liss, Inc. To assess the effect of mammographic screening for breast cancer in women aged 65 years or over.
                The Swedish two county trial of screening for breast cancer, in which 77,080 women aged 40-74 (21,925 aged 65-74) were randomly allocated to receive regular mammographic screening for breast cancer, and 55,985 women aged 40-74 (15,344 aged 65-74) were allocated to an unscreened control group.
                One group was screened every 33 months on average, except for those aged 40-49 at randomisation who were screened every 24 months. The control group was screened once at the conclusion of the trial. The main statistical analysis was the comparison of cumulative mortality with 13 years of follow up between the screened and control groups, in age groups 50-64 and 65-74, using Poisson regression. This was complemented by subsidiary analyses assessing the lead time, sensitivity, and predicted mortality from the size, node status, and grade of tumours diagnosed in the screened and control groups.
                In the age group 65-74 at randomisation there was a significant reduction in breast cancer mortality in the screened group, with a relative mortality of 0.68 and 95% confidence interval of 0.51 to 0.89. This was backed up by the results of the analyses of lead time, sensitivity, and tumour characteristics.
                Women aged 65 or more who are regularly screened can expect a reduced risk of dying from breast cancer. There has been much debate about the value of screening mammography. Here we update the overview of the Swedish randomised controlled trials on mammography screening up to and including 1996. The Kopparberg part of the Two-County trial was not available for the overview, but the continuation of the Malmö trial (MMST II) has been added. The article also contains basic data from the trials that have not been presented before. Methods The trials (n=247010, invited group 129750, control group 117260) have been followed up by record linkage to the Swedish Cancer and Cause of Death Registers. The relative risks (RR) for breast cancer death and mortality were calculated for the invited and the control groups. The trial-specific as well as the age-specific effects were analysed. RRs were calculated by the density method, with total person-time experience of the cohort by time interval of follow-up as a basis for estimating mortality rates. We calculated weighted RRs and 95% CI with the Mantel-Haenszel procedure.
                The median trial time-the time from randomisation until the first round was completed for the control group or if the control group was not invited, until end of follow-up-was 6.5 years (range 3.0-18.1). The median follow-up time, the time from randomisation, to the end of follow-up, was 15.8 years (5.8-20.2). There were 511 breast cancer deaths in 1864770 women-years in the invited groups and 584 breast cancer deaths in 1688440 women-years in the control groups, a significant 21% reduction in breast cancer mortality (RR=0.79, 95% CI 0.70-0.89). The reduction was greatest in the age group 60-69 years at entry (33%). Looking at 5-year age groups, there were statistically significant effects in the age groups 55-59, 60-64, and 65-69 years (RR=0.76, 0.68, and 0.69, respectively). There was a small effect in women 50-54 years at randomisation (RR=0.95). The benefit in terms of cumulative breast cancer mortality started to emerge at about 4 years after randomisation and continued to increase to about 10 years. Thereafter the benefit in absolute terms was maintained throughout the period of observation. The age-adjusted relative risk for the total mortality was 0.98 (0.96-1.00).
                The advantageous effect of breast screening on breast cancer mortality persists after long-term follow-up. The recent criticism against the Swedish randomised controlled trials is misleading and scientifically unfounded. This article provides additional follow-up data of two cohorts from the Malmö Mammographic Screening Trial (MMST). The first cohort, MMST I, contained 7,984 women under age 50 at entry into MMST who were born between 1927 and 1932. Half were assigned to a control group and were not invited for examination until four years after the code was broken in the MMST in 1988. The second cohort, MMST II, contained 17,786 women born between 1933 and 1945. Fifty four percent of these women were randomly invited to screening between 1978 and 1990. The remaining 46%--the control group--was invited to screening between 1991 and 1994. Nine screening rounds were completed in MMST I, and a mean of five rounds were completed in MMST II; the screening interval ranged from 18 to 24 months. The effect of screening on breast cancer mortality was assessed by pooling the two cohorts. At the end of follow-up--December 1993 for MMST I and December 1995 for MMST II--there was a statistically significant 36% reduction in breast cancer mortality in the intervention groups (relative risk = 0.64; 95% CI: 0.45-0.89; P = 0.009). A harm-benefit analysis showed, however, that for every two breast cancer deaths prevented, one clinically insignificant cancer was diagnosed; for each breast cancer death prevented, 63 cancer-free women had been called back for further examinations; and for every 20 lives saved, one radiation-induced breast cancer death may have occurred. Recommendations for screening must therefore weigh mortality benefits against these negative effects. In screening programmes it is important to assess a preliminary effectiveness of the screening method as soon as possible in order to forecast survival figures. In March 1981 a controlled single-view mammographic screening trial for breast cancer was started in the south of Stockholm. The population invited for screening mammography consisted of 40,000 women aged 40-64 years, and 20,000 women served as a well-defined control group. The main aim of the trial was to determine whether repeated mammographic screening could reduce the mortality in the study population (SP) compared to the control population (CP). The cumulative number of advanced mammary carcinomas in the screening and the control populations from the first five years of screening have shown a tendency towards more favourable stages in the screened population aged 40-64 years. A breakdown by age suggests an effect in age group 50-59 years, but not yet in age groups 40-49 and 60-64 years. When comparing the rates of stage II+ cancer, an increased number is found in the study group. As the total rate of breast cancer is higher in SP than in CP, there ought to be a concealed group of stage II+ cancers in the CP which makes the comparison biased. A new approach has been designed, where an estimation of the 'hidden' number of stage II+ cancers in CP is added to the clinically detected cases, and in this respect a comparison has shown a decrease in the cumulative number of advanced cancers in the SP in relation to the CP (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) To evaluate the efficacy of annual mammography over and above annual physical examination of the breasts and the teaching of breast self-examination among women aged 50 to 59 on entry.
                Individually randomized controlled trial.
                Fifteen urban centres in Canada with expertise in the diagnosis and treatment of breast cancer.
                Women with no history of breast cancer and no mammography in the previous 12 months were randomly assigned to undergo either annual mammography and physical examination (MP group) or annual physical examination only (PO group). The 39,405 women enrolled from January 1980 through March 1985 were followed for a mean of 8.3 years.
                Derived from the participants by initial and annual self-administered questionnaires, from the screening examinations, from the patients' physicians, from the provincial cancer registries and by record linkage to the Canadian National Mortality Data Base. Expert panels evaluated histologic and death data.
                Rates of referral from screening, rates of detection of breast cancer from screening and from community care, nodal status, tumour size and rates of death from all causes and from breast cancer.
                Over 85% of the women in each group attended the screening sessions after screen 1. The characteristics of the women in the two groups were similar. Compared with the Canadian population the participants were more likely to be married, have fewer children, have more education, be in a professional occupation, smoke less and have been born in North America. The rate of screen-detected breast cancer on first examination was 7.20 per 1000 in the MP group and 3.45 per 1000 in the PO group, more node-positive tumours were found in the MP group than in the PO group. At subsequent screens the detection rates were a little less than half the rates at screen 1. During years 2 through 5 the ratios of observed to expected cases of invasive breast cancer were 1.28 in the MP group and 1.18 in the PO group. Of the women with invasive breast cancer through to 7 years, 217 in the MP group and 184 in the PO group had no node involvement, 66 and 56 had one to three nodes involved, 32 and 34 had four or more nodes involved, and 55 and 46 had an unknown nodal status. There were 38 deaths from breast cancer in the MP group and 39 in the PO group. The ratio of the proportions of death from breast cancer in the MP group compared with those in the UC group was 0.97 (95% confidence interval 0.62 to 1.52). The survival rates were similar in the two groups. Women whose cancer had been detected by mammography alone had the highest survival rate.
                The study was internally valid, and there was no evidence of randomization bias. Screening with yearly mammography in addition to physical examination of the breasts detected considerably more node-negative, small tumours than screening with physical examination alone, but it had no impact on the rate of death from breast cancer up to 7 years' follow-up from entry. Many women who have participated in mammography screening are now approaching 70 years of age. These women are advised to consider both the benefits and harms of continuing to be screened. Doing so may be difficult for individual women, and there are no evaluated decision support tools to assist them.
                To assess the effect of a decision aid (DA) about whether to continue or stop mammography screening for women aged 70 years, a population-based, randomized controlled trial was conducted in New South Wales, Australia. Women aged 70 years who had regularly participated in mammography screening were eligible to participate in the trial. Women received a DA providing balanced, quantitative information or standard information available from the screening program. The main outcomes were the percentage of women making an informed choice about whether to continue or stop screening and the percentage of women participating in the screening.
                Women who received the DA (the intervention group) were better informed than the control group (mean increase in knowledge score out of 10, 2.62 for the intervention group vs 0.68 for the control group; P < .001), and a significantly greater percentage made an informed choice (73.5% vs 48.8%; P < .001). The DA did not increase anxiety and slightly reduced decisional conflict. There was no difference in the percentage of women who participated in screening within 1 month.
                This DA increased knowledge and assisted women to make an informed choice. It did not alter participation in screening. The DA is an effective way to assist women to make a decision about continuing mammography screening and seems to be a feasible intervention within a population screening program. To assess whether providing women with additional information on the pros and cons of screening, compared with information currently offered by the NHS, affects their intention to attend for screening.
                Randomised controlled trial. Participants were randomly assigned to receive either the control, (based on an NHS Cervical Screening Programme leaflet currently used), or the intervention leaflet (containing additional information on risks and uncertainties).
                Three general practices in Birmingham.
                300 women aged 20 to 64 attending the practices during a one month period.
                Intention to attend for screening. Main results: 283 women (94.3%) completed the study. Fewer women in the intervention (79%) than the control group (88%) expressed intention to have screening after reading the information leaflet (difference between groups 9.2%, 95% confidence intervals (CI) 3.2% to 21.7%). The crude odds ratio (OR) and 95% CI was 0.50 (0.26 to 0.97). After adjusting for other factors, the trend persisted (OR 0.60, 95% CI 0.28 to 1.29). Having a previous Pap smear was the only significant predictor of intention to have screening (adjusted OR 2.54, 95% CI 1.03 to 6.21). Subgroup analysis showed no intervention effect in intended uptake between women at higher and lower risk of cervical cancer (p=0.59).
                Providing women with evidence based information on the risks, uncertainties, and the benefits of screening, is likely to deter some, but not differentially those at higher risk.
If we assume that screening reduces breast cancer mortality by 15% and that overdiagnosis and overtreatment is at 30%, it means that for every 2000 women invited for screening throughout 10 years, one will avoid dying of breast cancer and 10 healthy women, who would not have been diagnosed if there had not been screening, will be treated unnecessarily. Furthermore, more than 200 women will experience important psychological distress including anxiety and uncertainty for years because of false positive findings. To help ensure that the women are fully informed before they decide whether or not to attend screening, we have written an evidence-based leaflet for lay people that is available in several languages on www.cochrane.dk. Because of substantial advances in treatment and greater breast cancer awareness since the trials were carried out, it is likely that the absolute effect of screening today is smaller than in the trials. Recent observational studies show more overdiagnosis than in the trials and very little or no reduction in the incidence of advanced cancers with screening.