Radiation risk and mammographic screening of women from 40 to 49 years of age: effect on breast cancer rates and years of life

The aim of this study was to evaluate the carcinogenic risks associated with radiation in mass mammographic screening. Assessment was in terms of breast cancer mortality and years of life for a hypothetical cohort of 100 000 women. Data were obtained on incidence, mortality and life expectancy for the female population of Stockholm. With a screening interval of 18 months at ages 40-49 years, a total absorbed dose to the breast of 13 mGy per invited woman; and an annual breast cancer reduction of 25% per year 7 years from screening start, the net number of years gained was at least 2800. However, using the highest absorbed dose reported in routine mammographic screening in Sweden (approximately 3 mGy per view), and the highest reported radiation risk in the literature, a programme entailing annual screening with 2 views would require at least a 20% annual reduction in breast cancer mortality to give a net benefit in both the number of years of life gained and number of breast cancer deaths avoided. This observation supports the conclusion that exposures with low absorbed dose are essential when performing mass screening with mammography among young women.     

Breast cancer mortality after screening mammography in British Columbia women

Mammographic screening is a proven method for the early detection of breast cancer. The authors analyzed the impact of service mammographic screening on breast cancer mortality among British Columbia women who volunteered to be screened by the Screening Mammography Program of British Columbia. A cohort of women having at least one mammographic screen by Screening Mammography Program of British Columbia between the ages of 40 and 79 in the period 1988-2003 was identified. All cases and deaths from breast cancer occurring in British Columbia were identified from the British Columbia Cancer Registry and linked to the screening cohort. Expected deaths from breast cancer in the cohort were calculated using incidence and survival rates for British Columbia women not in the cohort. Adjustment was made for age and socioeconomic status of their area of residence at time of diagnosis. The breast cancer mortality ratio was calculated by dividing observed by expected breast cancer deaths. The mortality ratio (95% confidence interval) was 0.60 (0.55, 0.65) for all ages combined (p < 0.0001). The mortality ratio in women aged 40-49 at first screening was 0.61 (0.52, 0.71), similar to that in women over 50 (p = 0.90). Exclusion of mortality associated with breast cancers diagnosed after age 50 in women starting screening in their 40s increased the mortality ratio to 0.63 (0.52, 0.77), but it remained statistically significant. Correction for self-selection bias using estimates from the literature increased the mortality ratio for all ages to 0.76. Mammographic screening at all ages between 40 and 79 reduced subsequent mortality rates from breast cancer.     

Radiation risk associated with mammography screening examinations for women younger than 50 years of age

The target group of the German mammography screening program, conducted according to the European guidelines, is clearly defined: all women aged 50 to 69 years without evidence of breast cancer are invited to screening mammography every two years. In the present study the question was raised whether breast cancer screening by means of mammography is--from the point of view of radiation hygiene--justified also for women under 50 years of age. Based on current radio-epidemiological breast cancer studies, the excess lifetime risk (ELR) to incur or die from breast cancer of a 40, 45 and 50 year old woman was assessed. Different risk models were used to estimate the radiation risk, e.g. models given for the "Life Span Study" of the atomic bomb survivors and the risk model given in the recent Biological Effects of Ionizing Radiation (BEIR) VII report. The benefit risk ratio was defined as the ratio of the number of "saved lives" due to screening to the number of deaths due to "radiation induced breast cancer". All estimations were based on the assumption that screening is taking place up to the age of 69 years, with screening examinations being performed annually up to the age of 50 and every two years from the age of 50 onwards. The glandular dose per two-view mammography investigation was assumed to be 4 mGy. The benefit due to mammography screening was assumed to be 25% for all age groups. Assuming screening from the age of 40 or 45 years, the ELR of breast cancer is on average about 3.5 or 2 times as high compared to the ELR associated with screening starting from the age of 50 years. In comparison to the benefit risk ratio, which results for women participating in a mammography screening from the age of 50 years, the benefit risk ratio for women starting with screening already from the age of 40 or 45 years is reduced by a factor of 3 or 2. With the present data--with regard to both, the benefit and the radiation risk--it appears not to be justified to expose women from the age of 40 years to the additional radiation exposure associated with a mammography screening.     

Mammographic screening in BRCA1 mutation carriers postponed until age 40: Evaluation of benefits,costs and radiation risks using models

PurposeBRCA1 mutation carriers are offered screening with magnetic resonance imaging (MRI) and mammography. The aim of this study was to weigh benefits and risks of postponing mammographic screening until age 40.MethodsWith the MISCAN microsimulation model two screening protocols were evaluated: 1) the current Dutch guidelines: annual MRI from age 25–60, annual mammography from age 30–60, and biennial mammography in the nationwide program from age 60–74, and 2) the modified protocol: with annual mammography postponed until age 40. A cost-effectiveness analysis was performed.The risks of radiation-induced breast cancer mortality were estimated with absolute and relative exposure-risk models of the 7th Biological Effects of Ionising Radiation Committee.ResultsCurrent screening guidelines prevent 13,139 breast cancer deaths per 100,000 BRCA1 mutation carriers. Postponing mammography until age 40 would increase breast cancer deaths by 23 (0.17%), but would also reduce radiation-induced breast cancer deaths by 15 or 105 using the absolute and relative risk model respectively per 100,000 women screened. The estimated net effect is an increase of eight or a reduction of 82 breast cancer deaths per 100,000 women screened (depending on the risk model used). The incremental cost of mammograms between age 30–39 is €272,900 per life year gained.ConclusionsThe modified protocol may be slightly less effective or even better than the current guidelines. The high cost-savings justify a possible small loss of effectiveness.     

Quality-of-life effects of screening mammography in Norway

Mammography screening may save women from dying of breast cancer, although it has not been shown to reduce all-cause mortality. Screening also leads to overdiagnosis and many false positive mammograms aggravating women's quality-of-life. Quality adjusted life years (QALY) analyses of mammography screening have so far, calculated life years gained assuming that all prevented breast cancer deaths translate into a reduction in all-cause mortality. We calculated net QALYs in two hypothesized cohorts of 100,000 Norwegian women; one screened biennially from age 50 to 69 years and one not screened. We followed both cohorts to age 85 years. We used EQ-5D and an alternative equity weighted QALY instrument to estimate utility losses. In the screening cohort, we assumed 20% false positive tests during screening, different levels of overdiagnosis (20–75%) and different levels of breast cancer mortality reduction (10–30%). We assumed that reductions in breast cancer mortality only to a limited extent (20, 50 or 80%), resulted in reductions in all-cause mortality. We calculated both undiscounted and discounted (4%) QALYs. Assuming that 50% of the reduction in breast cancer mortality translated to a reduction in all-cause mortality and using estimated levels of benefits and harms in modern screening programs (50–75% overdiagnosis and 10% reduction in breast cancer mortality), undiscounted equity weighted QALY loss varied from 437 to 875 per 100,000 women. Using the levels of benefit and harms as reported in 30–40 years old randomized trials (30% overdiagnosis and 15% reduction in breast cancer mortality), undiscounted equity weighted QALY gain was 535 per 100,000. Net QALY in modern mammography screening in Norway is negative. Results could also be representative for Sweden, Denmark, UK and the US.     

Benefit‐to‐harm ratio of the Danish breast cancer screening programme

The primary aim of breast cancer screening is to reduce breast cancer mortality, but screening also has negative side‐effects as overdiagnosis. To evaluate a screening programme, both benefits and harms should be considered. Published estimates of the benefit‐to‐harm ratio, the number of breast cancer deaths prevented divided by the number of overdiagnosed breast cancer cases, varied considerably. The objective of the study was to estimate the benefit‐to‐harm ratio of breast cancer screening in Denmark. The numbers of breast cancer deaths prevented and overdiagnosed cases [invasive and ductal carcinoma in situ (DCIS)] were estimated per 1,000 women aged 50–79, using national published estimates for breast cancer mortality and overdiagnosis, and national incidence and mortality rates. Estimations were made for both invited and screened women. Among 1,000 women invited to screening from age 50 to age 69 and followed until age 79, we estimated that 5.4 breast cancer deaths would be prevented and 2.1 cases overdiagnosed, under the observed scenario in Denmark of a breast cancer mortality reduction of 23.4% and 2.3% of the breast cancer cases being overdiagnosed. The estimated benefit‐to‐harm ratio was 2.6 for invited women and 2.5 for screened women. Hence, 2–3 women would be prevented from dying from breast cancer for every woman overdiagnosed with invasive breast cancer or DCIS. The difference between the previous published ratios and 2.6 for Denmark is probably more a reflection of the accuracy of the underlying estimates than of the actual screening programmes. Therefore, benefit‐to‐harm ratios should be used cautiously.     

Evaluation of the organised mammographic screening programme in Australia.

An organised approach to mammographic screening in Australia commenced in 1992 as a free service for asymptomatic women in the target age range 50-69 years and accessible to all women aged >/=40 years. Screening is performed by two-view mammography, women aged 50-69 years being sent reminders every 2 years for repeat screens. National Accreditation Standards have been agreed and BreastScreen Australia has developed mechanisms to monitor and report performance including systems and standards for data collection. The national report includes participation rates, small cancer detection rates and programme sensitivities. These indicate that BreastScreen Australia is meeting its accreditation standards with respect to most measures. Routinely collected outcome data reflect an increasing trend in the proportion of women receiving breast conserving surgery; a decline in the proportion of women diagnosed with ductal carcinoma in situ undergoing axillary dissection and an increasing use of combination therapies with a corresponding decrease in the use of hormonal therapy alone. There have been increases in breast cancer incidence and falls in mortality with the largest changes in women aged 50-69 years. As the BreastScreen Australia database is routinely linked in future to population cancer registries, the mortality reduction due to mammographic screening may be estimated more precisely.     

Mammography in symptomatic and asymptomatic patients

It is now generally accepted that screening mammography at 1- to 3-year intervals can decrease mortality from breast cancer. Three randomized trials, involving a total of 238,000 women, have reported mortality results. In two trials (HIP and S2C), there was a significant reduction in breast cancer mortality (22 per cent at 18 years and 27 per cent at 8 years). One trial (M?lmo) showed a nonsignificant reduction in mortality at year 9 (5 per cent) and nonsignificant increases in mortality at earlier years. There are little data from randomized trials to support a benefit of mammographic screening in women under 50 years old. The two Swedish studies at last follow-up had 26 and 29 per cent more breast cancer deaths in young women in the group randomized to screening. The HIP study had 25 per cent fewer breast cancer deaths at 18 years in women under age 50 at the start of the trial, but because only 12 patients under age 50 had mammographically detectable tumors (out of 89 cancers diagnosed in the screened group), most of the benefit must be due to physical examinations or increased awareness of breast cancer symptoms. The as yet unpublished results of the Canadian trial in women under age 50 should elucidate the benefit of mammography in this age group. American centers report a malignant biopsy rate of 20 to 30 per cent for clinically occult lesions. This rate should increase as the proportion of women who have had prior mammography increases. High-quality mammography, including magnification technique for evaluation of suspicious lesions, proper localization and excisional biopsy techniques with pathologic correlation, and potentially, fine-needle aspiration, may improve the yield of screening mammography-induced open-biopsy procedures. Magnification technique can improve mammographic assessment of the extent of the tumor and guide re-excision for patients being considered for breast-conserving therapy. In the irradiated breast, in our experience, mammography alone detected 35 per cent of recurrent cancers in the irradiated breast. We recommend routine mammographic follow-up of the irradiated breast, including magnification of the local excision site, at 6 months, 1 year, and annually thereafter.     

Breast cancer in New South Wales in 1972-1995: tumor size and the impact of mammographic screening.

To examine the use of mammographic screening in women in New South Wales (NSW), we measured uptake of initial mammograms and estimated the proportions of breast cancers that were screen detected. To see if mammographic screening has been associated with reductions in advanced breast cancers and mortality from breast cancer, we analyzed trends in age-specific and age-standardized breast cancer incidence and mortality from 1972 to 1995 and tumor size in 1986, 1989, 1992 and April to September 1995. Between 1984 and the end of 1995, an estimated 72% of NSW women in their 50s and 67% in their 60s had had at least 1 mammogram and, in 1995, an estimated 39% of invasive breast cancers in women in these age groups were detected by mammography. Before 1989, breast cancer incidence increased only slightly (+1.3% annually) but then, from 1990 to 1995, increased more rapidly (+3.1% annually). Between 1986 and 1995, rates of small cancers (< 1 cm) increased steeply by 2.7 times in women 40-49 years of age and 5.6 times in women 50-69 years of age. The incidence of large breast cancers (3+ cm), after little apparent change to 1992, fell by 17% in women 40-49 years of age and 20% in those 50-69 years of age to 1995. Breast cancer mortality increased slightly between 1972 and 1989 (+0.5% annually) but then fell (-2.3% annually) from 1990 to 1995. We concluded that breast cancer rates had been influenced in expected directions by the introduction of mammographic screening in women resident in NSW. We expect that recent falls in incidence of larger breast cancers and breast cancer mortality will become steeper as screening coverage increases in the second half of the 1990s.     

Impact of screening mammography on mortality from breast cancer before age 60 in women 40 to 49 years of age

Background

Whether screening mammography programs should include women in their 40s is controversial. In Canada, screening of women aged 40–49 years has not been shown to reduce mortality from breast cancer. Given that screening mammography reduces mean tumour size and that tumour size is inversely associated with survival, the lack of benefit seen with screening is puzzling and suggests a possible adverse effect on mortality of mammography or subsequent treatment (or both) that counterbalances the expected benefit derived from downstaging.

Methods

We followed 50,436 women 40–49 years of age until age 60 for mortality from breast cancer. Of those women, one half had been randomly assigned to annual mammography and one half to no mammography. The impact of mammography on breast cancer mortality was estimated using a left-censored Cox proportional hazards model.

Results

Of 256 deaths from breast cancer recorded in the study cohort, 134 occurred in women allocated to mammography, and 122 occurred in those receiving usual care and not allocated to mammography. The cumulative risk of death from breast cancer to age 60 was 0.53% for women assigned to mammography and 0.48% for women not so assigned. The hazard ratio for breast cancer–specific death associated with 1 or more screening mammograms before age 50 was 1.10 (95% confidence interval: 0.86 to 1.40).

Conclusions

Mammography in women 40–49 years of age is associated with a small but nonsignificant increase in the risk of dying of breast cancer before age 60. Caution should be exercised when recommending mammographic screening to women before age 50.     

Breast cancer mortality with varying invitational policies in organised mammography

We examined the effect of different invitational policies on the reduction of breast cancer mortality at 60-79 years of age within the Finnish mammography programme in 1992-2003, which varied in its coverage at 60-69 years of age. The data from 260 municipalities were grouped into three categories: regular invitations at 50-59 years of age only, regular invitations at 50-69 years of age, and regular invitations at 50-59 years of age with irregular invitations at 60-69 years of age. Observed deaths from breast cancer were compared to those expected without screening among all women and among the screened and non-screened women. Observed deaths were obtained from population data and from a cohort follow-up in 1992-2003. Expected deaths were derived by modelling breast cancer mortality at population level in 1974-1985 and 1992-2003. The reduction in breast cancer mortality was strongest, 28% (0.72, 0.51-0.97), in municipalities with regular invitations at 50-69 years of age. No overall effect at 60-79 years of age was observed with regular invitations at 50-59 years of age. The study confirms a reduction by screening of breast cancer mortality in Finland. Uniform extension of invitations to 60-69 years of age would increase the number of prevented breast cancer deaths among the elderly.     

Breast cancer screening by mammography in Norway. Is it cost- effective?

Background: Mammography screening is a promising method for improving prognosis in breast cancer.Patients and methods: In this economic analysis, data from the Norwegian Mammography Project (NMP), the National Health Administration (NMA) and the Norwegian Medical Association (NMA) were employed in a model for cost-effectiveness analysis. According to the annual report of the NMP for 1996, 60,147 women aged 50–69 years had been invited to a two-yearly mammographic screening programme. 46,329 (77%) had been screened and 337 (0.7%) breast cancers had been revealed. The use of breast conserving surgery (BCS) was in this study estimated raised by 17% due to screening, the breast cancer mortality decreased by 30% and the number of life years saved per prevented breast cancer death was calculated 15 years.Results: The cost per woman screened was calculated £75.4, the cost per cancer detected £10,365 and the cost per life year (LY) saved £8,561. A raised frequency of BCS, diagnosis and adjuvant chemotherapy brought two years forward, follow-up costs and costs/savings due to prevented breast cancer deaths were all included in the analysis. A sensitivity analysis documented mammography screening cost-effective in Norway when four to nine years are gained per prevented breast cancer death.Conclusion: Mammography screening in Norway looks cost- effective. Time has come to encourage national screening programmes.     

Followup after 11 years – update of mortality results in the Stockholm mammographic screening trial

Results from several randomised mammography screening trials haveshown that it is possible to reduce mortalityin breast cancer by mammographic screening at leastfor women above 50 years of age. Thepurpose of this article is to present dataon mortality in breast cancer in study andcontrol groups of the Stockholm trial after 11years of followup, to analyse which age groupbenefits most from screening. In March 1981, 40,318women in Stockholm, aged 40 through 64 years,entered a randomized trial of breast cancer screeningby single view mammography alone, versus no interventionin a control group of 20 000 women.Two screening rounds were performed and the attendancerate was over 80% in the two rounds.During 1986 the control group was invited onceto screening. Totally 428 and 217 cases ofbreast cancer were diagnosed in the study andcontrol groups respectively. After a mean follow-up of11.4 years a nonsignificant mortality reduction of 26%was observed for the whole study group, witha relative risk (RR) of death in breastcancer of 0.74 (CI(confidence interval)=0.5–1.1). Forwomen aged 50–64 years a significant 38% mortalityreduction was observed with a RR of 0.62(CI=0.38–1.0). For women aged 40–49 yearsno effect on mortality was found, with aRR of death in breast cancer of 1.08(CI=0.54–2.17). The breakpoint for benefit inthis study seemed to be at 50 yearsof age when 5-year age groups were analysed,but this tendency is uncertain because of thelow statistical power in the analysis of theyounger age groups. Long screening intervals, the useof single-view mammography, and the fact that morethan 50% of the women in age group40–49 years were still below 50 years ofage when the study was closed, were allfacts that could have influenced the results inage group 40–49 years. Larger studies are neededto answer the question whether mammographic screening canbe successful in younger age groups.     

Mammographic screening after the age of 65 years: Evidence for a reduction in breast cancer mortality

We evaluated whether regular mammographic screening of women aged 65 years or older affected breast cancer mortality. In Nijmegen, a population-based screening program for breast cancer was started in 1975, with biennial mammography for women aged 35–64 years. Since 1977, elderly women have also been participating. For the present case-control study, women were selected who were over 64 years of age at the most recent invitation. Eighty-two of them had died from breast cancer. For these cases, 410 age-matched population controls were selected. The ratio of breast cancer mortality rates of the women who had participated regularly (i.e., in the 2 most recent screening rounds prior to diagnosis) vs. the women who had not participated in the screening was 0.56 (95% Cl = 0.28−1.13). The rate ratio was 0.45 in the women aged 65–74 years at the most recent invitation (95% Cl = 0.20−1.02), whereas it was 1.05 in the women aged 75 years and older (95% Cl = 0.27−4.14). While the breast cancer survival rate of the non-participant patients was fairly equal to that of patients from a control population, the underlying incidence rate of breast cancer was higher in the participants than in the no-participants. Therefore, we conclude that bias was present, but that it had decreased our effect estimate. The real reduction in breast cancer mortality due to regular screening will be even larger. Regular mammographic screening of women over age 65 (at least up to 75 years) can reduce breast cancer mortality by approximately 45%. © 1996 Wiley-Liss, Inc.     

The impact of organized mammography service screening on breast carcinoma mortality in seven Swedish counties

BACKGROUND: The evaluation of organized mammographic service screening programs is a major challenge in public health. In particular, there is a need to evaluate the effect of the screening program on the mortality of breast carcinoma, uncontaminated in the screening epoch by mortality from 1) cases diagnosed in the prescreening period and 2) cases diagnosed among unscreened women (i.e., nonattenders) after the initiation of organized screening. METHODS: In the current study, the authors ascertained breast carcinoma deaths in the prescreening and screening epochs in 7 Swedish counties from tumors diagnosed in these epochs and in the age group 40-69 years in 6 counties and 50-69 years in 1 county. Data regarding deaths were obtained from the Uppsala Regional Oncologic Center in conjunction with the National Cause of Death Register. The total number of women in the eligible age range living in each county was obtained from the annual population data of Statistics Sweden. Detailed screening data were provided by the screening centers in the seven counties, including the number of invited, the number attended, and whether each individual breast carcinoma case was exposed (screen-detected and interval cases combined) or unexposed (not-invited or nonattenders) to mammographic screening. There were 2044 breast carcinoma deaths from 14,092 incident tumors diagnosed in the prescreening and screening epochs, and the total number of person-years was 7.5 million. Data were analyzed using Poisson regression with corrections for self-selection bias and lead-time bias when appropriate. RESULTS: The mortality reduction for breast carcinoma in all 7 counties combined for women actually exposed to screening compared with the prescreening period was 44% (relative risk [RR] = 0.56; 95% confidence interval [95% CI], 0.50-0.62). When all incident tumors were considered, both those exposed and those unexposed to screening combined, counties with > 10 years of screening were found to demonstrate a significant 32% mortality reduction (RR = 0.68; 95% CI, 0.60-0.77) and counties with < or = 10 years of screening showed a significant 18% reduction in breast carcinoma mortality (RR = 0.82; 95% CI, 0.72-0.94) for the screening epoch compared with the prescreening epoch. Within the screening epoch, after adjustment for self-selection bias, a 39% mortality reduction (RR = 0.61; 95%CI, 0.55-0.68) was observed in association with invitation to screening. CONCLUSIONS: Organized service screening in 7 Swedish counties, covering approximately 33% of the population of Sweden, resulted in a 40-45% reduction in breast carcinoma mortality among women actually screened. The policy of offering screening is associated with a mortality reduction in breast carcinoma of 30% in the invited population, exposed and unexposed combined. The results of the current study indicate that the majority of the breast carcinoma mortality reduction is indeed due to the screening.     

Mammographic Screening of Women Attending a Reference Service Center in Southern Brazil

Background: To investigate the prevalence of and factors associated with performance of annual mammography by women above 40 years of age. Materials and Methods: This cross-sectional retrospective study was conducted at an oncology reference service in Southern Brazil from October 2013 to October 2014 with 525 women aged 40 years or older. Results: The prevalence of annual mammography was 54.1%; annual mammographic screening was performed for women without private medical insurance, who were under hormone replacement therapy and who had used contraception in the past. An association was found between non-performance of breast clinical and self-examination and non-performance of mammographic screening. Conclusions: Use of mammography for breast cancer screening in the public health care setting proved to be accessible; nevertheless, the proportion of screened women was low, and they exhibited poor adherence to the basic measures of care recommended for breast assessment. Thus, control of breast cancer requires implementing actions targeting the population most vulnerable to non-adherence to screening in addition to continuously monitoring and assessing that population to reduce the prevalence of this disease.     

Effect on breast cancer mortality of biennial mammographic screening of women under age 50

The effects on breast cancer mortality seen after 16 years of biennial screening of younger women are assessed in this prospective cohort study. Since 1975 some 13,500 women, aged 35—49 in 1975, were invited to participate in the Nijmegen screening programme comprising a mammographic examination every 2 years. By the end of 1990, 75 women had died of breast cancer out of the 332 cases diagnosed after the start of the screening project. Women from the same birth cohort, living in Arnhem, a neighbouring city with a comparable population and without a screening project, were used as controls. In this city, 74 breast cancer deaths out of 284 cases occurred during the same period. In Nijmegen, after 16 years of follow-up, breast cancer mortality showed a non-significant reduction of 6% (95% confidence interval: 32% reduction, 29% excess). In the relevant period, after a time lag of 10 years from the start of the programme, this reduction rose to 20% (95% confidence interval: 48% reduction, 23% excess). No reduction in breast cancer mortality was observed in the first decade of screening. For a later period, a shift towards a reduction emerges, but the data are as yet inconclusive. © 1995 Wiley-Liss. Inc.     

Modelling the overdiagnosis of breast cancer due to mammography screening in women aged 40 to 49 in the United Kingdom

Introduction

Overdiagnosis of breast cancer due to mammography screening, defined as the diagnosis of screen-detected cancers that would not have presented clinically in a women''s lifetime in the absence of screening, has emerged as a highly contentious issue, as harm caused may question the benefit of mammographic screening. Most studies included women over 50 years old and little information is available for younger women.

Methods

We estimated the overdiagnosis of breast cancer due to screening in women aged 40 to 49 years using data from a randomised trial of annual mammographic screening starting at age 40 conducted in the UK. A six-state Markov model was constructed to estimate the sensitivity of mammography for invasive and in situ breast cancer and the screen-detectable mean sojourn time for non-progressive in situ, progressive in situ, and invasive breast cancer. Then, a 10-state simulation model of cancer progression, screening, and death, was developed to estimate overdiagnosis attributable to screening.

Results

The sensitivity of mammography for invasive and in situ breast cancers was 90% (95% CI, 72 to 99) and 82% (43 to 99), respectively. The screen-detectable mean sojourn time of preclinical non-progressive and progressive in situ cancers was 1.3 (0.4 to 3.4) and 0.11 (0.05 to 0.19) years, respectively, and 0.8 years (0.6 to 1.2) for preclinical invasive breast cancer. The proportion of screen-detected in situ cancers that were non-progressive was 55% (25 to 77) for the first and 40% (22 to 60) for subsequent screens. In our main analysis, overdiagnosis was estimated as 0.7% of screen-detected cancers. A sensitivity analysis, covering a wide range of alternative scenarios, yielded a range of 0.5% to 2.9%.

Conclusion

Although a high proportion of screen-detected in situ cancers were non-progressive, a majority of these would have presented clinically in the absence of screening. The extent of overdiagnosis due to screening in women aged 40 to 49 was small. Results also suggest annual screening is most suitable for women aged 40 to 49 in the United Kingdom due to short cancer sojourn times.     

Cost‐effectiveness of digital mammography screening before the age of 50 in The Netherlands

In the Netherlands, routine mammography screening starts at age 50. This starting age may have to be reconsidered because of the increasing breast cancer incidence among women aged 40 to 49 and the recent implementation of digital mammography. We assessed the cost‐effectiveness of digital mammography screening that starts between age 40 and 49, using a microsimulation model. Women were screened before age 50, in addition to the current programme (biennial 50–74). Screening strategies varied in starting age (between 40 and 50) and frequency (annual or biennial). The numbers of breast cancers diagnosed, life‐years gained (LYG) and breast cancer deaths averted were predicted and incremental cost‐effectiveness ratios (ICERs) were calculated to compare screening scenarios. Biennial screening from age 50 to 74 (current strategy) was estimated to gain 157 life years per 1,000 women with lifelong follow‐up, compared to a situation without screening, and cost €3,376/LYG (3.5% discounted). Additional screening increased the number of LYG, compared to no screening, ranging from 168 to 242. The costs to generate one additional LYG (i.e., ICER), comparing a screening strategy to the less intensive alternative, were estimated at €5,329 (biennial 48–74 vs. current strategy), €7,628 (biennial 45–74 vs. biennial 48–74), €10,826 (biennial 40–74 vs. biennial 45–74) and €18,759 (annual 40–49 + biennial 50–74 vs. biennial 40–74). Other strategies (49 + biennial 50–74 and annual 45–49 + biennial 50–74) resulted in less favourable ICERs. These findings show that extending the Dutch screening programme by screening between age 40 and 49 is cost‐effective, particularly for biennial strategies.     

A meta‐analysis of mammographic screening with and without clinical breast examination

Mammographic screening with clinical breast examination has been recommended in Japan since 2000. Although mammographic screening without clinical breast examination has not been recommended, its introduction is anticipated. The efficacies of mammographic screening with and without clinical breast examination were evaluated based on the results of randomized controlled trials. PubMed and other databases for studies published between 1985 and 2014 were searched. The study design was limited to randomized controlled trials to evaluate mortality reduction from breast cancer. Five studies were eligible for meta‐analysis of mammographic screening without clinical breast examination. The relative risk for women aged 40–74 years was 0.75 (95% confidence interval, 0.67–0.83). Three studies evaluated the efficacy of mammographic screening with clinical breast examination. The relative risk for women aged 40–64 years was 0.87 (95% confidence interval, 0.77–0.98). The number needed to invite was always lower in mammographic screening without clinical breast examination than in mammographic screening with clinical breast examination. In both screening methods, the number needed to invite was higher in women aged 40–49 years than in women aged 50–70 years. These results suggest that mammographic screening without clinical breast examination can afford higher benefits to women aged 50 years and over. Although evidence of the efficacy of mammographic screening without clinical breast examination was confirmed based on the results of the randomized controlled trials, a Japanese study is needed to resolve local problems.