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1.  Effect on breast cancer screening response in The Netherlands of inviting women for an additional scientific investigation. 
STUDY OBJECTIVE--The study aimed to determine whether asking women to undertake an additional scientific study would deter them from attending screening for breast cancer. DESIGN--A randomised study was conducted in all women aged 50-70 years who were eligible for breast cancer screening and living in the city of Utrecht. A total of 1863 women were invited for mammography only and 1863 women were invited to participate in the European Prospective Investigation into Cancer and Nutrition (EPIC) in addition to the mammography. SUBJECTS--The study population comprised a random sample of 3726, 15% of the female population of Utrecht aged 50-70 years. MAIN RESULTS--The attendance rate for breast cancer screening was 53%, irrespective of the invitation to participate in the additional scientific study. CONCLUSIONS--Asking women to attend for an investigation in addition to the routine screening procedure for breast cancer did not affect the overall response to screening.
PMCID: PMC1059929  PMID: 8189174
2.  Misconceptions about efficacy of mammography screening: a public health dilemma 
OBJECTIVE—This study assessed accuracy of women's opinions about reduction in mortality from breast cancer attributable to mammography screening.
DESIGN—Cross sectional survey.
SETTING—General population of Geneva, Switzerland.
PARTICIPANTS—895 randomly selected women aged 40 to 80 years, free of breast cancer.
RESULTS—Women estimated the proportion of deaths from breast cancer that regular mammography screening prevents in women over age 50. Only 19.3% of the respondents assessed screening efficacy realistically (that is, reduction by about one fourth); 52.0% overestimated efficacy; 26.0% "didn't know", and 2.6% stated that screening prevents no death. Women who believed mammography screening to be effective had more positive attitudes toward screening (higher scores of pros and lower scores of cons) and were more likely to plan to have a mammogram (both p<0.001). Lack of opinion about the benefit of mammography screening was more common among women who had not consulted a gynaecologist recently (p=0.02) nor had had a mammogram during the past two years (p=0.009), who had no opinion about their risk of breast cancer (p<0.001), and who were 70 to 80 years old (p=0.04). Compared with women who provided realistic estimates of screening efficacy, those who overestimated efficacy believed to be at higher risk of breast cancer than other women (p=0.04) and were more likely to be Swiss nationals (p=0.001).
CONCLUSIONS—Most women overestimated and many were uninformed about the efficacy of mammography screening. Therefore, few women were able to take truly informed decisions about screening mammography.


Keywords: mammography screening; patient information; decision making
doi:10.1136/jech.55.11.799
PMCID: PMC1763315  PMID: 11604435
3.  Screening and self examination for breast cancer. 
BMJ : British Medical Journal  1994;309(6948):168-174.
Breast cancer is the major form of cancer in women, with nearly 30,000 new cases and over 15,000 deaths in the United Kingdom each year. Breast screening by mammography has been shown in randomised trials to reduce mortality from breast cancer in women aged 50 and over. An NHS breast screening programme has been in operation in the United Kingdom since 1988. Its aim is to reduce mortality from breast cancer by 25% in the population of women invited to be screened. The uptake of mammography among the eligible population may be the single most important determinant if the programme is to be effective. Primary care teams have an important part to play in encouraging women to attend for screening and in providing information, advice, and reassurance at all stages of the screening process. To date, routine breast self examination has not been shown to be an effective method of screening for breast cancer and should not therefore be promoted as a primary screening procedure. There is, however, a case to be made for women to become more "breast aware."
PMCID: PMC2540682  PMID: 8044097
4.  A case–control study of the impact of the East Anglian breast screening programme on breast cancer mortality 
British Journal of Cancer  2007;98(1):206-209.
Although breast cancer screening has been shown to work in randomised trials, there is a need to evaluate service screening programmes to ensure that they are delivering the benefit indicated by the trials. We carried out a case–control study to investigate the effect of mammography service screening, in the NHS breast screening programme, on breast cancer mortality in the East Anglian region of the UK. Cases were deaths from breast cancer in women diagnosed between the ages of 50 and 70 years, following the instigation of the East Anglia Breast Screening Programme in 1989. The controls were women (two per case) who had not died of breast cancer, from the same area, matched by date of birth to the cases. Each control was known to be alive at the time of death of her matched case. All women were known to the breast screening programme and were invited, at least once, to be screened. There were 284 cases and 568 controls. The odds ratio (OR) for risk of death from breast cancer in women who attended at least one routine screen compared to those who did not attend was 0.35 (CI: 0.24, 0.50). Adjusting for self-selection bias gave an estimate of the breast cancer mortality reduction associated with invitation to screening of 35% (OR=0.65, 95% CI: 0.48, 0.88). The effect of actually being screened was a 48% breast cancer mortality reduction (OR=0.52, 95% CI: 0.32, 0.84). The results suggest that the National Breast Screening Programme in East Anglia is achieving a reduction in breast cancer deaths, which is at least consistent with the results from the randomised controlled trials of mammographic screening.
doi:10.1038/sj.bjc.6604123
PMCID: PMC2359716  PMID: 18059396
breast cancer mortality; screening; case–control
5.  Screening Mammography for Women Aged 40 to 49 Years at Average Risk for Breast Cancer 
Executive Summary
Objective
The aim of this review was to determine the effectiveness of screening mammography in women aged 40 to 49 years at average risk for breast cancer.
Clinical Need
The effectiveness of screening mammography in women aged over 50 years has been established, yet the issue of screening in women aged 40 to 49 years is still unsettled. The Canadian Task Force of Preventive Services, which sets guidelines for screening mammography for all provinces, supports neither the inclusion nor the exclusion of this screening procedure for 40- to 49-year-old women from the periodic health examination. In addition to this, 2 separate reviews, one conducted in Quebec in 2005 and the other in Alberta in 2000, each concluded that there is an absence of convincing evidence on the effectiveness of screening mammography for women in this age group who are at average risk for breast cancer.
In the United States, there is disagreement among organizations on whether population-based mammography should begin at the age of 40 or 50 years. The National Institutes of Health, the American Association for Cancer Research, and the American Academy of Family Physicians recommend against screening women in their 40s, whereas the United States Preventive Services Task Force, the National Cancer Institute, the American Cancer Society, the American College of Radiology, and the American College of Obstetricians and Gynecologists recommend screening mammograms for women aged 40 to 49 years. Furthermore, in comparing screening guidelines between Canada and the United States, it is also important to recognize that “standard care” within a socialized medical system such as Canada’s differs from that of the United States. The National Breast Screening Study (NBSS-1), a randomized screening trial conducted in multiple centres across Canada, has shown there is no benefit in mortality from breast cancer from annual mammograms in women randomized between the ages of 40 and 49, relative to standard care (i.e. physical exam and teaching of breast-self examination on entry to the study, with usual community care thereafter).
At present, organized screening programs in Canada systematically screen women starting at 50 years of age, although with a physician’s referral, a screening mammogram is an insured service in Ontario for women under 50 years of age.
International estimates of the epidemiology of breast cancer show that the incidence of breast cancer is increasing for all ages combined, whereas mortality is decreasing, though at a slower rate. These decreasing mortality rates may be attributed to screening and advances in breast cancer therapy over time. Decreases in mortality attributable to screening may be a result of the earlier detection and treatment of invasive cancers, in addition to the increased detection of ductal carcinoma in situ (DCIS), of which certain subpathologies are less lethal. Evidence from the SEER cancer registry in the United States indicates that the age-adjusted incidence of DCIS has increased almost 10-fold over a 20-year period (from 2.7 to 25 per 100,000).
The incidence of breast cancer is lower in women aged 40 to 49 years than in women aged 50 to 69 years (about 140 per 100,000 versus 500 per 100,000 women, respectively), as is the sensitivity (about 75% versus 85% for women aged under and over 50, respectively) and specificity of mammography (about 80% versus 90% for women aged under and over 50, respectively). The increased density of breast tissue in younger women is mainly responsible for the lower accuracy of this procedure in this age group. In addition, as the proportion of breast cancers that occur before the age of 50 are more likely to be associated with genetic predisposition as compared with those diagnosed in women after the age of 50, mammography may not be an optimal screening method for younger women.
Treatment options vary with the stage of disease (based on tumor size, involvement of surrounding tissue, and number of affected axillary lymph nodes) and its pathology, and may include a combination of surgery, chemotherapy, and/or radiotherapy.
Surgery is the first-line intervention for biopsy confirmed tumours. The subsequent use of radiation, chemotherapy, or hormonal treatments is dependent on the histopathologic characteristics of the tumor and the type of surgery. There is controversy regarding the optimal treatment of DCIS, which is noninvasive.
With such controversy as to the effectiveness of mammography and the potential risk associated with women being overtreated or actual cancers being missed, and the increased risk of breast cancer associated with exposure to annual mammograms over a 10-year period, the Ontario Health Technology Advisory Committee requested this review of screening mammography in women aged 40 to 49 years at average risk for breast cancer. This review is the first of 2 parts and concentrates on the effectiveness of screening mammography (i.e., film mammography, FM) for women at average risk aged 40 to 49 years. The second part will be an evaluation of screening by either magnetic resonance imaging or digital mammography, with the objective of determining the optimal screening modality in these younger women.
Review Strategy
The following questions were asked:
Does screening mammography for women aged 40 to 49 years who are at average risk for breast cancer reduce breast cancer mortality?
What is the sensitivity and specificity of mammography for this age group?
What are the risks associated with annual screening from ages 40 to 49?
What are the risks associated with false positive and false negative mammography results?
What are the economic considerations if evidence for effectiveness is established?
The Medical Advisory Secretariat followed its standard procedures and searched these electronic databases: Ovid MEDLINE, EMBASE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews and the International Network of Agencies for Health Technology Assessment.
Keywords used in the search were breast cancer, breast neoplasms, mass screening, and mammography.
In total, the search yielded 6,359 articles specific to breast cancer screening and mammography. This did not include reports on diagnostic mammograms. The search was further restricted to English-language randomized controlled trials (RCTs), systematic reviews, and meta-analyses published between 1995 and 2005. Excluded were case reports, comments, editorials, and letters, which narrowed the results to 516 articles and previous health technology policy assessments.
These were examined against the criteria outlined below. This resulted in the inclusion of 5 health technology assessments, the Canadian Preventive Services Task Force report, the United States Preventive Services Task Force report, 1 Cochrane review, and 8 RCTs.
Inclusion Criteria
English-language articles, and English and French-language health technology policy assessments, conducted by other organizations, from 1995 to 2005
Articles specific to RCTs of screening mammography of women at average risk for breast cancer that included results for women randomized to studies between the ages of 40 and 49 years
Studies in which women were randomized to screening with or without mammography, although women may have had clinical breast examinations and/or may have been conducting breast self-examination.
UK Age Trial results published in December 2006.
Exclusion Criteria
Observational studies, including those nested within RCTs
RCTs that do not include results on women between the ages of 40 and 49 at randomization
Studies in which mammography was compared with other radiologic screening modalities, for example, digital mammography, magnetic resonance imaging or ultrasound.
Studies in which women randomized had a personal history of breast cancer.
Intervention
Film mammography
Comparators
Within RCTs, the comparison group would have been women randomized to not undergo screening mammography, although they may have had clinical breast examinations and/or have been conducting breast self-examination.
Outcomes of Interest
Breast cancer mortality
Summary of Findings
There is Level 1 Canadian evidence that screening women between the ages of 40 and 49 years who are at average risk for breast cancer is not effective, and that the absence of a benefit is sustained over a maximum follow-up period of 16 years.
All remaining studies that reported on women aged under 50 years were based on subset analyses. They provide additional evidence that, when all these RCTs are taken into account, there is no significant reduction in breast cancer mortality associated with screening mammography in women aged 40 to 49 years.
Conclusions
There is Level 1 evidence that screening mammography in women aged 40 to 49 years at average risk for breast cancer is not effective in reducing mortality.
Moreover, risks associated with exposure to mammographic radiation, the increased risk of missed cancers due to lower mammographic sensitivity, and the psychological impact of false positives, are not inconsequential.
The UK Age Trial results published in December 2006 did not change these conclusions.
PMCID: PMC3377515  PMID: 23074501
6.  The Edinburgh randomised trial of screening for breast cancer: description of method. 
British Journal of Cancer  1984;50(1):1-6.
Edinburgh was selected as one of the centres in the UK Seven-year Trial of Breast Screening of women aged 45-65 which began in 1979. Subsequently, our study was extended to a randomised trial with its own control population within the city. Half the practices were randomly allocated for screening, giving a cluster sampling of women. The total number in the trial is 65,000. Women with previously diagnosed breast cancer are excluded. Women allocated for screening are invited to the clinic and screened according to the procedures specified in the U.K. protocol, having clinical examination every year and mammography on alternate years. The two modalities of screening are assessed independently and the role of nurses is being evaluated. Breast cancer incidence is monitored by pathology register and the local cancer registry office and deaths from the General Register office. Long-term follow-up will be obtained through flagging at NHS Central Register. To determine the value of screening, standard statistical methods will be used to compare breast cancer mortality rates in the whole of the screening population with that of the controls. This trial has a power of 83% of detecting a reduction in mortality of 35% after 7 years of follow-up and a power of 95% of detecting a similar reduction at 10 years (alpha = 0.05, one-sided test).
PMCID: PMC1976924  PMID: 6743506
7.  By invitation only – the case for breast cancer screening reminders for women over 69 years 
Background
Breast cancer is the leading cause of cancer death in women in Australia. Early detection provides the best chance of reducing mortality and morbidity from the disease. Mammographic screening is a population health strategy for the early detection of breast cancer in Australia. Recruitment strategies such as regular advertising and biannual screening invitations are exclusively targeted at women aged 50 – 69 years. Even though they can participate, women 70 years or over are not invited or actively encouraged to undertake screening. Research has found that a routine letter of invitation increases the number of women participating in breast cancer screening.
Methods
Cancer data analysis and a literature and policy review was conducted to assess age specific breast cancer mortality rates and the legitimacy of rationale used to limit invitations for breast cancer screening to women younger than 70 years.
Results
The proportion of women over 69 years participating in the BreastScreen program is significantly less than rate of screening in the target age range (50–69 years). Evidence and data indicate that common justifications for limiting screening reminders to the target age range including life expectancy, comorbidities, effectiveness, treatment and cost are, for many women, unreasonable.
Conclusion
There is now sufficient data to support a change in the targeted upper age range for breast cancer screening to improve the existing suboptimal surveillance in women aged over 69 years.
doi:10.1186/1743-8462-5-23
PMCID: PMC2612671  PMID: 18990199
8.  Cost effectiveness of shortening screening interval or extending age range of NHS breast screening programme: computer simulation study 
BMJ : British Medical Journal  1998;317(7155):376-379.
Objective: To compare the cost effectiveness of two possible modifications to the current UK screening programme: shortening the screening interval from three to two years and extending the age of invitation to a final screen from 64 to 69.
Design: Computer simulation model which first simulates life histories for women in the absence of a screening programme for breast cancer and then assesses how these life histories would be changed by introducing different screening policies. The model was informed by screening and cost data from the NHS breast screening programme.
Setting: North West region of England.
Main outcome measures: Numbers of deaths prevented, life years gained, and costs.
Results: Compared with the current breast screening programme both modifications would increase the number of deaths prevented and the number of life years saved. The current screening policy costs £2522 per life year gained; extending the age range of the programme would cost £2612 and shortening the interval £2709 per life year gained. The marginal cost per life year gained of extending the age range of the screening programme is £2990 and of shortening the screening interval is £3545.
Conclusions: If the budget for the NHS breast screening programme were to allow for two more invitations per woman, substantial mortality reductions would follow from extending the age range screened or reducing the screening interval. The difference between the two policies is so small that either could be chosen.
Key messages Computer modelling suggested that the current breast screening programme in North West England will reduce total female breast cancer mortality by 12.8% Extending the programme to age 69 would reduce mortality by 16.4% at a marginal cost per life year saved of £2990 while reducing the interval to two years would reduce mortality by 15.3% at a marginal cost per life year saved of £3545 Extending the age range prevents more deaths from breast cancer but shortening the interval gains more life years If the budget for the NHS breast screening programme would allow for two more invitations per woman either of the two options could be chosen
PMCID: PMC28630  PMID: 9694752
9.  Breast cancer screening practices of safety net clinics: Results of a needs assessment study 
BMC Women's Health  2011;11:9.
Background
For low income and uninsured populations, safety net clinics are an important source of health care, including preventive services such as mammography screening. However, little is known about how well breast health is coordinated within the safety net clinic environment and what barriers patients encounter.
Methods
A needs assessment was conducted among eight community-based safety net clinics located in Montgomery County, Maryland to learn about breast cancer referral and screening procedures. Structured in-depth interviews were conducted with clinic staff during the summer of 2008.
Results
Safety net clinics reported that they routinely identified women who need mammography screening and referred women to mammography screening facilities. However, clinics were not aware of the limited number of free or low cost mammography screening slots available in the county or the waiting time to receive mammography services. Overall, screening barriers were common in the safety net system and only a few procedures were in place to help women overcome these barriers.
Conclusion
Safety net clinics face multiple barriers in providing and coordinating breast cancer screening services for low income or uninsured patients. These barriers prevent the efficient allocation of mammography screening services and prevent underserved women from accessing an important preventive health service.
doi:10.1186/1472-6874-11-9
PMCID: PMC3080315  PMID: 21457575
10.  Randomised controlled trial of mammographic screening in women from age 40: results of screening in the first 10 years 
British Journal of Cancer  2005;92(5):949-954.
Debate continues over the effectiveness of screening by mammography in women below age 50. We report here on results of screening in the first 10 years of a randomised trial to study the effect on breast cancer mortality of invitation to annual mammography from age 40 to 41 compared to first invitation to the 3-yearly UK national programme at age 50–52. The trial is taking place in 23 NHS breast screening centres. Between 1991 and 1997, 160 921 women were randomised in the ratio 1 : 2 to intervention and control arms. Screening is by two views at first screen and single view subsequently; data on screening up to and including round five are now complete. Uptake of invitation to screening is between 68 and 70% at all but the latest screening rounds. Rates of referral for assessment are 4.6% at first screen and 3.4% at subsequent screens. Invasive cancer detection rates are 0.09% at first screen, and similar at rescreens until the sixth and later screens. There is little evidence of regular mammography in the trial control arm. The setting of this trial within the NHS breast screening programme should ensure applicability of results to a national programme.
doi:10.1038/sj.bjc.6602396
PMCID: PMC2361899  PMID: 15726102
breast; screening; mammography; age; trial
11.  Breast cancer mortality with varying invitational policies in organised mammography 
British Journal of Cancer  2008;98(3):641-645.
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.
doi:10.1038/sj.bjc.6604203
PMCID: PMC2243161  PMID: 18231108
effectiveness; mammography; breast cancer; screening; policy; epidemiology
12.  Breast cancer mortality in Copenhagen after introduction of mammography screening: cohort study 
BMJ : British Medical Journal  2005;330(7485):220.
Objectives To evaluate the effect on breast cancer mortality during the first 10 years of the mammography service screening programme that was introduced in Copenhagen in 1991.
Design Cohort study.
Setting The mammography service screening programme in Copenhagen, Denmark.
Participants All women ever invited to mammography screening in the first 10 years of the programme. Historical, national, and historical national control groups were used.
Main outcome measures The main outcome measure was breast cancer mortality. We compared breast cancer mortality in the study group with rates in the control groups, adjusting for age, time period, and region.
Results Breast cancer mortality in the screening period was reduced by 25% (relative risk 0.75, 95% confidence interval 0.63 to 0.89) compared with what we would expect in the absence of screening. For women actually participating in screening, breast cancer mortality was reduced by 37%.
Conclusions In the Copenhagen programme, breast cancer mortality was reduced without severe negative side effects for the participants.
doi:10.1136/bmj.38313.639236.82
PMCID: PMC546064  PMID: 15649904
13.  Balancing harms and benefits of service mammography screening programs: a cohort study 
Introduction
The use of screening mammography is still under debate within the medical community. The aim of this study is to define a balance sheet of benefits (breast cancer mortality reduction) and harms (overdiagnosis) for mammography screening programs.
Methods
We compared breast cancer incidence and mortality in two cohorts of women, defined as 'attenders' or 'non-attenders' on the basis of the individual attitudes towards screening, who were invited to the first round of the Florentine screening program. The effects of screening exposure on breast cancer incidence and mortality were evaluated by fitting Poisson regression models adjusted for age at entry, marital status and deprivation index. We performed a sensitivity analysis excluding 34 women not responding to the invitation with a breast cancer diagnosis in the following six months.
Results
In total, we included 51,096 women aged 50 to 69 years invited at the first screening round (1991 to 1993) and followed-up for breast cancer incidence and mortality until 31 December 2007 and 31 December 2008, respectively The estimate of mortality reduction varies from 45% among 50 to 59 year-old women up to 51% among 60 to 69 year-old women. The estimate of overdiagnosis, according to the cumulative-incidence method, is an additional 10% of all breast cancer cases among 60 to 69 year-old women screened.
Conclusions
Comparing the breast cancer mortality and breast cancer incidence between attenders and non-attenders, we have determined that the overall cost to save one life corresponds to no more than one over-diagnosed tumor (from 0.6 to 1 depending on the selection criteria of the cohort), even if a residual self-selection bias cannot be excluded.
doi:10.1186/bcr3090
PMCID: PMC3496124  PMID: 22230345
14.  Comparison of breast and bowel cancer screening uptake patterns in a common cohort of South Asian women in England 
Background
Inequalities in uptake of cancer screening by ethnic minority populations are well documented in a number of international studies. However, most studies to date have explored screening uptake for a single cancer only. This paper compares breast and bowel cancer screening uptake for a cohort of South Asian women invited to undertake both, and similarly investigates these women's breast cancer screening behaviour over a period of fifteen years.
Methods
Screening data for rounds 1, 2 and 5 (1989-2004) of the NHS breast cancer screening programme and for round 1 of the NHS bowel screening pilot (2000-2002) were obtained for women aged 50-69 resident in the English bowel screening pilot site, Coventry and Warwickshire, who had been invited to undertake breast and bowel cancer screening in the period 2000-2002. Breast and bowel cancer screening uptake levels were calculated and compared using the chi-squared test.
Results
72,566 women were invited to breast and bowel cancer screening after exclusions. Of these, 3,539 were South Asian and 69,027 non-Asian; 18,730 had been invited to mammography over the previous fifteen years (rounds 1 to 5). South Asian women were significantly less likely to undertake both breast and bowel cancer screening; 29.9% (n = 1,057) compared to 59.4% (n = 40,969) for non-Asians (p < 0.001). Women in both groups who consistently chose to undertake breast cancer screening in rounds 1, 2 and 5 were more likely to complete round 1 bowel cancer screening. However, the likelihood of completion of bowel cancer screening was still significantly lower for South Asians; 49.5% vs. 82.3% for non-Asians, p < 0.001. South Asian women who undertook breast cancer screening in only one round were no more likely to complete bowel cancer screening than those who decided against breast cancer screening in all three rounds. In contrast, similar women in the non-Asian population had an increased likelihood of completing the new bowel cancer screening test. The likelihood of continued uptake of mammography after undertaking screening in round 1 differed between South Asian religio-linguistic groups. Noticeably, women in the Muslim population were less likely to continue to participate in mammography than those in other South Asian groups.
Conclusions
Culturally appropriate targeted interventions are required to reduce observed disparities in cancer screening uptakes.
doi:10.1186/1472-6963-10-103
PMCID: PMC2867962  PMID: 20423467
15.  What is the point: will screening mammography save my life? 
Background
We analyzed the claim "mammography saves lives" by calculating the life-saving absolute benefit of screening mammography in reducing breast cancer mortality in women ages 40 to 65.
Methods
To calculate the absolute benefit, we first estimated the screen-free absolute death risk from breast cancer by adjusting the Surveillance, Epidemiology and End Results Program 15-year cumulative breast cancer mortality to account for the separate effects of screening mammography and improved therapy. We calculated the absolute risk reduction (reduction in absolute death risk), the number needed to screen assuming repeated screening, and the survival percentages without and with screening. We varied the relative risk reduction from 10%–30% based on the randomized trials of screening mammography. We developed additional variations of the absolute risk reduction for a screening intervention, including the average benefit of a single screen, as well as the life-saving proportion among patients with earlier cancer detection.
Results
Because the screen-free absolute death risk is approximately 1% overall but rises with age, the relative risk reduction from repeated screening mammography is about 100 times the absolute risk reduction between the starting ages of 50 and 60. Assuming a base case 20% relative risk reduction, repeated screening starting at age 50 saves about 1.8 (overall range, 0.9–2.7) lives over 15 years for every 1000 women screened. The number needed to screen repeatedly is 1000/1.8, or 570. The survival percentage is 99.12% without and 99.29% with screening. The average benefit of a single screening mammogram is 0.034%, or 2970 women must be screened once to save one life. Mammography saves 4.3% of screen-detectable cancer patients' lives starting at age 50. This means 23 cancers must be found starting at age 50, or 27 cancers at age 40 and 21 cancers at age 65, to save one life.
Conclusion
The life-saving absolute benefit of screening mammography increases with age as the absolute death risk increases. The number of events needed to save one life varies depending on the prospective screening subset or reference class. Less than 5% of women with screen-detectable cancers have their lives saved.
doi:10.1186/1472-6947-9-18
PMCID: PMC2670293  PMID: 19341448
16.  Increasingly strong reduction in breast cancer mortality due to screening 
British Journal of Cancer  2011;104(6):910-914.
Background:
Favourable outcomes of breast cancer screening trials in the 1970s and 1980s resulted in the launch of population-based service screening programmes in many Western countries. We investigated whether improvements in mammography and treatment modalities have had an influence on the effectiveness of breast cancer screening from 1975 to 2008.
Methods:
In Nijmegen, the Netherlands, 55 529 women received an invitation for screening between 1975 and 2008. We designed a case–referent study to evaluate the impact of mammographic screening on breast cancer mortality over time from 1975 to 2008. A total number of 282 breast cancer deaths were identified, and 1410 referents aged 50–69 were sampled from the population invited for screening. We estimated the effectiveness by calculating the odds ratio (OR) indicating the breast cancer death rate for screened vs unscreened women.
Results:
The breast cancer death rate in the screened group over the complete period was 35% lower than in the unscreened group (OR=0.65; 95% CI=0.49–0.87). Analysis by calendar year showed an increasing effectiveness from a 28% reduction in breast cancer mortality in the period 1975–1991 (OR=0.72; 95% CI=0.47–1.09) to 65% in the period 1992–2008 (OR=0.35; 95% CI=0.19–0.64).
Conclusion:
Our results show an increasingly strong reduction in breast cancer mortality over time because of mammographic screening.
doi:10.1038/bjc.2011.44
PMCID: PMC3065280  PMID: 21343930
breast cancer; breast cancer mortality; screening; case–referent study
17.  Rate of over-diagnosis of breast cancer 15 years after end of Malmö mammographic screening trial: follow-up study 
BMJ : British Medical Journal  2006;332(7543):689-692.
Objective To evaluate the rate of over-diagnosis of breast cancer 15 years after the end of the Malmö mammographic screening trial.
Design Follow-up study.
Setting Malmö, Sweden.
Subjects 42 283 women aged 45-69 years at randomisation.
Interventions Screening for breast cancer with mammography or not (controls). Screening was offered at the end of the randomisation design to both groups aged 45-54 at randomisation but not to groups aged 55-69 at randomisation.
Main outcome measures Rate of over-diagnosis of breast cancer (in situ and invasive), calculated as incidence in the invited and control groups, during period of randomised design (period 1), during period after randomised design ended (period 2), and at end of follow-up.
Results In women aged 55-69 years at randomisation the relative rates of over-diagnosis of breast cancer (95% confidence intervals) were 1.32 (1.14 to 1.53) for period 1, 0.92 (0.79 to 1.06) for period 2, and 1.10 (0.99 to 1.22) at the end of follow-up.
Conclusion Conclusions on over-diagnosis of breast cancer in the Malmö mammographic screening trial can be drawn mainly for women aged 55-69 years at randomisation whose control groups were never screened. Fifteen years after the trial ended the rate of over-diagnosis of breast cancer was 10% in this age group.
doi:10.1136/bmj.38764.572569.7C
PMCID: PMC1410836  PMID: 16517548
18.  Mammographic screening before age 50 years in the UK: comparison of the radiation risks with the mortality benefits 
British Journal of Cancer  2005;93(5):590-596.
Mammographic screening before age 50 years is less effective than at older ages and the associated radiation risks are higher. We estimated how many breast cancer deaths could be caused and how many could be prevented by a decade of annual two-view mammographic screening starting at ages 20, 30 and 40 years, respectively, in the UK; for all women, and for women with first-degree relatives affected with breast cancer. We extrapolated from a radiation risk model to estimate the number of radiation-induced breast cancer deaths, and used results from randomised trials, which suggest a reduction in breast cancer mortality of 10–20% in women invited to screening before age 50 years, to estimate the number of deaths that could be prevented. The net change in breast cancer deaths was defined as the number of radiation-induced deaths minus the number of prevented deaths. For all women, assuming a reduction in mortality from screening of 20%, a decade of annual screening was estimated to induce more deaths than it prevents if started at age 20 years and at age 30 years (net increase=0.86 and 0.37 breast cancer deaths, respectively, per 1000 women screened). The corresponding estimate for screening starting at age 40 years was a net decrease of 0.46 deaths/1000 women screened and a zero net change assuming a 10% mortality reduction. Results for women with first-degree relatives with breast cancer were generally in the same direction but, because their background incidence rates are higher, the net increases or decreases were greater. In conclusion, our estimates suggest that a decade of annual two-view mammographic screening before age 40 years would result in a net increase in breast cancer deaths, and that starting at age 40 years could result in a material net decrease only if breast cancer mortality is reduced by about 20% or more in women screened. Although these calculations were based on a number of uncertain parameters, in general, the conclusions were not altered when these parameters were varied within a feasible range.
doi:10.1038/sj.bjc.6602683
PMCID: PMC2361593  PMID: 16136033
mammography; breast cancer; radiation; risk assessment
19.  Increasing Breast and Cervical Cancer Screening in Low-Income Women 
OBJECTIVE
To determine if women would have higher breast and cervical cancer screening rates if lay health advisers recommended screening and offered a convenient screening opportunity.
DESIGN
Controlled trial.
SETTING
Urban county teaching hospital.
PARTICIPANTS
Women aged 40 years and over attending appointments in several non-primary-care outpatient clinics.
INTERVENTIONS
Lay health advisers assessed the participants' breast and cervical cancer screening status and offered women in the intervention group who were due for screening an appointment with a female nurse practitioner.
MEASUREMENTS AND MAIN RESULTS
Screening rates at baseline and at follow-up 1 year after the intervention were determined. At follow-up, the mammography rate was 69% in the intervention group versus 63% in the usual care group (p = .009), and the Pap smear rate was 70% in the intervention group versus 63% in the usual care group (p = .02). In women who were due for screening at baseline, the mammography rate was 60% in the intervention group versus 50% in the usual care group (p = .006), and the Pap smear rate was 63% in the intervention group versus 50% in the usual care group (p = .002). The intervention was effective across age and insurance payer strata, and was particularly effective in Native American women.
CONCLUSIONS
Breast and cervical cancer screening rates were improved in women attending non-primary-care outpatient clinics by using lay health advisers and a nurse practitioner to perform screening. The effect was strongest in women in greatest need of screening.
doi:10.1046/j.1525-1497.1998.00161.x
PMCID: PMC1496995  PMID: 9734787
mass screening; vaginal smears; mammography; nurse practitioners; community health aides
20.  Effect on attendance at breast cancer screening of adding a self administered questionnaire to the usual invitation to breast screening in southern England 
STUDY OBJECTIVE: The primary aim of the research described in this paper was to ascertain whether inclusion of a self administered questionnaire with the usual invitation to routine breast screening affected screening uptake. Secondary aims included establishing appropriate questionnaire distribution and collection methods within the framework of the National Health Service Breast Screening Programme and optimisation of questionnaire design. DESIGN: Randomised study. SETTING: Oxfordshire and West of London Breast Screening Units. PARTICIPANTS/METHODS: 6400 women invited for routine screening mammography were individually randomised to receive either the usual breast screening invitation alone, or to receive the usual invitation accompanied by a self administered questionnaire, to be returned at the time of screening. Participants were then followed up and attendance rates at screening were compared between groups. MAIN RESULTS: Screening attendance rates were similar in women who did and did not receive a questionnaire (71% in each group). Of those who were sent a questionnaire and attended for screening, 77% returned a completed questionnaire. Screening uptake was not affected by the way in which the questionnaire was returned or by whether or not personal details and signed permission for follow up were requested. CONCLUSIONS: The inclusion of a self administered questionnaire accompanying the invitation to breast screening did not adversely affect screening uptake. A high proportion of women completed the questionnaire.
 
PMCID: PMC1756668  PMID: 9578859
21.  Should breast cancer survivors be excluded from, or invited to, organised mammography screening programmes? 
Background
The prevalence of breast cancer in developed countries has steadily risen over recent decades. Immediate and long-term health needs of patients, including preventive care and screening services, are receiving increasing attention. A question still unresolved is whether breast cancer survivors should receive mammographic surveillance in the clinical or screening setting and, thus, whether they should be excluded from, or invited to, organised mammography screening programmes. The objective of this article is to discuss the many contradictory aspects of this matter.
Discussion
Problems with mammographic surveillance of breast cancer survivors include: weak evidence of a reduction in mortality; lack of evidence in favour of one setting or the other; lack of evidence-based guidelines for the frequency and duration of surveillance; disproportionate emphasis placed on the first few years post-treatment, probably dictated by surgical and oncological priorities; a variety of screening policies, as these women are permanently or temporarily or partially excluded from many - but not all - organised screening programmes worldwide; an even greater disparity in follow-up protocols used in the clinical setting; a paucity of data on compliance to mammographic surveillance in both settings; and a difficulty in coordinating the roles of health care providers. In the future, the use of mammography in breast cancer survivors will be influenced by the inclusion of women aged > 69 years in organised screening programmes and the implementation of multidisciplinary breast units, and will probably be investigated by research activities on individual risk assessment and risk-tailored screening. In the interim, current problems can be partially alleviated with some technical solutions in screening data recording, patient flows, and care coordination.
Summary
Mammographic surveillance of breast cancer survivors is situated at the crossroads of numerous different specialist areas of breast cancer control and management. The solutions for current problems probably lie in some important modifications in the conventional screening procedure that are underway or under study. These developments appear to be directed towards a partial modification of the screening rationale, with an adaptation to meet the diversified breast care needs of women. The complexity of the matter constitutes a call to action for several entities to eliminate the barriers to effective research in this field.
doi:10.1186/1472-6963-11-249
PMCID: PMC3203044  PMID: 21970334
22.  Breast and cervical cancer screening among low-income women: impact of a simple centralized HMO intervention. 
In 1994, it was estimated that about 44,500 American women would die from breast cancer and 7000 women from cervical cancer. While early detection methods (screening mammography, breast examinations, and pap smears) have proven to be effective means of decreasing these cancers, they are underused by all groups. In particular, low-income women use them least, resulting in their lower survival and higher mortality rates than the rest of the population. This article quantifies the effect of a simple intervention undertaken by a health maintenance organization (HMO) serving the indigent to improve breast and cervical cancer screening rates. The HMO mailed personal letters and newsletter articles to women members > or = 40 years about the need for cancer prevention. Articles also were printed in the monthly HMO newsletters to providers about the benefits of using these early detection methods. A review of provider claims from 574 women showed that baseline utilization rates for screening mammograms and pap smears before the intervention in year 1 (1990) were 14% and 16.4%, respectively. After the intervention, in years 2 and 3, mammograms had increased to 41% and pap smears to 38% for both years, indicating a levelling off effect of the intervention by year 3. These data show that while a significant improvement in screening behaviors was achieved, the intervention impact was limited to only about one third of the sample on the long term. Further, data do not indicate whether behavioral change was initiated as the member or provider level. More research is needed to increase overall screening behavior among the indigent and their physicians. The results reported here provide a baseline against which more intensive interventions can be measured in this setting.
PMCID: PMC2608093  PMID: 8691500
23.  LONGITUDINAL PREDICTORS OF NON-ADHERENCE TO MAINTENANCE OF MAMMOGRAPHY 
Background
Regular adherence to screening mammography, also known as maintenance of mammography, reduces breast cancer morbidity and mortality. However, mammography maintenance is uncommon, and little is know about why women do not maintain regular screening schedules. We investigated longitudinal predictors of women not maintaining adherence.
Methods
Participants were insured women enrolled in an intervention trial who had screening mammograms eight to nine months prior to study enrollment (n=1,493). Data were collected from 2003 to 2008. We used discrete event history analysis to model non-adherence to mammography maintenance over three successive annual screening intervals (+ 2 months).
Results
Most (54%) women did not maintain screening adherence over three years. Women who did not maintain adherence were more likely to be aged 40 to 49, rate their health fair or poor, be less satisfied with their last mammography experiences, report one or more barriers to getting mammograms, be less than completely confident about getting their next mammograms (lower self-efficacy), or have weaker behavioral intentions. The odds of not maintaining adherence decreased over time.
Discussion
While great strides have been achieved in increasing the proportion of women who have received mammograms, most women still are not maintaining regular mammography use over time. Our findings provide insights into targets for future mammography maintenance interventions.
doi:10.1158/1055-9965.EPI-09-1120
PMCID: PMC2852896  PMID: 20354125
Mammography; breast cancer; maintenance; guideline adherence; health behavior
24.  Breast density as indicator for the use of mammography or MRI to screen women with familial risk for breast cancer (FaMRIsc): a multicentre randomized controlled trial 
BMC Cancer  2012;12:440.
Background
To reduce mortality, women with a family history of breast cancer often start mammography screening at a younger age than the general population. Breast density is high in over 50% of women younger than 50 years. With high breast density, breast cancer incidence increases, but sensitivity of mammography decreases. Therefore, mammography might not be the optimal method for breast cancer screening in young women. Adding MRI increases sensitivity, but also the risk of false-positive results. The limitation of all previous MRI screening studies is that they do not contain a comparison group; all participants received both MRI and mammography. Therefore, we cannot empirically assess in which stage tumours would have been detected by either test.
The aim of the Familial MRI Screening Study (FaMRIsc) is to compare the efficacy of MRI screening to mammography for women with a familial risk. Furthermore, we will assess the influence of breast density.
Methods/Design
This Dutch multicentre, randomized controlled trial, with balanced randomisation (1:1) has a parallel grouped design. Women with a cumulative lifetime risk for breast cancer due to their family history of ≥20%, aged 30–55 years are eligible. Identified BRCA1/2 mutation carriers or women with 50% risk of carrying a mutation are excluded. Group 1 receives yearly mammography and clinical breast examination (n = 1000), and group 2 yearly MRI and clinical breast examination, and mammography biennially (n = 1000).
Primary endpoints are the number and stage of the detected breast cancers in each arm. Secondary endpoints are the number of false-positive results in both screening arms. Furthermore, sensitivity and positive predictive value of both screening strategies will be assessed. Cost-effectiveness of both strategies will be assessed. Analyses will also be performed with mammographic density as stratification factor.
Discussion
Personalized breast cancer screening might optimize mortality reduction with less over diagnosis. Breast density may be a key discriminator for selecting the optimal screening strategy for women < 55 years with familial breast cancer risk; mammography or MRI. These issues are addressed in the FaMRIsc study including high risk women due to a familial predisposition.
Trial registration
Netherland Trial Register NTR2789
doi:10.1186/1471-2407-12-440
PMCID: PMC3488502  PMID: 23031619
Breast cancer; Familial risk; Screening; MRI; Breast density; Cost-effectiveness
25.  False-positive results in the randomised controlled trial of mammographic screening from age 40 (‘Age’ trial) 
Background
False-positive recall is a recognised disadvantage of mammographic breast screening and the rate of such recalls may be higher in younger women, potentially limiting the value of screening below age 50.
Methods
Attendance and screening outcome data for 53 884 women in the intervention arm of the UK Age trial were analysed to report observed false-positive recall rates during 13 years of trial fieldwork. The Age trial was a randomised controlled trial of the effect of mammographic screening from age 40 on breast cancer mortality, conducted in 23 NHS Screening centres between 1991 and 2004. Women randomised to the intervention arm were offered annual invitation to mammography from age 40/41 to age 48.
Results
Overall, 7893 women (14.6% of women the intervention arm and 18.1% of women attending at least one routine screen) experienced one or more false-positive screen during the trial. The rates of false-positive mammography at first and subsequent routine screens were 4.9% and 3.2%, respectively. The cumulative false-positive rate over seven screens was 20.5%. Eighty-nine percent of women who had a false-positive recall at their previous screen attended their next invitation to routine screening.
Conclusions
Rates of false-positive recall in the Age trial were comparable with the national screening programme, however, the positive predictive value of referral was lower. Experiencing a false-positive screen did not appear to lessen the likelihood of re-attendance in the trial.
Impact
The question of greatly increased false-positive rates in this age group and of their compromising re-attendance is refuted by the findings of this study.
doi:10.1158/1055-9965.EPI-10-0623
PMCID: PMC2978129  PMID: 20837718
breast; screening; false-positive; age; trial

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