A case-control study to evaluate the impact of the breast screening programme on mortality in England.

BACKGROUND: Over the past 30 years since the implementation of the National Health Service Breast Screening Programme, improvements in diagnostic techniques and treatments have led to the need for an up-to-date evaluation of its benefit on risk of death from breast cancer. An initial pilot case-control study in London indicated that attending mammography screening led to a mortality reduction of 39%. METHODS: Based on the same study protocol, an England-wide study was set up. Women aged 47-89 years who died of primary breast cancer in 2010 or 2011 were selected as cases (8288 cases). When possible, two controls were selected per case (15,202 controls) and were matched by date of birth and screening area. RESULTS: Conditional logistic regressions showed a 38% reduction in breast cancer mortality after correcting for self-selection bias (OR 0.62, 95% CI 0.56-0.69) for women being screened at least once. Secondary analyses by age group, and time between last screen and breast cancer diagnosis were also performed. CONCLUSIONS: According to this England-wide case-control study, mammography screening still plays an important role in lowering the risk of dying from breast cancer. Women aged 65 or over see a stronger and longer lasting benefit of screening compared to younger women.

Effect of mammographic screening from age 40 years on breast cancer mortality (UK Age trial): final results of a randomised, controlled trial.

BACKGROUND: The appropriate age range for breast cancer screening remains a matter of debate. We aimed to estimate the effect of mammographic screening at ages 40-48 years on breast cancer mortality. METHODS: We did a randomised, controlled trial involving 23 breast screening units across Great Britain. We randomly assigned women aged 39-41 years, using individual randomisation, stratified by general practice, in a 1:2 ratio, to yearly mammographic screening from the year of inclusion in the trial up to and including the calendar year that they reached age 48 years (intervention group), or to standard care of no screening until the invitation to their first National Health Service Breast Screening Programme (NHSBSP) screen at approximately age 50 years (control group). Women in the intervention group were recruited by postal invitation. Women in the control group were unaware of the study. The primary endpoint was mortality from breast cancers (with breast cancer coded as the underlying cause of death) diagnosed during the intervention period, before the participant's first NHSBSP screen. To study the timing of the mortality effect, we analysed the results in different follow-up periods. Women were included in the primary comparison regardless of compliance with randomisation status (intention-to-treat analysis). This Article reports on long-term follow-up analysis. The trial is registered with the ISRCTN registry, ISRCTN24647151. FINDINGS: 160 921 women were recruited between Oct 14, 1990, and Sept 24, 1997. 53 883 women (33·5%) were randomly assigned to the intervention group and 106 953 (66·5%) to the control group. Between randomisation and Feb 28, 2017, women were followed up for a median of 22·8 years (IQR 21·8-24·0). We observed a significant reduction in breast cancer mortality at 10 years of follow-up, with 83 breast cancer deaths in the intervention group versus 219 in the control group (relative rate [RR] 0·75 [95% CI 0·58-0·97]; p=0·029). No significant reduction was observed thereafter, with 126 deaths versus 255 deaths occurring after more than 10 years of follow-up (RR 0·98 [0·79-1·22]; p=0·86). INTERPRETATION: Yearly mammography before age 50 years, commencing at age 40 or 41 years, was associated with a relative reduction in breast cancer mortality, which was attenuated after 10 years, although the absolute reduction remained constant. Reducing the lower age limit for screening from 50 to 40 years could potentially reduce breast cancer mortality. FUNDING: National Institute for Health Research Health Technology Assessment programme.

Addition of ultrasound to mammography in the case of dense breast tissue: systematic review and meta-analysis.

BACKGROUND: Mammography is less effective in detecting cancer in dense than in fatty breasts. METHODS: We undertook a systematic search in PubMed to identify studies on women with dense breasts who underwent screening with mammography supplemented with ultrasound. A meta-analysis was undertaken on the proportion of cancers detected only by ultrasound, out of all screen-detected cancers, and the proportion of women with negative mammography who were referred for assessment following ultrasound screening. RESULTS: Twenty-nine studies satisfied our inclusion criteria. The proportion of total cancers detected only by ultrasound was 0.29 (95% CI: 0.27-0.31), consistent with an approximately 40% increase in the detection of cancers compared to mammography. In the studied populations, this translated into an additional 3.8 (95% CI: 3.4-4.2) screen-detected cases per 1000 mammography-negative women. About 13% (32/248) of cancers were in situ from 17 studies with information on this subgroup. Ultrasound approximately doubled the referral for assessment in three studies with these data. CONCLUSIONS: Studies have consistently shown an increased detection of breast cancer by supplementary ultrasound screening. An inclusion of supplementary ultrasound into routine screening will need to consider the availability of ultrasound and diagnostic assessment capacities.

Screen detection of ductal carcinoma in situ and subsequent incidence of invasive interval breast cancers: a retrospective population-based study.

BACKGROUND: The value of screen detection and treatment of ductal carcinoma in situ (DCIS) is a matter of controversy. At present, the extent to which the diagnosis and treatment of DCIS could prevent the occurrence of invasive breast cancer in the future is not clear. We sought to estimate the association between detection of DCIS at screening and invasive interval cancers subsequent to the relevant screen. METHODS: We obtained aggregate data for screen-detected cancers from 84 local screening units within 11 regional Quality Assurance Reference Centres in England, Wales, and Northern Ireland from the National Health Service Breast Screening Programme. Data for DCIS diagnoses were obtained for women aged 50-64 years who were invited to and attended mammographic breast screening from April 1, 2003, to March 31, 2007 (4 screening years). Patient-level data for interval cancer arising in the 36 months after each of these were analysed by Poisson regression with invasive interval cancer screen detection rate as the outcome variable; DCIS detection frequencies were fitted first as a continuous and then as a categorical variable. We repeated this analysis after adjustment with both small size and high-grade invasive screen-detected cancers. FINDINGS: We analysed data for 5,243,658 women and on interval cancers occurring in the 36 months after the relevant screen. The average frequency of DCIS detected at screening was 1·60 per 1000 women screened (median 1·50 [unit range 0·54-3·56] [corrected to] per 1000 women). There was a significant negative association of screen-detected DCIS cases with the rate of invasive interval cancers (Poisson regression coefficient -0·084 [95% CI -0·13 to -0·03]; p=0·002). 90% of units had a DCIS detection frequency within the range of 1·00 to 2·22 per 1000 women; in these units, for every three screen-detected cases of DCIS, there was one fewer invasive interval cancer in the next 3 years. This association remained after adjustment for numbers of small screen-detected invasive cancers and for numbers of grade 3 invasive screen-detected cancers. INTERPRETATION: The association between screen-detected DCIS and subsequent invasive interval cancers suggests that detection and treatment of DCIS is worthwhile in prevention of future invasive disease. FUNDING: UK Department of Health Policy Research Programme and NHS Cancer Screening Programmes.

An ongoing case-control study to evaluate the NHS Bowel Cancer Screening Programme.

BACKGROUND: Colorectal cancer is the third most common cause of cancer death in both males and females in England. A national bowel cancer screening programme was rolled out in England between 2006 and 2010. In the post-randomised controlled trials epoch, assessment of the impact of the programme using observational studies is needed. This study protocol was set up at the request of the UK Policy Research Unit in Cancer Awareness, Screening and Early Diagnosis to evaluate the effect of the current bowel cancer screening programme on incidence of advanced primary colorectal cancer. METHODS/DESIGN: All incident cases of primary colorectal cancer in England will be included. Cases will be matched to controls with respect to sex, age, area of registration and year of first invitation to screening. Each evaluation round will cover a 2-year period, starting from January 2012, and ongoing thereafter. In the first instance, a pilot will be carried out in a single region. Variables related to colorectal tumour pathology will be obtained to enable selection and matching of cases and controls, and to allow analyses stratification by anatomical subsite within the bowel. Cases at Duke's stage B or worse will be considered as "advanced stage". The influence of sex will also be investigated. The incidence ratio observed in randomised controlled trials between controls (not invited) and non-attender invitees will be used to correct for self-selection bias overall. Screening participation at other national screening programmes (cervical, breast) will also be collected to derive a more contemporaneous adjustment factor for self-selection bias and assess consistency in self-selection correction in female patients.Full ethical approval was obtained from the Health Research Authority. DISCUSSION: The case-control design is potentially prone to a number of biases. The size of the planned study, the design specifications and the development of analytical strategies to cope with bias should enable us to obtain accurate estimates of reduction in incidence of advanced stage disease. The results of analyses by sex and anatomical subsite may highlight the potential need for sex-specific recommendations in the programme.

Opportunistic offering of self-sampling to non-attenders within the English cervical screening programme: a pragmatic, multicentre, implementation feasibility trial with randomly allocated cluster intervention start dates (YouScreen).

Background: Self-sampling has game-changing potential to tackle the declining participation and inequities seen in many organised cervical screening programmes. Wide variation in uptake between settings and mode of kit offer highlight the importance of local piloting. Furthermore, harnessing the benefits of self-sampling in real-world settings has been surprisingly challenging. The YouScreen study estimated the impact of offering self-sampling to non-attenders within the English Programme and evaluated large-scale opportunistic offering of self-sampling in primary care. Methods: A pragmatic modified stepped-wedge implementation feasibility trial with randomly-allocated cluster intervention start dates at primary care practices in England (133 participating, 62 non-participating). Eligible women were aged 25-64 years and ≥6 months overdue for screening ("non-attenders"). Between January 13, 2021 and 30 November, 2021 self-sampling kits were distributed to non-attenders via an opportunistic offer in primary care when they consulted for any reason and direct mailout to those unscreened 15-months after routine invitation. Primary outcomes were the proportion of non-attenders screened each month; change in coverage; and uptake (90 days). YouScreen is registered with ISRCTN:12759467. Findings: 8338 women provided self-samples following recruitment between January 13, 2021 and 30 November, 2021. Self-samples were returned from 65.5% (6061/9248) who accepted an opportunistically offered kit and 12.9% (2777/17,604) directly-mailed kits. Responders were representative of the ethnically diverse and deprived underlying non-attendee population (64% ethnic minority groups, 60% from the two most deprived national quintiles). The self-sampling intervention resulted in a 22% (95% CI 18-26) increase in non-attenders screened per month (per-protocol analysis) and 12% (95% CI 9-15) (intention-to-treat analysis). Change in coverage at participating (mean intervention duration 7.5 months) vs non-participating practices was 1.6% (95% CI 0.4-2.8). Adverse effects were not formally collected. Interpretation: Opportunistically offering self-sampling to under-screened women in primary care could increase coverage in England and potentially reach underserved populations. Funding: North Central London and North East London Cancer Alliance.

Overdiagnosis in breast cancer screening: the importance of length of observation period and lead time.

BACKGROUND: Overdiagnosis in breast cancer screening is a controversial topic. One difficulty in estimation of overdiagnosis is the separation of overdiagnosis from lead time that is the advance in the time of diagnosis of cancers, which confers an artificial increase in incidence when a screening programme is introduced. METHODS: We postulated a female population aged 50-79 with a similar age structure and age-specific breast cancer incidence as in England and Wales before the screening programme. We then imposed a two-yearly screening programme; screening women aged 50-69, to run for twenty years, with exponentially distributed lead time with an average of 40 months in screen-detected cancers. We imposed no effect of the screening on incidence other than lead time. RESULTS: Comparison of age- and time-specific incidence between the screened and unscreened populations showed a major effect of lead time, which could only be adjusted for by follow-up for more than two decades and including ten years after the last screen. From lead time alone, twenty-year observation at ages 50-69 would confer an observed excess incidence of 37%. The excess would only fall below 10% with 25 years or more follow-up. For the excess to be nullified, we would require 30 year follow-up including observation up to 10 years above the upper age limit for screening. CONCLUSION: Studies using shorter observation periods will overestimate overdiagnosis by inclusion of cancers diagnosed early due to lead time among the nominally overdiagnosed tumours.

An ongoing case-control study to evaluate the NHS breast screening programme.

BACKGROUND: In England, a national breast screening programme (NHSBSP) has been in place since 1988, and assessment of its impact on breast cancer incidence and mortality is essential to ensure that the programme is indeed doing more good than harm. This article describes large observation studies designed to estimate the effects of the current programme in terms of the benefits on breast cancer incidence and mortality and detrimental effect in terms of overdiagnosis. The case-control design of the cervical screening programme evaluation was highly effective in informing policy on screening intervals and age ranges. We propose innovative selection of cases and controls and gathering of additional variables to address new outcomes of interest and develop new methodologies to control for potential sources of bias. METHODS/DESIGN: Traditional case-control evaluation of breast screening uses women who have died from breast cancer as cases, and women known to be alive at the time of case death as controls. Breast screening histories prior to the cases' date of first diagnosis are compared. If breast screening is preventing mortality from breast cancer, cases will be characterised by a lesser screening history than controls. All deaths and incident cases of primary breast cancer in England within each 2-year study period will be included in this ongoing evaluation. Cases will be age- and area-matched to controls and variables related to cancer treatment and breast tumour pathology will be obtained to investigate the interplay between screening and treatment, and the effect of screening on incidence of advanced stage disease. Screening attendance at other national screening programmes will also be collected to derive superior adjustment for self-selection bias.The study is registered and has received full ethics approval.

A case-control study to evaluate the impact of the breast screening programme on breast cancer incidence in England.

BACKGROUND: There is uncertainty about overdiagnosis in mammography screening. METHODS: We aimed to estimate the effect of screening on breast cancer incidence and overdiagnosis in the NHS Breast Screening Programme in England. The study included 57,493 cases and 105,653 controls, with cases defined as women diagnosed at ages 47-89 with primary breast cancer, invasive or ductal carcinoma in situ, in 2010 or 2011. Where possible, two controls were selected per case, matched on date of birth and screening area. Conditional logistic regression was used to estimate the effect of screening on breast cancer risk, with adjustment for potential self-selection bias. Results were combined with national incidence data to estimate absolute rates of overdiagnosis. Overdiagnosis was calculated as the cumulative excess of cancers diagnosed in the age group 50-77 in a woman attending three-yearly screening between ages 50 and 70 compared with a woman attending no screens. RESULTS: The estimated number of cases overdiagnosed in women attending all screens in the programme was 679.3 per 100,000 without adjustment for self-selection bias and 261.2 per 100,000 with adjustment. These corresponded to an estimated 9.5% of screen-detected cancers overdiagnosed without adjustment and 3.7% with adjustment for self-selection. CONCLUSIONS: The NHS Breast Screening Programme in England confers at worst modest levels of overdiagnosis.

Benefit of Biennial Fecal Occult Blood Screening on Colorectal Cancer in England: A Population-Based Case-Control Study.

BACKGROUND: The English national bowel cancer screening program offering a guaiac fecal occult blood test began in July 2006. In randomized controlled trials of guaiac fecal occult blood test screening, reductions in mortality were accompanied by reductions in advanced stage colorectal cancer (CRC). We aimed to evaluate the effect of participation in the national bowel cancer screening program on stage-specific CRC incidence as a likely precursor of a mortality effect. METHODS: In this population-based case-control study, cases were individuals diagnosed with CRC aged 60-79 years between January 1, 2012, and December 31, 2013. Two controls per case were matched on geographic region, gender, date of birth, and year of first screening invitation. Screening histories were extracted from the screening database. Conditional logistic regression with correction for self-selection bias was used to estimate odds ratios (odds ratios corrected for self-selection bias [cOR]) and 95% confidence intervals (CIs) by Duke stage, sex, and age. RESULTS: 14 636 individuals with CRC and 29 036 without were eligible for analysis. The odds of CRC (any stage) were increased within 30 days of a screening test and decreased thereafter. No reduction in CRC (any stage) among screened individuals compared with those not screened was observed (cOR = 1.00, 95% CI = 0.89 to 1.15). However, screened individuals had lower odds of Duke stage D CRC (cOR = 0.68, 95% CI = 0.50 to 0.93). We estimate 435 fewer Duke D CRC by age 80 years in 100 000 people screened biennially between ages 60 and 74 years compared with an unscreened cohort. CONCLUSION: The impact of colorectal screening on advanced CRC incidence suggests that the program will meet its aim of reducing mortality.

Saving Mothers' Lives: Reviewing maternal deaths to make motherhood safer: 2006-2008. The Eighth Report of the Confidential Enquiries into Maternal Deaths in the United Kingdom.

In the triennium 2006-2008, 261 women in the UK died directly or indirectly related to pregnancy. The overall maternal mortality rate was 11.39 per 100,000 maternities. Direct deaths decreased from 6.24 per 100,000 maternities in 2003-2005 to 4.67 per 100,000 maternities in 2006­2008 (p = 0.02). This decline is predominantly due to the reduction in deaths from thromboembolism and, to a lesser extent, haemorrhage. For the first time there has been a reduction in the inequalities gap, with a significant decrease in maternal mortality rates among those living in the most deprived areas and those in the lowest socio-economic group. Despite a decline in the overall UK maternal mortality rate, there has been an increase in deaths related to genital tract sepsis, particularly from community acquired Group A streptococcal disease. The mortality rate related to sepsis increased from 0.85 deaths per 100,000 maternities in 2003-2005 to 1.13 deaths in 2006-2008, and sepsis is now the most common cause of Direct maternal death. Cardiac disease is the most common cause of Indirect death; the Indirect maternal mortality rate has not changed significantly since 2003-2005. This Confidential Enquiry identified substandard care in 70% of Direct deaths and 55% of Indirect deaths. Many of the identified avoidable factors remain the same as those identified in previous Enquiries. Recommendations for improving care have been developed and are highlighted in this report. Implementing the Top ten recommendations should be prioritised in order to ensure the overall UK maternal mortality rate continues to decline.

Targeted encouragement of GP consultations for possible cancer symptoms: a randomised controlled trial.

BACKGROUND: For some common cancers, survival is lower in the UK than in comparable high-income countries. AIM: To assess the effectiveness of a targeted postal intervention (to promote awareness of cancer symptoms and earlier help seeking) on patient consultation rates. DESIGN AND SETTING: A two-arm randomised controlled trial was carried out on patients aged 50-84 years registered at 23 general practices in rural and urban areas of Greater London, Greater Manchester, and the North East of England. METHOD: Patients who had not had a consultation at their general practice in the previous 12 months and had at least two other risk factors for late presentation with cancer were randomised to intervention and control arms. The intervention consisted of a posted letter and leaflet. Primary outcome was the number of consultations at the practice with patients randomised to each arm in the 6 months subsequent to posting the intervention. All patients with outcome data were included in the intention-to-treat analyses. RESULTS: In total, 1513 patients were individually randomised to the intervention (n = 783) and control (n = 730) arms between Nov 2016 - May 2017; outcome data were available for 749 and 705 patients, respectively, with a statistically significantly higher rate of consultation in the intervention arm compared with the control arm: 436 versus 335 consultations (relative risk 1.40, 95% confidence interval = 1.11 to 1.77, P = 0.004). There was, however, no difference in the numbers of patients consulting. CONCLUSION: Targeted interventions of this nature can change behaviour; there is a need to develop interventions that can be more effective at engaging patients with primary care. This study demonstrates that targeted interventions promoting both awareness of possible cancer symptoms and earlier health seeking, can change behaviour. There is a need to develop and test interventions that can be more effective at engaging the most at-risk patients.

Concurrent participation in screening for cervical, breast, and bowel cancer in England.

Objectives: To determine how many women participate in all three recommended cancer screening programmes (breast, cervical, and bowel). During their early 60s, English women receive an invitation from all the three programmes. Methods: For 3060 women aged 60­65 included in an England-wide breast screening case­control study, we investigated the number of screening programmes they participated in during the last invitation round. Additionally, using the Fingertips database curated by Public Health England, we explored area-level correlations between participation in the three cancer screening programmes and various population characteristics for all 7014 English general practices with complete data. Results: Of the 3060 women, 1086 (35%) participated in all three programmes, 1142 (37%) in two, 526 (17%) in one, and 306 (10%) in none. Participation in all three did not appear to be a random event (p < 0.001). General practices from areas with less deprivation, with more patients who are carers or have chronic illnesses themselves, and with more patients satisfied with the provided service were significantly more likely to attain high coverage rates in all programmes. Conclusions: Only a minority of English women is concurrently protected through all recommended cancer screening programmes. Future studies should consider why most women participate in some but not all recommended screening.

Annual mammographic screening to reduce breast cancer mortality in women from age 40 years: long-term follow-up of the UK Age RCT.

BACKGROUND: There remains disagreement on the long-term effect of mammographic screening in women aged 40-49 years. OBJECTIVES: The long-term follow-up of a randomised controlled trial that offered annual mammography to women aged 40-49 years. The estimation of the effect of these mammograms on breast cancer and other-cause mortality, and the effect on incidence, with implications for overdiagnosis. DESIGN: An individually randomised controlled trial comparing offering annual mammography with offering usual care in those aged 40-48 years, and thus evaluating the effect of annual screening entirely taking place before the age of 50 years. There was follow-up for an average of 23 years for breast cancer incidence, breast cancer death and death from other causes. We analysed the mortality and incidence data by Poisson regression and estimated overdiagnosis formally using Markov process models. SETTING: Twenty-three screening units in England, Wales and Scotland within the NHS Breast Screening Programme. PARTICIPANTS: Women aged 39-41 years were recruited between 1990 and 1997. After exclusions, a total of 53,883 women were randomised to undergo screening (the intervention group) and 106,953 women were randomised to have usual care (the control group). INTERVENTIONS: The intervention group was invited to an annual breast screen with film mammography, two view at first screen and single view thereafter, up to and including the calendar year of their 48th birthday. The control group received no intervention. Both groups were invited to the National Programme from the age of 50 years, when screening is offered to all women in the UK. MAIN OUTCOME MEASURES: The main outcome measures were mortality from breast cancers diagnosed during the intervention phase of the trial (i.e. before the first National Programme screen at 50 years), mortality from all breast cancers diagnosed after randomisation, all-cause mortality, mortality from causes other than breast cancer, and the incidence of breast cancer. RESULTS: There was a statistically significant 25% reduction in mortality from breast cancers diagnosed during the intervention phase at 10 years' follow-up (relative rate 0.75, 95% confidence interval 0.58 to 0.97; p = 0.03). No reduction was observed thereafter (relative rate 0.98, 95% confidence interval 0.79 to 1.22). Overall, there was a statistically non-significant 12% reduction (relative rate 0.88, 95% confidence interval 0.74 to 1.03; p = 0.1). The absolute benefit remained approximately constant over time, at one death prevented per 1000 women screened. There was no effect of intervention on other-cause mortality (relative rate 1.02, 95% confidence interval 0.97 to 1.07; p = 0.4). The intervention group had a higher incidence of breast cancer than the control group during the intervention phase of the trial, but incidence equalised immediately on the first National Programme screen at the age of 50-52 years. LIMITATIONS: There was 31% average non-compliance with screening and three centres had to cease screening for resource and capacity reasons. CONCLUSIONS: Annual mammographic screening at the age of 40-49 years resulted in a relative reduction in mortality, which was attenuated after 10 years. It is likely that digital mammography with two views at all screens, as practised now, could improve this further. There was no evidence of overdiagnosis in addition to that which already results from the National Programme carried out at later ages. FUTURE WORK: There is a need for research on the effects of modern mammographic protocols and additional imaging in this age group. TRIAL REGISTRATION: Current Controlled Trials ISRCTN24647151. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 55. See the NIHR Journals Library website for further project information. Other funding in the past has been received from the Medical Research Council, Cancer Research UK, the Department of Health and Social Care, the US National Cancer Institute and the American Cancer Society.

It is known that breast cancer screening with mammography (i.e. X-ray of the breasts) in women aged ≥ 50 years leads to a reduction in the number of deaths from breast cancer. In the UK, the NHS Breast Screening Programme offers regular screening to women aged 50­70 years. There is still some disagreement about the effect of such screening on the risk of death from breast cancer for those aged 40­49 years. There is also concern about overdiagnosis, that is, the finding of breast cancer that would not have been diagnosed in a woman's lifetime if she had not been screened. This study recruited 160,921 women aged 39­41 years and randomly assigned one in three of the women to be offered annual mammographic screening from age 40 to 48 years. The women were followed up for occurrence of breast cancer, death from breast cancer and death from all other causes. We found that the women who were offered the screening were 25% less likely to die of breast cancer in the first 10 years in the trial. This mortality reduction was reduced with later follow-up, with a 12% reduction after an average of 23 years. There was no effect of offering screening on death from other causes. During the early years of the trial, the women offered screening had larger numbers of breast cancers diagnosed, but this excess disappeared after the first National Programme screen. This suggests that there is no overdiagnosis from screening those aged 40­49 years over and above that which already results from screening those aged ≥ 50 years.

Explaining the Better Prognosis of Screening-Exposed Breast Cancers: Influence of Tumor Characteristics and Treatment.

BACKGROUND: In England, population mammographic screening has been offered to women for over 20 years. Overall decrease in breast cancer mortality rates and improvements in cancer awareness and organization of medical care over this period call for a more current evaluation of the mediators behind the better prognosis of screening-exposed breast cancers. METHODS: A case-control study was conducted within the English National Breast Screening Program. Women who died from primary breast cancer in 2008 to 2009 were matched (by year of birth, screening invitation, and area) to controls that received a diagnosis of invasive breast cancer at the time of the case diagnosis but survived the case death. Data were analyzed by unconditional logistic regression with adjustment for matching factors. RESULTS: The unadjusted OR for dying from breast cancer associated with ever having attended breast screening was 0.44 [95% confidence interval (CI), 0.33-0.58]. After adjustment for lead time, overdiagnosis, and self-selection, the OR increased to 0.69 (95% CI, 0.50-0.94). Adjusting for tumor size, lymph node status, stage, grade, histopathology, and laterality accounted for all the screening effect (OR, 1.00; 95% CI, 0.71-1.40). Further adjustment for treatment factors only had a minimal impact on the OR (OR, 1.02; 95% CI, 0.72-1.45). CONCLUSIONS: Our results suggest that earlier diagnosis, as reflected by tumor characteristics, remains the major mediator of the improvement in breast cancer survival due to participation in mammographic screening. IMPACT: Mammographic screening continues to prevent breast cancer-related deaths in the epoch of adjuvant systemic therapy.

Impact of Screening on Breast Cancer Mortality: The UK Program 20 Years On.

BACKGROUND: With changes in diagnosis, treatment, and management of breast cancer since the mammography screening trials, there is a need to evaluate contemporary breast screening programs. A case-control study was set up to assess the current impact of attendance in the English Breast Screening Program on breast cancer mortality. METHODS: Cancer registry cases who died from primary breast cancer ages 47 to 89 years in London in 2008 to 2009 (869 women) were matched to 1 or 2 general population controls (1,642 women) with no diagnosis of breast cancer at the time of the case's diagnosis, who were alive at the case's death. Cases and controls were matched for date of birth and screening area, and had been invited to breast screening at least once prior to the case's diagnosis. ORs were estimated using conditional logistic regression. Self-selection bias was addressed using contemporaneous attendance at the cervical screening program. Sensitivity analyses were undertaken to assess the likely effect of lead time bias. RESULTS: Attendance at breast screening resulted in a breast cancer mortality reduction of 39% [OR, 0.61; 95% confidence interval (CI), 0.44-0.85] after self-selection correction. Attendance in the last 3 years prior to diagnosis resulted in a 60% mortality reduction (OR, 0.40; 95% CI, 0.31-0.51). Lead time bias effects were negligible. CONCLUSION: Our results suggest that community breast screening programs provide their expected benefit in terms of reducing the risk of breast cancer death among women participating. IMPACT: Mammography is an important tool for reducing breast cancer mortality and its impact could be increased by encouraging regular attendance.