Cumulative Breast Cancer Mortality Research Articles

Abstract P1-06-04: IMPACTS OF TREATMENT DELAY ON BREAST CANCER MORTALITY AND BENEFIT OF TIMELY CARE IN BLACK AND NON-BLACK WOMEN

Abstract BACKGROUND: The impact of treatment delays on cancer outcomes has been well documented, but few published studies explicitly attempt to identify subgroups which would benefit the most from potential interventions improving timeliness of care. Using the state of North Carolina and breast cancer as an example, we sought to quantify race-specific associations between frontline treatment delay and breast cancer mortality, and estimate the potential impact of improvements in timeliness by racial sub-group. METHODS: We conducted a retrospective cohort study, utilizing multipayer insurance claims linked to cancer registry data from the Cancer Information and Population Health Resource, of females diagnosed with stage I-III breast cancer from 2004 to 2014. Our exposure of interest was treatment delay, defined as initial cancer directed therapy received ≥ 60 days after diagnosis. Our outcome was death certificate identified breast cancer mortality within 5-years of follow-up. To quantify the association between treatment delay and mortality we estimated hazard ratios (HR) and 95% confidence limits (CL) where non-breast cancer deaths were treated as competing events. We then simulated the effect of treating all patients within 60 days using inverse probability of treatment weighting (IPTW), and estimated the potential impact by comparing the simulated data with observed data. Models were adjusted for age and stage at diagnosis, tumor grade, hormone receptor status, and modality of first treatment. Models were stratified by race, dichotomized as Black or non-Black, and geographic subregion for evaluation. RESULTS: Our analytic cohort comprised 21,200 patients, of whom 19% were Black. Treatment delays >60 days were twice as frequent among Black compared with non-Black patients (13.5% vs. 6.5%). We found a positive association between treatment delay and breast cancer mortality in the overall cohort (HR=1.3; CL: 1.1, 1.6). The association differed between Black (HR=1.4; CL: 1.1, 1.8) and Non-Black (HR=1.2; CL: 0.9, 1.6) patient subgroups. For both racial groups, the strength of the relationship between treatment delay and mortality varied across geographic subregions. The estimated potential improvement in 5-year cumulative breast cancer mortality from delivering timely care to all patients differed in magnitude across sub-populations. The magnitude of potential improvement in breast cancer mortality at 5 years in the overall analytic cohort was 0.3% (5-year risk of breast cancer mortality in observed cohort: 7.2% vs 6.9% with simulated universal timely treatment). In the Black subcohort, the potential decrease in mortality for timely treatment was 1.0% (observed: 12.3% vs simulated: 11.4%), while in the non-Black population the potential decrease was 0.1% (observed: 6.1% vs simulated: 5.9%). CONCLUSIONS: The magnitude of association between delayed treatment of stage I-III breast cancer and breast cancer mortality differed between Black and non-Black patients, highlighting that interventions to avert treatment delays may have a meaningful impact for this group. Further research is needed to identify factors underlying this difference, which may include a direct effect of differences in timeliness, or downstream differences in the intensity and quality of cancer care beyond the 60-day landmark for delayed patients. Our findings suggest that comprehensive intervention at the state level to improve the timeliness of breast cancer treatment could potentially reduce breast cancer mortality, and that targeting such intervention to patient groups with larger projected benefit, such as Black patients, may be a more efficient use of resources. We have illustrated how a counterfactual approach may be useful in identifying subgroups where focused intervention efforts may yield greater improvements in outcomes. Citation Format: Bradford Jackson, Stephanie Wheeler, Juan Yanguela, Matthew LeBlanc, Tzy-Mey Kuo, Christopher Baggett, Katherine Reeder-Hayes. IMPACTS OF TREATMENT DELAY ON BREAST CANCER MORTALITY AND BENEFIT OF TIMELY CARE IN BLACK AND NON-BLACK WOMEN [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P1-06-04.

Effectiveness of Mammography Screening on Breast Cancer Mortality - A Study Protocol for Emulation of Target Trials Using German Health Claims Data.

The efficacy of mammography screening in reducing breast cancer mortality has been demonstrated in randomized trials. However, treatment options - and hence prognosis - for advanced tumor stages as well as mammography techniques have considerably improved since completion of these trials. Consequently, the effectiveness of mammography screening under current conditions is unclear and controversial. The German mammography screening program (MSP), an organized population-based screening program, was gradually introduced between 2005 and 2008 and achieved nation-wide coverage in 2009. We describe in detail a study protocol for investigating the effectiveness of the German MSP in reducing breast cancer mortality in women aged 50 to 69 years based on health claims data. Specifically, the proposed study aims at estimating per-protocol effects of several screening strategies on cumulative breast cancer mortality. The first analysis will be conducted once 10-year follow-up data are available. We will use claims data from five statutory health insurance providers in Germany, covering approximately 37.6 million individuals. To estimate the effectiveness of the MSP, hypothetical target trials will be emulated across time, an approach that has been demonstrated to minimize design-related biases. Specifically, the primary contrast will be in terms of the cumulative breast cancer mortality comparing the screening strategies of "never screen" versus "regular screening as intended by the MSP". In Germany, the utilization of data from health insurances for scientific research is regulated by the Code of Social Law. All involved health insurance providers as well as the responsible authorities approved the use of the health claims data for this study. The Ethics Committee of the University of Bremen determined that studies based on claims data are exempt from institutional review. The findings of the proposed study will be published in peer-reviewed journals.

Mortality After Late Breast Cancer Recurrence in Denmark.

Late breast cancer (BC) recurrence (ie, ≥ 10 years after primary diagnosis) may have a more favorable prognosis than earlier recurrence. We investigated the risk of BC death after late recurrence, identified prognostic factors, and compared survival after early and late recurrence. Using the Danish Breast Cancer Group and other nationwide databases, we identified women with early or late BC recurrence during 2004-2018, who were alive 6 months after recurrence. We followed them until BC death, death from other causes, emigration, 10 years, or December 31, 2018, whichever came first. We calculated mortality rates (MRs) per 1,000 person-years (PY) and cumulative BC mortality, for early versus late recurrence, and by characteristics of the primary tumor and the late recurrence. Using Cox regression, we calculated adjusted hazard ratios (HRs) for BC death, accounting for death from other causes as competing risks. Among 2,004 patients with late recurrence, 721 died of BC with a median survival time of 10 years (MR = 84.8 per 1,000 PY; 10-year cumulative mortality = 50%). Among 1,528 patients with early recurrence, 1,092 BC deaths occurred with a median survival time of 4 years (MR = 173.9 per 1,000 PY; 10-year cumulative mortality = 72%). We observed a lower hazard of BC-specific death among patients who developed late compared with early recurrence (hazard ratio = 0.72; 95% CI, 0.62 to 0.85). Advanced stage at primary diagnosis, distant metastases, adjuvant treatment for locoregional recurrence, and systemic treatment for distant recurrence were associated with increased mortality after late recurrence. Breast-conserving surgery at primary diagnosis, locoregional recurrence, and surgery for recurrence were associated with lower mortality after late recurrence. Patients with late recurrence had more favorable prognosis than patients with early recurrence. The localization of recurrent disease was the main prognostic factor for BC death.

Abstract P3-12-18: Mortality after late breast cancer recurrence in Denmark

Abstract Purpose: Late recurrence (i.e., ≥10 years after primary diagnosis) may have a more favorable prognosis than earlier recurrence. We investigated the risk of breast cancer (BC) death after late recurrence and identified prognostic factors. Furthermore, we compared survival between late and early recurrence. Methods: Using the Danish Breast Cancer Group and other nationwide databases, we identified women with early or late BC recurrence during 2004-2018, who were alive 6 months after recurrence. We followed them until BC death, death from other causes, emigration, ten years or 31/12/2018. We calculated mortality rates (MRs) per 1000 person-years (PY) and cumulative BC mortality, for early versus late recurrence and by characteristics of the primary tumor and of the late recurrence. Using Cox regression, we calculated adjusted hazard ratios (HRs) for BC death, accounting for death from other causes as competing risk. Results: Among 2,004 patients with late recurrence, 721 died of BC with a median survival time of 3 years (MR= 84.8 per 1000 PY; 10-year cumulative mortality=50%). Among 1,573 patients with early recurrence, 1,092 BC deaths occurred with a median survival time of 2.6 years (MR= 173.9 per 1000 PY; 10-year cumulative mortality=72%). Advanced stage at primary diagnosis, distant metastases, and adjuvant recurrence treatments were associated with increased mortality, while breast-conserving surgery at primary diagnosis, loco-regional recurrence, and recurrence surgery were associated with lower mortality. Conclusion: Patients with late recurrence had a more favorable prognosis than patients with early recurrence. The localization of recurrent disease was the main prognostic factor for BC death. Citation Format: Rikke Noergaard Pedersen, Lene Mellemkjær, Bent Ejlertsen, Mette Nørgaard, Deirdre Cronin-Fenton. Mortality after late breast cancer recurrence in Denmark [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-12-18.

Mortality after contralateral breast cancer in Denmark.

How a second breast cancer diagnosis affects survival in comparison with unilateral breast cancer (UBC) is unclear. Prognostic factors for contralateral breast cancer (CBC) are also not well established. We aimed to investigate the survival pattern after CBC with particular focus on time between first and second breast cancer diagnosis and age at CBC diagnosis. Within the nationwide Danish Breast Cancer Cooperative Group database, we identified 68,466 breast cancer patients diagnosed during 1978-2012. Patients who subsequently developed CBC were identified in a previously established database (N = 3004). Patients were followed for breast cancer-specific death in the Danish Register of Causes of Death until 2015. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox proportional hazard regression models. Cumulative breast cancer mortality from date of CBC was estimated using the Aalen-Johansen method. Compared with UBC patients, the rate of dying from breast cancer was more than twofold higher following a CBC diagnosis, after adjustment for age, period, tumor characteristics, and treatment of the first breast cancer (HR 2.48; 95% CI 2.31-2.66). Short time interval (< 5years) was associated with higher breast cancer-specific mortality after CBC among patients < 70years at CBC diagnosis compared with longer time intervals, but not among patients ≥ 70years at CBC diagnosis. Breast cancer-specific mortality rates were markedly higher after compared with before a CBC diagnosis. We found higher breast cancer-specific mortality after CBC associated with a short interval between diagnoses among patients diagnosed with CBC before age 70years.

Cause-specific Mortality in a Population-based Cohort of 9799 Women Treated for Ductal Carcinoma In Situ.

To assess cause-specific mortality in women treated for ductal carcinoma in situ (DCIS). From screening and treatment perspective, it is relevant to weigh the low breast cancer mortality after DCIS against mortality from other causes and expected mortality in the general population. We conducted a population-based cohort study comprising 9799 Dutch women treated for primary DCIS between 1989 and 2004 and estimated standardized mortality ratios (SMRs). After a median follow up of 9.8 years, 1429 patients had died of whom 284 caused by breast cancer (2.9% of total cohort). DCIS patients <50 years experienced higher mortality compared with women in the general population (SMR 1.7; 95% confidence interval, CI: 1.4-2.0), whereas patients >50 had significantly lower mortality (SMR 0.9; 95% CI: 0.8-0.9). Overall, the risk of dying from general diseases and cancer other than breast cancer was lower than in the general population, whereas breast cancer mortality was increased. The SMR for breast cancer decreased from 7.5 (95% CI: 5.9-9.3) to 2.8 (95% CI: 2.4-3.2) for women aged <50 and >50 years, respectively. The cumulative breast cancer mortality 10 years after DCIS was 2.3% for women <50 years and 1.4% for women >50 years treated for DCIS between 1999 and 2004. DCIS patients >50 years had lower risk of dying from all causes combined compared with the general female population, which may reflect differences in health behavior. Women with DCIS had higher risk of dying from breast cancer than the general population, but absolute 10-year risks were low.

St Gallen molecular subtypes in screening-detected and symptomatic breast cancer in a prospective cohort with long-term follow-up.

BackgroundDiagnosis by screening mammography is considered an independent positive prognostic factor, although the data are not fully in agreement. The aim of the study was to explore whether the mode of detection (screening‐detected versus symptomatic) adds prognostic information to the St Gallen molecular subtypes of primary breast cancer, in terms of 10‐year cumulative breast cancer mortality (BCM).MethodsA prospective cohort of patients with primary breast cancer, who had regularly been invited to screening mammography, were included. Tissue microarrays were constructed from primary tumours and lymph node metastases, and evaluated by two independent pathologists. Primary tumours and lymph node metastases were classified into St Gallen molecular subtypes. Cause of death was retrieved from the Central Statistics Office.ResultsA total of 434 patients with primary breast cancer were included in the study. Some 370 primary tumours and 111 lymph node metastases were classified into St Gallen molecular subtypes. The luminal A‐like subtype was more common among the screening‐detected primary tumours (P = 0·035) and corresponding lymph node metastases (P = 0·114) than among symptomatic cancers. Patients with screening‐detected tumours had a lower BCM (P = 0·017), and for those diagnosed with luminal A‐like tumours the 10‐year cumulative BCM was 3 per cent. For patients with luminal A‐like lymph node metastases, there was no BCM. In a stepwise multivariable analysis, the prognostic information yielded by screening detection was hampered by stage and tumour biology.ConclusionThe prognosis was excellent for patients within the screening programme who were diagnosed with a luminal A‐like primary tumour and/or lymph node metastases. Stage, molecular pathology and mode of detection help to define patients at low risk of death from breast cancer.

The Effect of Treatment Advances on the Mortality Results of Breast Cancer Screening Trials: A Microsimulation Model.

Mammography trials, which are the primary sources of evidence for screening benefit, were conducted decades ago. Whether advances in systemic therapies have rendered previously observed benefits of screening less significant is unknown. To compare the outcomes of breast cancer screening trials had they been conducted using contemporary systemic treatments with outcomes of trials conducted with previously used treatments. Computer simulation model of 3 virtual screening trials with similar reductions in advanced-stage cancer cases but reflecting treatment patterns in 1975 (prechemotherapy era), 1999, or 2015 (treatment according to receptor status). Meta-analyses of screening and treatment trials; study of dissemination of primary systemic treatments; SEER (Surveillance, Epidemiology, and End Results) registry. U.S. women aged 50 to 74 years. 10 and 25 years. Population. Mammography, chemotherapy, tamoxifen, aromatase inhibitors, and trastuzumab. Breast cancer mortality rate ratio (MRR) and absolute risk reduction (ARR) obtained by the difference in cumulative breast cancer mortality between control and screening groups. At 10 years, screening in a 1975 trial yielded an MRR of 90% and an ARR of 5 deaths per 10,000 women. A 2015 screening trial yielded a 10-year MRR of 90% and an ARR of 3 deaths per 10,000 women. Greater reductions in advanced-stage disease yielded a greater screening effect, but MRRs remained similar across trials. However, ARRs were consistently lower under contemporary treatments. When contemporary treatments were available only for early-stage cases, the MRR was 88%. Disease models simplify reality and cannot capture all breast cancer subtypes. Advances in systemic therapies for breast cancer have not substantively reduced the relative benefits of screening but have likely reduced the absolute benefits because of their positive effect on breast cancer survival. University of Washington and National Cancer Institute.

Abstract P1-12-17: Mature data (&amp;gt; 25 years) on 2 years adjuvant tamoxifen treatment in premenopausal women with breast cancer: Time to re-emphasize the progesterone receptor as predictive factor?

Abstract Background In 2011 The Early Breast Cancer Trialists' Collaborative Group (EBCTCG) reported that five years of adjuvant tamoxifen (TAM) significantly reduces the 15-year risks of breast cancer recurrence and death. Moreover, the estrogen receptor (ER) was considered the clinically most relevant predictive factor for efficacy of TAM treatment. In premenopausal patients participating in a randomized trial of 2 years of adjuvant TAM, we have previously reported on increased recurrence free survival in patients with ER- and PR-positive disease and a trend for increased overall survival in patients with PR-positive tumors. The median follow-up time was 13.9 years for patients without events. Since the effect on mortality may increase beyond year 10, we investigated more mature of data. Aims To investigate the long-term effect of 2 years adjuvant TAM in premenopausal patients choosing cumulative mortality (CM) and cumulative breast cancer mortality (CBCM) as end-points. Methods Premenopausal patients (n=564) with stage II breast cancer were included in a Swedish randomized multicenter trial between 1986-1991 and allocated to 2 years of TAM (n=276) or no treatment (n=288). The hormone receptor status of the tumor was known for 541 (96%) of the patients included, determined by immunohistochemistry or cytosol-based methods. Less than 2% were treated with adjuvant chemotherapy and they were equally distributed between the two groups. Median follow-up time was 26.3 years (22.7-29.7). Mortality data was obtained from the Swedish Cause of Death Register. Results Death from any cause was recorded among 312 (55%) of the patients, and 265 (47%) of the deaths were due to breast cancer. Two years of TAM decreased CM and CBCM in all patients irrespective of hormonal receptor status (n=564) (CM: HR 0.81; 95% CI: 0.65-1.02, p=0.070; CBCM: HR 0.79; 95% CI: 0.61-1.01, p=0.058), as well as in patients with ER-positive disease (n=346) (CM: HR 0.77; 95% CI: 0.57-1.03, p=0.077; CBCM: HR 0.72; 95% CI: 0.52-1.01, p=0.051), however not strictly significant. Importantly, in patients with PR-positive tumors, TAM significantly reduced CM and CBCM (CM: HR 0.73; 95% CI: 0.55-0.98, p=0.037; CBCM: HR 0.68; 95% CI: 0.49-0.94, p=0.020). Moreover, in patients with ER- and PR positive tumors TAM decreased CM (HR 0.74; 95% CI: 0.55-1.01, p=0.057) and CBCM (HR 0.69; 95% CI: 0-49-0.97, p=0.033), whereas there was no effect of TAM in patients with ER-positive and PR-negative tumors (p=0.97 and p=0.99, respectively). Conclusions The present study demonstrates that 2 years of adjuvant TAM as monotherapy significantly reduced CM and CBCM in premenopausal women with PR-positive tumors as well as CBCM in ER- and PR-positive tumors, after &amp;gt; 25 years of follow-up. Five years of adjuvant TAM have been proven to reduce mortality rates at 15 years, but we herein show that also 2 years of TAM yields a survival benefit at 25 years. In the latest meta-analysis from EBCTCG, PR did not add predictive information in patients with ER-positive tumors, but according to our results the significance of PR, as a predictive factor for TAM efficacy, should be re-emphasized in premenopausal women. Citation Format: Maria Ekholm, Pär-Ola Bendahl, Mårten Fernö, Bo Nordenskjöld, Olle Stål, Lisa Rydén. Mature data (&amp;gt; 25 years) on 2 years adjuvant tamoxifen treatment in premenopausal women with breast cancer: Time to re-emphasize the progesterone receptor as predictive factor? [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P1-12-17.

What is the point: will screening mammography save my life?

BackgroundWe 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.MethodsTo 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.ResultsBecause 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.ConclusionThe 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.

Long-term effects of mammography screening: updated overview of the Swedish randomised trials

There has been much debate about the value of screening mammography. Here we update the overview of the Swedish randomised controlled trials on mammography screening up to and including 1996. The Kopparberg part of the Two-County trial was not available for the overview, but the continuation of the Malmö trial (MMST II) has been added. The article also contains basic data from the trials that have not been presented before. Methods The trials (n=247010, invited group 129750, control group 117260) have been followed up by record linkage to the Swedish Cancer and Cause of Death Registers. The relative risks (RR) for breast cancer death and mortality were calculated for the invited and the control groups. The trial-specific as well as the age-specific effects were analysed. RRs were calculated by the density method, with total person-time experience of the cohort by time interval of follow-up as a basis for estimating mortality rates. We calculated weighted RRs and 95% CI with the Mantel-Haenszel procedure. The median trial time-the time from randomisation until the first round was completed for the control group or if the control group was not invited, until end of follow-up-was 6.5 years (range 3.0-18.1). The median follow-up time, the time from randomisation, to the end of follow-up, was 15.8 years (5.8-20.2). There were 511 breast cancer deaths in 1864770 women-years in the invited groups and 584 breast cancer deaths in 1688440 women-years in the control groups, a significant 21% reduction in breast cancer mortality (RR=0.79, 95% CI 0.70-0.89). The reduction was greatest in the age group 60-69 years at entry (33%). Looking at 5-year age groups, there were statistically significant effects in the age groups 55-59, 60-64, and 65-69 years (RR=0.76, 0.68, and 0.69, respectively). There was a small effect in women 50-54 years at randomisation (RR=0.95). The benefit in terms of cumulative breast cancer mortality started to emerge at about 4 years after randomisation and continued to increase to about 10 years. Thereafter the benefit in absolute terms was maintained throughout the period of observation. The age-adjusted relative risk for the total mortality was 0.98 (0.96-1.00). The advantageous effect of breast screening on breast cancer mortality persists after long-term follow-up. The recent criticism against the Swedish randomised controlled trials is misleading and scientifically unfounded.

The Attack on Breast Cancer Screening

The Attack on Breast Cancer Screening

Breast cancer screening with mammography: overview of Swedish randomised trials

Despite encouraging results from screening trials the efficacy of mammography in reducing mortality remains somewhat controversial. Five studies have been done in Sweden. This overview, based on 282 777 women followed for 5-13 years in randomised trials in Malmö, Kopparberg, Östergötland, Stockholm, and Gothenburg, reveals a 24% (95% confidence interval 13-34%) significant reduction of breast cancer mortality among those invited to mammography screening compared with those not invited. To avoid the potential risk of differential misclassification causes of death were assessed by an independent end-point committee after a blinded review of all fatal breast cancer cases. The mortality reduction was similar, irrespective of the end-point used for evaluation ("breast cancer as underlying cause of death" or "breast cancer present at death"). There was a consistent risk reduction associated with screening in all studies, although the point estimate of the relative risk for all ages varied non-significantly between 0·68 and 0·84. The cumulative breast cancer mortality by time since randomisation was estimated at 1·3 per 1000 within 6 years in the invited group compared with 1·6 in the control group. The corresponding figures after 9 years are 2·6 and 3·3 and after 12 years 3·9 and 5·1. The largest reduction of breast cancer mortality (29%) was observed among women aged 50-69 at randomisation. Among women 40-49 there was a non-significant 13% reduction. In this younger age group cumulative breast cancer mortality was similar in the invited and control group during the first 8 years of follow-up. After 8 years there was a difference in favour of the invited women. There was no evidence of any detrimental effect of screening in terms of breast cancer mortality in any age group. Among women aged 70-74 years screening seems to have had only a marginal impact.

Study of the role of breast self-examination in the reduction of mortality from breast cancer

The protocol of a study, sponsored by the World Health Organization, of the role of breast self-examination (BSE) in reduction of mortality from breast cancer is presented. The major objective of the study is to determine the effect of a BSE programme on mortality from breast cancer. A population of over 193 000 women aged 40 to 64 has been defined in Moscow and St Petersburg and randomised to study and control groups. In Moscow the education programme is based on a two-way communication principle allowing efficient person-to-person education in groups of up to 20 individuals and feedback information through specially designed personal calendars. In St Petersburg, class and individual instruction is carried out. After a 1-year feasibility study the project is planned to last for 15 years. It consists of an aggressive education programme, during and following which, all newly diagnosed breast cancers will be registered and treated, and followed up for 3 to 15 years. A key issue of the study is compliance of the population with BSE. The frequency and competence of BSE practice has been defined in subsamples of 400 randomly selected women by means of surveys at 6 months, 1, 2 and 3 years after the start of the project. The study is expected to result in the accrual of more than 1470 new breast cancer cases and 778 deaths from breast cancer. The power of the study is expected to permit detection of a 30% reduction in cumulative breast cancer mortality, assuming that 50–70% of the women in the study group practise BSE.