Mass screening for breast cancer in Japan

To establish effective mass screening projects for breast cancer, our study group (Tominaga group) was co-sponsored by the Ministry of Welfare. From 1968 to 1986, 643,513 women at the initial screening and 719,189 women at the subsequent screening were examined by physical examination. Abnormalities were found in 24,864 (3.9%) and 23,880 (3.3%) of these women, respectively. Cancer was detected in 833 women (detection rate 0.13%) and 428 women (0.06%), respectively. To establish the criteria for assessing the life-prolonging effect of mass screening for breast cancer, clinical stage and prognosis of breast cancer detected by mass screening were compared with those for matched patients in outpatients clinics. Early stages were significantly more common in the patients detected by mass screening. The 5-year survival rate was significantly higher in the patients detected by mass screening (91.7% vs. 85.6%; P less than 0.01), but the difference with the other group was not significant (80.5% vs. 78.1%). Women who had conducted breast self-examination (BSE) showed a higher survival rate than those who had not. We were not able to confirm the general belief that interval cancer is more aggressive in nature and shows a poorer prognosis than the cancer detected through periodic screening.     

Interval cancers in the Norwegian breast cancer screening program: frequency, characteristics and use of HRT.

Breast cancers diagnosed between screening examinations among women who attend a breast cancer screening program are defined as interval cancers. The Norwegian Breast Cancer Screening Program started as a pilot project in 1996, and data from the first 2-year interval are available. Our study quantifies interval cancers in the pilot project and explores characteristics and factors that may be associated with interval cancer. Interval cancers in the screening population were identified through the Cancer Registry of Norway. The frequency of invasive interval cancer was calculated as cases per 10,000 screened and as observed/expected ratio. Characteristics of the interval cancers were compared to screening-detected and clinical cancers. Breast density was assessed in a blinded review of 3 categories of screening mammograms. Information on hormone replacement therapy (HRT) use was collected from a questionnaire. The frequency of invasive interval cancers was 18.2 (15.9-20.7) per 10,000 screened and the observed/expected ratio was 0.49 (0.43-0.56). The frequency in the second year of the interval was higher than reported from other programs. The median tumor size of the interval cancers was 19.5 mm and 44.0% of the patients had affected axillary lymph nodes. The interval cancer cases had higher proportions of dense breasts and reported use of HRT compared to screen normal and screening-detected cases. The reported frequency of interval cancers is similar to comparable programs. The interval cancers differed significantly from the cancers detected in the first screening round and were more similar to clinical cancers. Interval cancer was associated with dense breasts and use of HRT. Screening programs must keep these associations in focus.     

Favourable prognostic factors of subsequent screen-detected breast cancers among women aged 50-69

Most studies reporting more favourable biological features of screen-detected breast cancers compared with symptomatic or interval cancers include initial or prevalent screens and therefore may not indicate the real benefit of screening on breast cancer mortality. We conducted case-case comparisons within a cohort of eligible women (N=771 715) who were aged 50-69 between 1 January 1995 and 31 December 2003. A randomly selected sample of breast cancers (N=1848) diagnosed among these women were compared by detection method. Tumour characteristics of interval cancers (N=362) diagnosed after 6-24 months of a negative screen or symptomatic breast cancers (N=491) were compared with subsequent screen-detected breast cancers diagnosed within 6 months of a positive screen (N=995) using polytomous logistic regression. Tumours were evaluated for clinical presentation, histology and expression of hormone receptors. Women with symptomatic detected [odds ratio (OR)=7.48, 95% confidence interval (CI)=5.38-10.38] and interval cancers (OR=2.20, 95% CI=1.56-3.10) were more often diagnosed at stage III-IV versus I than women with rescreen-detected cancers. After adjusting for tumour size, women with symptomatic cancers had tumours of higher grade (OR=1.50, 95% CI=1.05-2.15) and mitotic score (OR=1.69, 95% CI=1.15-2.49) and women with interval cancers had tumours of higher mitotic score (OR=1.52, 95% CI=1.01-2.28) compared with women diagnosed at screening. Subsequent screen-detected cancers are not only detected at an earlier stage but are also less aggressive, leading to a better prognosis. As long-term mortality reduction for breast screening may depend on subsequent screens, our study indicates that mammography screening can be effective in women aged 50-69.     

Interval cancers in the Dutch breast cancer screening programme.

The nationwide breast cancer screening programme in The Netherlands for women aged 50-69 started in 1989. In our study we assessed the occurrence and stage distribution of interval cancers in women screened during 1990-1993. Records of 0.84 million screened women were linked to the regional cancer registries yielding a follow-up of at least 2.5 years. Age-adjusted incidence rates and relative (proportionate) incidences per tumour size including ductal carcinoma in-situ were calculated for screen-detected and interval cancers, and cancers in not (yet) screened women, comparing them with published data from the UK regions North West and East Anglia. In total 1527 interval cancers were identified: 0.95 and 0.99 per 1000 woman-years of follow-up in the 2-year interval after initial and subsequent screens respectively. In the first year after initial screening interval cancers amounted to 27% (26% after subsequent screens) of underlying incidence, and in the second year to 52% (55%). Generally, interval cancers had a more favourable tumour size distribution than breast cancer in not (yet) screened women. The Dutch programme detected relatively less (favourable) invasive cancers in initial screens than the UK programme, whereas the number of interval cancers confirms UK findings. Measures should be considered to improve the detection of small invasive cancers and to reduce false-negative rates, even if this will lead to increasing referral rates.     

Screening ultrasonography revealed 15% of mammographically occult breast cancers

Background Mammography and physical examination (PE) are the recommended modalities for breast-cancer screening for women 40 years and older in Japan. Mammography, however, cannot detect lesions in dense breast tissue, which is common in Japanese women. Breast screening by ultrasound (US) is popular in Japan. We studied which modality or combinations of modalities optimize breast cancer detection for Japanese women. Methods From April 1993 through March 2005 we found 97 breast cancers in 9,082 women by screening examinations with mammography, US, and PE. We compared the detection rates of these three modalities for breast cancer. Results The detection rates of mammography, US, and PE for breast cancer were 83.5 (81 of 97 cancers), 75.3 (73 of 97 cancers), and 60.8% (59 of 97 cancers), respectively. The detection rates of the combinations of mammography and US, mammography and PE, and US and PE were 99.0 (96 of 97 cancers), 88.7 (86 of 97 cancers), and 81.4% (79 of 97 cancers), respectively. Ultrasonography detected 15% of the mammographically occult breast cancers. Conclusion Screening with the combination of mammography and US significantly increases the detection rate of breast cancer. These results suggest that screening with mammography and US would optimize cancer detection in Japanese women.     

Predicted long-term mortality reduction associated with the second round of breast screening in East Anglia

Randomized trials have demonstrated that mammographic screening can reduce breast cancer mortality. Our aim was to estimate the reduction in mortality expected from the East Anglian Breast Screening Programme. Breast screening achieves benefit by improving cancer prognosis (reducing tumour size, nodal involvement and possibly grade) through earlier diagnosis. We compared cancer prognosis between women invited for screening and those not yet invited in East Anglia, UK, in order to predict the mortality reduction achievable by screening, independently of any reduction due to changes in treatment and underlying disease. Participants (both invited and not-yet invited) were women eligible for invitation to first and second screens and diagnosed with invasive breast cancer in 1989-96. Death rates were predicted based on the observed distribution of tumour grade, size and node status amongst 950 cancers diagnosed following first invitation, up to and including at second screen (excluding those detected at first screening), and 451 cancers presenting symptomatically in women awaiting first invitation during the staggered introduction of screening, after adjustment for lead time amongst screen detected cases. For all ages, the ratio of predicted breast cancer mortality in the invited compared with the uninvited group was 0.85 (95% CI 0.78, 0.93). It was 0.93 (0.80, 1.08) for women aged 50-54 at diagnosis and 0.81 (0.72, 0.91) for those aged 55-64. We conclude that, by 2004, the second round of screening in East Anglia should reduce mortality by around 7% in women below age 55 at diagnosis, and by around 19% in those aged 55-64.     

Interval cancers as an indicator of perfomance in breast screening

BACKGROUND: The literature shows that breast screening performance varies between centers. Those who monitor the performance of screening programs must use appropriate methods to demonstrate quality. Analysis of interval cancer rates provides one such measure. This study analyses interval cancers over a ten-year period in a single center of the UK National Breast Screening Program, offering screening to a population of 45,000 women. METHODS: 108,948 screening examinations were undertaken between 1987 and 1996. Sequential interval cancer rates were studied and compared with the results of the Swedish Two-County trial. More detailed analysis of the first prevalence round was undertaken. RESULTS: Improvement in rates occurred after three years. Two-year time bands show some fluctuation in rates, indicating variation in performance. For one time period, rates equivalent to the Two County Trial were achieved, but this was not consistently maintained. Overall rates equate to performance reported elsewhere in the UK (25% in the first year after screening, 48% in the second year after screening and 48% in the third year after screening, equivalent Two County rates are 17%, 32% and 57%). The prevalence round analysis shows that undiagnosed cancers arose after the film reading stage in 88% of interval cases. The team was able to distinguish minor signs from significant lesions effectively. Assessment procedures were effective once the patient had been recalled. CONCLUSION: Interval cancer rates fell initially but reached a plateau. Recall procedures were effective in making the diagnosis, and cases were missed at the film reading stage. Consistency of performance may be important in achieving low rates.     

Short-term and long-term survival of interval breast cancers taking into account prognostic features

Purpose

The aim of this population-based study was to estimate short-term and long-term survival of interval breast cancers and to compare them to clinically detected cancers, taking into account prognostic features.

Methods

This study included all interval cancers and clinically detected cancers diagnosed in the Loire-Atlantique population-based cancer registry from 2000 to 2010 in women aged 50–76 years. We used the Pohar-Perme method to estimate 5- and 10 year net survival rates and a flexible parametric model to compare interval cancer and clinically detected cancer prognosis with and without adjustment for the main prognostic factors (age, stage, histological grade, and phenotype).

Results

This study included 813 interval cancers and 1,354 clinically detected cancers. Interval cancers were diagnosed at a significantly less advanced stage than clinically detected cancers, but more often with a triple-negative phenotype. Interval cancer age-standardised net survival was 88.0% at 5 years (95% CI 84.9–91.2) and 81.7% at 10 years (95% CI 76.9–86.9), whereas clinically detected cancer age-standardised net survival was 77.8% (95% CI 75.1–80.6) and 64.6% (95% CI 60.7–68.7), respectively. After adjustment for covariates, survival no longer differed between interval cancers and clinically detected cancers at 5 and 10 years.

Conclusion

Although the interval cancer net survival rate was higher, interval cancers had a similar short-term and long-term prognosis than clinically detected cancers after taking into account the main prognostic factors.

     

Mass Screening for Breast Cancer: Comparison of the Clinical Stages and Prognosis of Breast Cancer Detected by Mass Screening and in Out-patient Clinics

To establish the criteria for assessing the life-prolonging effect of mass screening for breast cancer, clinical stage and prognosis of breast cancer detected by mass screening in 11 regions of Japan were compared with those for matched patients in out-patient clinics. A total of 728 patients detected by mass screening and 1,450 found in the out-patient clinics were reviewed. The stage of the disease was Tis or I in 40.9% of the patients detected by mass screening, and 28.7% of those found in the out-patient clinics. In contrast, stage III was found in 9.3% and 14.6%, respectively, indicating that early stages were significantly more common in the patients detected by mass screening. The overall survival curve for the patients detected by mass screening was compared with that for those found in the out-patient clinics. The 5-year survival rate was significantly higher in the patients detected by mass screening (91.7% vs. 85.6%; P <0.01), while the 10-year survival rate was slightly higher in the same group of patients, but the difference from the other group was not significant (80.5% vs. 78.1%). Women who had conducted breast self-examination (BSE) showed a higher survival rate than those who had not conducted BSE.     

Mammographic density and survival in interval breast cancers

Introduction

Mammographic density (MD) is the strongest risk factor for breast cancer. It is also strongly associated with interval cancers (ICs) due to decreased screening sensitivity and possibly by also giving rise to more aggressive tumors. With this information as background, we compared survival in interval and screen-detected cancers, taking MD into consideration.

Methods

The patients were postmenopausal women ages 50 to 74 years who were diagnosed with breast cancer in Sweden between 1993 and 1995. A total of 1,115 women with screen-detected cancers and 285 with ICs had available mammograms. Cox proportional hazards models were used to compare breast cancer-specific survival between interval and screen-detected cancers stratified on MD.

Results

Hazard rates for breast cancer-specific survival were approximately three times higher in ICs than in screen-detected cancers, independent of MD. After adjustment for tumor size, a proxy for time to diagnosis, ICs in nondense breasts still had a statistically significantly increased hazard rate compared to screen-detected cancers in nondense breasts (5-yr survival hazard ratio (HR) 2.43, P = 0.001). In dense breasts, however, there was no longer evidence of a difference in survival between ICs and screen-detected cancers (5-yr survival HR 1.41, P = 0.486).

Conclusions

In nondense breasts, ICs seem to be truly more aggressive than screen-detected cancers. In dense breasts, the poorer prognosis of ICs compared to that of screen-detected cancers may be attributable at least partially to later detection. However, to the best of our knowledge, this study is the first to investigate these relationships, and further studies are warranted to confirm our results.     

Interval cancers in a French breast cancer-screening programme (Somme Department).

The objective of this study is to analyse the detection rates and tumour diameter of interval cancers in the breast cancer mass-screening programme of Somme Department (France), launched in 1990. Interval cancers are defined as breast cancers diagnosed within 36 months after a negative screening assessment, for women attending the programme between December 1990 to December 1993. Age-adjusted incidence rates were 0.51 per 1000 woman-years of follow-up in the 3-year interval after initial and subsequent screens. Diagnosis is made at early stage (sizes < or = 10 mm) in 20% of interval cancers. This stage is higher than that in screened women (9% of in situ cases and 35% of very small tumours). Interval cancer rates are low during the first year (0.18 per 1000 woman-years of follow-up) but higher in the second and third years.     

Interval cancers following breast cancer screening in Singaporean women

Our study reports on the interval cancers arising in the subsequent 3 years in women screened as part of the Singapore Breast Cancer Screening Programme that commenced in 1994. Women, the majority of Chinese ethnicity, were either invited or not invited by random allocation to be screened. All women, other than those identified with breast cancer at screening, whether invited or not, were followed for 3 years, and information on all breast cancers arising in this period was obtained through the national registry. In particular, the cancers arising from those women who were deemed free of the disease at screening were noted. The mammographs taken at screening of those women who developed such an interval cancer were rereviewed by 3 radiologists. In the 28,099 women who were screened and deemed free of disease, 59 interval cancers were reported with annual rates of 2.1, 10.6 and 10.8 per 10,000 women-years in the succeeding 3-year periods. In 39,425 women who were invited but declined screening, the rates were 17.0, 15.5 and 11.7, while the corresponding rates from 97,294 women not invited were 12.8, 13.3 and 13.0. Whereas the annual incidence at 1 year in women who have been screened is much lower than those in the 2 groups who were not screened, it is of a similar magnitude by 2 years. This suggests that locally an optimal screening interval may be close to 1 year. The rereview of the mammograms of those 59 women with interval cancers suggested that the maximum possible number of these that might have been detected at screening was 10 (17%).     

Analysis of interval breast carcinomas in a randomized screening trial in Stockholm

In the interval between screening examinations, some cases of breast cancer are invariably detected clinically in patients whose mammogram was considered to be normal at the earlier screening. During the first interval in the Stockholm study, 60 interval cancers were detected, giving a rate of 1.8 cases/1000 examinations/24 months. About half of these interval cases (31/60) were true interval tumours in that no sign of them could be found on the first mammogram; the other half, non-true, were possible to trace on the first mammogram. It is mainly women under 50 who feature in the interval group, above all in the sub-group of true interval cancers (p<0.05).The incidence of interval cancer rises, as expected, with the length of the interval (Fig. 1). In the final six months of the 2-year interval the incidence of interval cancers had risen to 88 per cent of the cancers detected in the control group in the same period of time.The cumulative incidence of interval cancers supports the hypothesis that the distribution of sojourn time in the interval 0–2 years is approximately rectangular. This means that shortening the interval by one-half would halve the number of interval cases.If mammography becomes a wide spread screening method for early detection of breast cancer, the number of non-true interval cancers could be a feed back on the effectiveness of the screening.An analysis of the malignancy of the true interval cancers, based on tumour size, axillary status, tumour stage, and estrogen receptor content, shows that these are the more malignant tumours with an unfavourable prognosis, while the control group is intermediate in this respect and the tumours detected at screening have the most favourable prognosis.     

The occurrence of interval cancers in the Nijmegen screening programme

Since January 1975 a population-based screening programme for the early detection of breast cancer has been carried out in the city of Nijmegen. During five interscreening periods of 2 years each a total of 158 so-called interval cancers were diagnosed. Careful revision of all screening and diagnostic mammograms was executed. Of all interval cancers 26% were 'missed' at the previous screening examination (due to technical or observer error), 16% were radiographically occult at the time of diagnosis and 58% were 'true' interval cancers. Interval cancers were regarded as 'true' when an obvious lesion was observed on the diagnostic mammogram while no suspect signs were seen on the previous screening mammogram. The prevalence of 'missed' cancers did not decline in the course of the screening programme. Radiographically occult tumours were localised, mostly in Wolfe's P2/DY breast parenchyma (83%), 33% were lobular invasive and 25% ductal non-invasive. 'True' interval cancer cases (58%) showed the same overall survival as control breast cancer patients, diagnosed in a non-screening situation. Shortening the screening interval would reduce interval cancer rates and probably further decrease breast cancer mortality in a screened population. However, from the present series of interval cancers 63% would not have been prevented by an annual screening examination. As regards women under age 50 annual screening would still leave 66% of all interval cancers in this age group undetected. Probably more benefit will be gained by searching for new imaging techniques to reduce numbers of 'missed' cancers and to detect lobular invasive and ductal non-invasive cancers in dense breast parenchyma.     

Current problems in mass screening for breast cancer

As the trend in the incidences of morbidity and mortality from breast cancer in Japan has been going up in recent years, mass screening for breast cancer is being undertaken on a nationwide scale. In Tokushima prefecture, 111,571 women (49,319 in actual number) were subjected to mass screening with physical examination from 1970-1984. In 116 including 26 cases of so-called "interval cancer", breast cancer was detected. Those with cancer detected by screening were in the earlier stage of the disease as compared to those diagnosed through regular medical care at our out-patient clinic during the same period. In the breast cancers detected by screening, the classifications of tumor size and lymph node involvement were not significantly different among the initial screening cases, subsequent screening cases and interval cases. The detection rate was 0.08% of total examinees, having 0.13% in the initial screening and 0.04% in the subsequent screening. The cancer was detectable mostly in patients aged over 60 and there were few cases in the younger generation. Repeat examinees accounted for 55.8% with an annual increase, but the proportion of initial examinees remained unchanged. Women in their 30s and 40s accounted for about 64.2% of all examinees. The results suggest that procedures such as inspection and palpation are useful for early detection of breast cancer among Japanese women. It is important to emphasize the following items for further improvement in our program, older women should be encouraged to actively participate in the screening, and percentage of initial examinees should be increased. Furthermore, the current objectives of mass screening for breast cancer are: to determine an appropriate screening survey method, to organize an adequate follow-up system for women with abnormal findings, and to educate the examinees in breast self-examination.     

Current status of screening for breast cancer and tasks for introduction of mammographic screening in Japan

In the United States and Europe the high mortality of breast cancer has been significantly reduced by mammographic screening of women aged over 50 years, the effectiveness of which has been documented in many reports. In contrast, the effectiveness of such screening in women aged from 40 to 49 remains controversial. In Japan, breast cancer screening has consisted of physical examination alone, with inspection and palpation. Thus, more than half of the patients with breast cancer detected by this screening system are already aware of their lumps, the detection rate has been a little less than 0.1%, and the proportion of early-stage disease among breast cancers is only about 50%. It is difficult to detect breast cancer consisting of non-palpable tumors by physical examination, and the low sensitivity of this screening method has been pointed out. In Japan, there is no difference in overall survival between cases detected by screening and those detected in outpatient clinics. The results of the mammographic screening trial performed in Miyagi and Tokushima, which were promising in terms of proportions of early-stage cancer and no nodal involvement, strongly suggest its usefulness in Japan as well as in other countries. However, long-term results are not yet available. It is advocated that screening for breast cancer should be performed by means of mammography to improve the screening sensitivity, and increase the proportion of early-stage breast cancers. Mammo-graphic screening, either mammography and physical examination separately or simultanously in combination, has been effective for women aged over 50 years in Japan. However, with regard to those aged under 49 years, further studies are needed.     

Pathological characteristics in screening versus clinically-detected breast cancer

We report pathological characteristics of screen detected breast cancers versus breast cancers diagnosed outside the official breast screening program. The breast cancer screening program was organised in the county of Haute-Vienne and a pathological record was established in the Association de dépistage des cancers du sein (ADCS 87). Three hundred and thirty three cases were recorded in 50 to 74 years-old women who had been screened (74 were interval cancers), six hundred and eighty seven in 50 to 74 years-old women without screening and three hundred and fifteen in women under 50. No difference in ductal carcinoma in situ or histological type was noted but tumor size and lymph node involvement presented significantly more favorable prognosis in screen detected breast cancers. This study confirms the potential benefit of screening in breast cancer.     

Breast density as a predictor of mammographic detection: comparison of interval- and screen-detected cancers

BACKGROUND: Screening mammography is the best method to reduce mortality from breast cancer, yet some breast cancers cannot be detected by mammography. Cancers diagnosed after a negative mammogram are known as interval cancers. This study investigated whether mammographic breast density is related to the risk of interval cancer. METHODS: Subjects were selected from women participating in mammographic screening from 1988 through 1993 in a large health maintenance organization based in Seattle, WA. Women were eligible for the study if they had been diagnosed with a first primary invasive breast cancer within 24 months of a screening mammogram and before a subsequent one. Interval cancer case subjects (n = 149) were women whose breast cancer occurred after a negative or benign mammographic assessment. Screen-detected control subjects (n = 388) were diagnosed after a positive screening mammogram. One radiologist, who was blinded to cancer status, assessed breast density by use of the American College of Radiology Breast Imaging Reporting and Data System. RESULTS: Mammographic sensitivity (i.e., the ability of mammography to detect a cancer) was 80% among women with predominantly fatty breasts but just 30% in women with extremely dense breasts. The odds ratio (OR) for interval cancer among women with extremely dense breasts was 6.14 (95% confidence interval [CI] = 1.95-19.4), compared with women with extremely fatty breasts, after adjustment for age at index mammogram, menopausal status, use of hormone replacement therapy, and body mass index. When only those interval cancer cases confirmed by retrospective review of index mammograms were considered, the OR increased to 9.47 (95% CI = 2.78-32.3). CONCLUSION: Mammographic breast density appears to be a major risk factor for interval cancer.     

Mitotic activity index in interval breast cancers.

AIMS: The Mitotic Activity Index (MAI) is a strong prognostic factor for disease free survival in breast cancer. The MAI is lower in screen detected tumours, correlating with less aggressive biological behaviour in this group. In this study the MAI is compared between screen detected, interval and symptomatic breast cancers. METHODS: Between 1991 and 1999, the MAI was determined in 581 breast cancers, 160 were detected by screening, 66 were interval carcinomas, and 355 were symptomatic breast cancers. Other prognostic factors were also registered. RESULTS: The interval group had a significantly higher median MAI (17-18, range 1-134) than the screen detected group (7-8, range 0-94,P <0.0001). There was no difference with the symptomatic group (MAI 15, range 0-149,P =0.92). CONCLUSIONS: Interval cancers had an intermediate outcome when correlated with other prognostic factors, compared to screen detected and symptomatic cancers.     

Quantification of the effect of mammographic screening on fatal breast cancers: The Florence Programme 1990-96

Breast cancer cases diagnosed in women aged 50-69 since 1990 to 1996 in the City of Florence were partitioned into those who had been invited to screening prior to diagnosis and those who had not. All cases were followed up for vital status until 31 December 1999. The cumulative number of breast cancer deaths among the cases were divided by screening and invitation status, to give the rates of cancers proving fatal within a period of 8 years of observation (incidence-based mortality). We used the incidence-based mortality rates for two periods (1985-86, 1990-96), pre and during screening. The incidence-based mortality ratio comparing 1990-96 and 1985-86 was 0.50 (95% CI : 0.38-0.66), a significant 50% reduction. For noninvited women, compared to 1985-86, there was a 41% significant mortality reduction (RR=0.59, 95% CI : 0.42-0.82). The comparable reduction in those invited was a significant 55% (RR=0.45, 95% CI : 0.32-0.61). The incidence ratio of rates of cancers stage II or worse was close to one when the noninvited in 1990-96 were compared with 1985-86 (RR=0.97, 95% CI : 0.78-1.21). Excluding prevalent cases, the rate of stage II+ breast cancer cases was 42% lower in Screened women compared with the noninvited (RR=0.58, 95% CI : 0.45-0.74). This study confirmed that new treatments and the first rounds of the screening programme contributed to reducing mortality from breast cancer.