Population-based Breast Cancer Screening Program Research Articles

Expression of thyroid transcription factor-1 is associated with a basal-like phenotype in breast carcinomas

BackgroundThe differential diagnosis between primary and secondary breast cancers might be difficult, especially in poorly differentiated tumors. Thyroid Transcription Factor-1 (TTF-1) has been regarded as a reliable marker for lung or thyroid origin, with only occasional positive staining in other tumors. However, positive cases have recently been reported among primary breast carcinomas.Methods and resultsHere, we analyzed expression of TTF-1 protein (clone SPT24) by immunohistochemical staining of sections from paraffin embedded tumor samples in 247 primary breast cancers from the population-based Norwegian Breast Cancer Screening Program. Positive staining (weak or strong) was observed in 7 cases (2,8%). As novel observations, positivity was demonstrated more frequently in estrogen receptor negative cases (14,0% vs. 1,4%; p = 0,004), highly proliferative tumors (8,8% vs. 1,1%; p = 0,008), tumors with a basal-like phenotype by showing expression of CK5/6 and/or P-cadherin (11,1% vs. 1,4%; p = 0,01), and tumors with blood vessel invasion (9,7% vs. 1,9%; p = 0,04). Also, TTF-1 was associated with histological grade 3 tumors compared with grade 1 or 2 tumors (7,7% vs. 1,5%; p = 0,04) as well as lymph node positive cases (5,2% vs. 1,8%; p = 0,03).ConclusionsOur population-based findings indicate that TTF-1 may be positive in approximately 3% of primary breast cancers, and positivity indicates an association with adverse prognostic factors.Virtual slidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/8313753509421182

Impact of hormone replacement therapy use on mammographic screening outcomes

This study aims to measure the impact of HRT use at the time of screening on rates of screen-detected invasive breast cancer (IBC) and ductal carcinoma in situ (DCIS), interval cancers and investigative procedures, within a well-established population-based mammography screening program. Using South Australian BreastScreen data from 1998 to 2009 pertaining to 819,722 screening episodes, Poisson regression models were undertaken to estimate the incidence risk ratios (IRR) for various screening outcomes at both the first and subsequent screening rounds, among women who had been using HRT in the 6 months prior to screening compared with those who had not. Current HRT use was associated with increased risk of recall for assessment, biopsy procedures, and breast cancer diagnosis among BreastScreen participants. Risk of screen-detected breast cancer was increased at subsequent screening rounds (IRR = 1.30, 95% confidence interval 1.18-1.34), but not at women's first screening round (1.05, 0.88-1.25). This increased risk applied to IBC (1.35, 1.27-1.45), but not to DCIS (1.04, 0.89-1.23). Interval cancer risk was elevated among HRT users following both the first screen (1.77, 1.33-2.37) and subsequent screening episodes (1.92, 1.72-2.15). Increased risks of recall, biopsy rates, screen-detected, and interval cancers among HRT users have important implications for population-based breast cancer screening programs. Our findings support the concept that HRT use may increase the growth of preexisting cancers. Lack of effect on DCIS could imply different etiology or time frames for DCIS and IBC development or increased transition from preinvasive to invasive disease due to HRT use.

Cumulative risk of cancer detection in breast cancer screening by protocol strategy

There is little information on the individual risk of screen-detected cancer in women over successive participations. This study aimed to estimate the 10-year cumulative breast cancer detection risk (ductal carcinoma in situ and invasive carcinoma) in a population-based breast cancer screening program according to distinct protocol strategies. A further aim was to determine which strategies maximized the cancer detection risk and how this risk was affected by the radiologic protocol variables. Data were drawn from a retrospective cohort of women from nine population-based screening programs in Spain from 1990 to 2006. We used logistic regression with discrete intervals to estimate the cumulative detection risk at 10 years of follow-up according to radiologic variables and protocol strategies. In women starting screening at the age of 45-59 years, the cumulative risk of screen-detected cancer at 10 years ranged from 11.11 to 16.71 per 1,000 participants according to the protocol strategy. The cumulative detection risk for overall cancer and invasive cancer was the highest with strategies using digital mammography, double reading, and two projections (16.71 and 12.07 ‰, respectively). For ductal carcinoma in situ, cumulative detection risk was the highest with strategies using screen-film, double reading, and two projections (2.32 ‰). The risk was the lowest with strategies using screen-film mammography, single reading, and two projections. This study found that at least eleven cancers are detected per 1,000 women screened in the first 10 years of follow-up. Enhanced knowledge of the variability in cumulative risk of screen-detected cancer could improve protocol strategies.

Recalibration of the Gail model for predicting invasive breast cancer risk in Spanish women: a population-based cohort study.

The Gail model for predicting the absolute risk of invasive breast cancer has been validated extensively in US populations, but its performance in the international setting remains uncertain. We evaluated the predictive accuracy of the Gail model in 54,649 Spanish women aged 45–68 years who were free of breast cancer at the 1996–1998 baseline mammographic examination in the population-based Navarre Breast Cancer Screening Program. Incident cases of invasive breast cancer and competing deaths were ascertained until the end of 2005 (average follow-up of 7.7 years) through linkage with population-based cancer and mortality registries. The Gail model was tested for calibration and discrimination in its original form and after recalibration to the lower breast cancer incidence and risk factor prevalence in the study cohort, and compared through cross-validation with a Navarre model fully developed from this cohort. The original Gail model overpredicted significantly the 835 cases of invasive breast cancer observed in the cohort (ratio of expected to observed cases 1.46, 95 % CI 1.36–1.56). The recalibrated Gail model was well calibrated overall (expected-to-observed ratio 1.00, 95 % CI 0.94–1.07), but it tended to underestimate risk for women in low-risk quintiles and to overestimate risk in high-risk quintiles (P = 0.01). The Navarre model showed good cross-validated calibration overall (expected-to-observed ratio 0.98, 95 % CI 0.92–1.05) and in different cohort subsets. The Navarre and Gail models had modest cross-validated discrimination indexes of 0.542 (95 % CI 0.521–0.564) and 0.544 (95 % CI 0.523–0.565), respectively. Although the original Gail model cannot be applied directly to populations with different underlying rates of invasive breast cancer, it can readily be recalibrated to provide unbiased estimates of absolute risk in such populations. Nevertheless, its limited discrimination ability at the individual level highlights the need to develop extended models with additional strong risk factors.Electronic supplementary materialThe online version of this article (doi:10.1007/s10549-013-2428-y) contains supplementary material, which is available to authorized users.

Development of acceptability criteria in mammography

Quality assurance protocols and standards of performance for X-ray mammography equipment are probably the most developed of any in the area of diagnostic radiology, due to the exacting demands on image quality required in population-based breast cancer screening programmes. Both qualitative and quantitative acceptability criteria have been published for X-ray mammography by considering the image quality needed clinically in screening programmes. Consequently, the task of developing a consensus for acceptability criteria appears to be relatively easy at first glance. However, there are two contentious issues that must be considered; the first is whether standards based on breast cancer screening can be transposed to equipment used for women referred for imaging with breast symptoms. The second relates to the use of image-quality assessment based upon the observation of details in test phantoms. In respect of the former, there was general agreement that only one set of acceptability criteria should apply to mammographic X-ray equipment. With regard to image-quality assessment, the weakness of the observer-based methods was recognised and a consensus position developed. This paper describes the development of a consensus on acceptability criteria and proposes both qualitative and quantitative criteria for use on all mammographic equipment. Some test approaches and criteria for image displays, in particular, were omitted from the document as concerns about their robustness emerged during the consultation phases of the revision. Clearly, further scientific work is needed in these areas.

Identifying specific non-attending groups in breast cancer screening - population-based registry study of participation and socio-demography

BackgroundA population-based breast cancer screening programme was implemented in the Central Denmark Region in 2008–09. The objective of this registry-based study was to examine the association between socio-demographic characteristics and screening participation and to examine whether the group of non-participants can be regarded as a homogeneous group of women.MethodParticipation status was obtained from a regional database for all women invited to the first screening round in the Central Denmark Region in 2008–2009 (n=149,234). Participation data was linked to registries containing socio-demographic information. Distance to screening site was calculated using ArcGIS. Participation was divided into ‘participants’ and ‘non-participants’, and non-participants were further stratified into ‘active non-participants’ and ‘passive non-participants’ based on whether the woman called and cancelled her participation or was a ‘no-show’.ResultsThe screening participation rate was 78.9%. In multivariate analyses, non-participation was associated with older age, immigrant status, low OECD-adjusted household income, high and low level education compared with middle level education, unemployment, being unmarried, distance to screening site >20 km, being a tenant and no access to a vehicle. Active and passive non-participants comprised two distinct groups with different socio-demographic characteristics, with passive non-participants being more socially deprived compared with active non-participants.ConclusionNon-participation was associated with low social status e.g. low income, unemployment, no access to vehicle and status as tenant. Non-participants were also more likely than participants to be older, single, and of non-Danish origin. Compared to active non-participants, passive non-participants were characterized by e.g. lower income and lower educational level. Different interventions might be warranted to increase participation in the two non-participant groups.

Inter- and intraradiologist variability in the BI-RADS assessment and breast density categories for screening mammograms

The aim of this study was to evaluate reader variability in screening mammograms according to the American College of Radiology Breast Imaging Reporting and Data System (BI-RADS) assessment and breast density categories. A stratified random sample of 100 mammograms was selected from a population-based breast cancer screening programme in Barcelona, Spain: 13 histopathologically confirmed breast cancers and 51 with true-negative and 36 with false-positive results. 21 expert radiologists from radiological units of breast cancer screening programmes in Catalonia, Spain, reviewed the mammography images twice within a 6-month interval. The readers described each mammography using BI-RADS assessment and breast density categories. Inter- and intraradiologist agreement was assessed using percentage of concordance and the kappa (κ) statistic. Fair interobserver agreement was observed for the BI-RADS assessment [κ=0.37, 95% confidence interval (CI) 0.36-0.38]. When the categories were collapsed in terms of whether additional evaluation was required (Categories III, 0, IV, V) or not (I and II), moderate agreement was found (κ=0.53, 95% CI 0.52-0.54). Intra-observer agreement for BI-RADS assessment was moderate using all categories (κ=0.53, 95% CI 0.50-0.55) and substantial on recall (κ=0.66, 95% CI 0.63-0.70). Regarding breast density, inter- and intraradiologist agreement was substantial (κ=0.73, 95% CI 0.72-0.74 and κ=0.69, 95% CI 0.68-0.70, respectively). We observed a substantial intra-observer agreement in the BI-RADS assessment but only moderate interobserver agreement. Both inter- and intra-observer agreement in mammographic interpretation of breast density was substantial. Advances in knowledge Educational efforts should be made to decrease radiologists' variability in BI-RADS assessment interpretation in population-based breast screening programmes.

E4. Current issues in breast cancer screening

E4. Current issues in breast cancer screening

Dutch digital breast cancer screening: implications for breast cancer care

In comparison to other European population-based breast cancer screening programmes, the Dutch programme has a low referral rate, similar breast cancer detection and a high breast cancer mortality reduction. The referral rate in the Netherlands has increased over time and is expected to rise further, mainly following nationwide introduction of digital mammography, completed in 2010. This study explores the consequences of the introduction of digital mammography on the balance between referral rate, detection of breast cancer, diagnostic work-up and associated costs. Detailed information on diagnostic work-up (chart review) was obtained from referred women (n = 988) in 2000-06 (100% analogue mammography) and 2007 (75% digital mammography) in Nijmegen, the Netherlands. The average referral rate increased from 15 (2000-06) to 34 (2007) per 1000 women screened. The number of breast cancers detected increased from 5.5 to 7.8 per 1000 screens, whereas the positive predictive value fell from 37% to 23%. A sharp rise in diagnostic work-up procedures and total diagnostic costs was seen. On the other hand, costs of a single work-up slightly decreased, as less surgical biopsies were performed. Our study shows that a low referral rate in combination with the introduction of digital mammography affects the balance between referral rate and detection rate and can substantially influence breast cancer care and associated costs. Referral rates in the Netherlands are now more comparable to other countries. This effect is therefore of value in countries where implementation of digital breast cancer screening has just started or is still under discussion.

A population-based breast cancer screening programme: conducting a comprehensive survey to explore adherence determinants

This research examines several important individual and environmental variables that can predict breast cancer screening practices among Portuguese women aged 45-69 years old, under a population-based programme. A cross-sectional study was conducted to a convenience sample with 805 women in Aveiro municipality. Survey interviews were applied to adherents and non-adherents in two different settings (health centre, home places). A combination of bivariate (chi-squared test) and multivariate analysis [decision tree by the chi-squared automatic interaction detection (CHAID) algorithm] was performed to determine differences between the groups and predict the variables. Findings showed that there is a significant association between almost all 29 indicators with adherence and non-adherence. Younger women (<50 years) with 'concordant' Behaviour Profile to the guidelines are those who adhere more in comparison with the other age groups. On the other hand, those with non-adherent behaviour need to have a 'good' attendance of healthcare providers for becoming adherents to the screening programme. Multiple strategies that combine enhancing primary health care access, individual behaviour and knowledge must be addressed to uptake adherence. In this way, the health teams must act in accordance with the guidelines, targeting more effective health education practices to achieve the goals of the breast cancer screening.

P1-309 Differences in radiological patterns, tumour characteristics and diagnostic precision between digital mammography and screen-film mammography in four breast cancer screening programs in Spain

IntroductionSince 2000 Digital Mammography (DM) has been commercially available and implemented in many breast cancer screening programs. Although available information suggests that differences, if exist, are low, complete evaluation of...

P1-283 Trends in age at menarche and menopause of women in Valencia community born in during 1927–1964 period

ObjectiveTo describe and analyse the trend in age at menarche and menopause of women who have attended the breast cancer-screening program in the Valencian Community (VC) from 1992 to 2009...

Effect of radiologist experience on the risk of false-positive results in breast cancer screening programs

To evaluate the effect of radiologist experience on the risk of false-positive results in population-based breast cancer screening programmes. We evaluated 1,440,384 single-read screening mammograms, corresponding to 471,112 women aged 45-69 years participating in four Spanish programmes between 1990 and 2006. The mammograms were interpreted by 72 radiologists. The overall percentage of false-positive results was 5.85% and that for false-positives resulting in an invasive procedure was 0.38%. Both the risk of false-positives overall and of false-positives leading to an invasive procedure significantly decreased (p < 0.001) with greater reading volume in the previous year: OR 0.77 and OR 0.78, respectively, for a reading volume 500-1,999 mammograms and OR 0.59 and OR 0.60 for a reading volume of >14,999 mammograms with respect to the reference category (<500). The risk of both categories of false-positives was also significantly reduced (p < 0.001) as radiologists' years of experience increased: OR 0.96 and OR 0.84, respectively, for 1 year's experience and OR 0.72 and OR 0.73, respectively, for more than 4 years' experience with regard to the category of <1 year's experience. Radiologist experience is a determining factor in the risk of a false-positive result in breast cancer screening.

Differences in radiological patterns, tumour characteristics and diagnostic precision between digital mammography and screen-film mammography in four breast cancer screening programmes in Spain

To compare tumour characteristics between cancers detected with screen-film mammography (SFM) and digital mammography (DM) and to evaluate changes in positive predictive values (PPVs) for further assessments, for invasive procedures and for distinct radiological patterns in recalled women. 242,838 screening mammograms (171,191 SFM and 71,647 DM) from 103,613 women aged 45-69 years, performed in four population-based breast cancer screening programmes in Spain, were included. The tumour characteristics and PPVs of each group were compared. Radiological patterns (masses, calcifications, distortions and asymmetries) among recalled women were described and PPVs were evaluated. The percentages of ductal carcinoma in situ (DCIS) were higher in DM than in SFM both in the first [18.5% vs. 15.8%(p = 0.580)] and in successive screenings [23.2% vs. 15.7%(p = 0.115)]. PPVs for masses, asymmetries and calcifications were higher in DM, being statistically significant in masses (5.3% vs. 3.9%; proportion ratio: 1.37 95%CI: 1.08-1.72). Among cancers detected by calcifications, the percentage of DCIS was higher in DM (60.3% vs. 46.4%, p = 0.060). PPVs were higher when DM was used, both for further assessments and for invasive procedures, with similar cancer detection rates and no statistically significant differences in tumour characteristics. The greatest improvements in PPVs were found for masses.

Effect of false-positive results on reattendance at breast cancer screening programmes in Spain

Mammography is the only breast screening method, we are aware of today, which is able to reduce mortality from breast cancer. Nevertheless, this procedure carries an inherent risk of false-positive screening mammogram. The association between these results and reattendance at the next scheduled screening mammogram is controversial. The aim of this study was to examine the effect of a false-positive screening mammogram and women's characteristics on reattendance in eight regional population-based breast cancer screening programmes in Spain. This study included 1 383 032 women aged 44-67 years who were initially screened for breast cancer between 1990 and 2004. To investigate factors associated with reattendance, logistic regression models were used. The mean age of women at first screening was 53.6 years (SD = 6.1 years). Of 120 800 women with a false-positive screening mammogram, 78.3% returned for a subsequent screening mammogram compared with 81.9% of those with a negative result (P < 0.001). Multivariate analysis showed that women with a false-positive result at first screening mammogram were less likely to reattend (OR = 0.71; 95% CI 0.70-0.73) and that the likelihood was lower in those who had undergone invasive additional tests (OR = 0.56; 95% CI 0.53-0.59). A false-positive screening mammogram in the first screening negatively affected attendance at the subsequent screening. The results of this study could be useful to improve the screening process and to increase women's compliance.

Reduction in False-Positive Results after Introduction of Digital Mammography: Analysis from Four Population-based Breast Cancer Screening Programs in Spain

To evaluate the effect of the introduction of digital mammography on the recall rate, detection rate, false-positive rate, and rates of invasive procedures in a cohort of women from four population-based breast cancer screening programs in Spain. The study was approved by the ethics committee; informed consent was not required. A total of 242,838 mammograms (171,191 screen film [screen-film mammography group] and 71,647 digital [digital mammography group]) obtained in 103,613 women aged 45-69 years were included. False-positive results for any additional procedure and for invasive procedures, the breast cancer rate, and the positive predictive value in each group were compared by using Pearson χ(2) test. The effect of the mammographic technology used (screen-film or digital) on the false-positive results and cancer detection risk was evaluated with multivariate logistic regression models, adjusted according to women's and the screening program's characteristics and time trends. The false-positive rate was higher for screen-film than for digital mammography (7.6% and 5.7%, respectively; P < .001). False-positive results after an invasive procedure were significantly higher for screen-film than for digital mammography (1.9% and 0.7%, respectively; P < .001). No significant differences were observed in the overall cancer detection rate between the two groups (0.45% and 0.43% in the screen-film and digital mammography groups, respectively; P = .59). The adjusted risk of a false-positive result was higher for screen-film than for digital mammography (odds ratio = 1.32). The adjusted risk was also lower for the digital mammography group when time trends were taken into account. The lower false-positive risk with use of digital mammography should be taken into account when balancing the risks and benefits of breast cancer screening.

Urban-rural differences in a population-based breast cancer screening program in Croatia.

AimTo investigate urban-rural differences in the distribution of risk factors for breast cancer.MethodsWe analyzed the data from the first round of the “Mamma” population based-screening program conducted in Croatia between 2007 and 2009 and self-reported questionnaire results for 924 patients with histologically verified breast cancer. Reproductive and anthropometric characteristics, family history of breast cancer, history of breast disease, and prior breast screening history were compared between participants from the city of Zagreb (n = 270) and participants from 13 counties with more than 50% of rural inhabitants (n = 654).ResultsThe screen-detected breast cancer rate was 4.5 per 1000 mammographies in rural counties and 4.6 in the city of Zagreb, while the participation rate was 61% in rural counties and 59% in Zagreb. Women from Zagreb had significantly more characteristics associated with an increased risk of breast cancer (P < 0.001 in all cases): no pregnancies (15% vs 7%), late age of first pregnancy (≥30 years) (10% vs 4%), and the most recent mammogram conducted 2-3 years ago (32% vs 14%). Women from rural counties were more often obese (41% vs 28%) and had early age of first live birth (<20 years) (20% vs 7%, P < 0.001 for both).ConclusionIdentification of rural-urban differences in mammography use and their causes at the population level can be useful in designing and implementing interventions targeted at the reduction of inequalities and modifiable risk factors.

Variation in mammographic appearance between projections of small breast cancers compared with radial scars

The study aims to assess variation in appearance between mammographic projections (conspicuity variation) for invasive breast cancers (IBCs) compared with radial scars (RS). Conspicuity variation has been previously described as characteristic of RS. The lesions were also compared with respect to breast density and the proportion of cases detected by one of two readers and required a third (consensus) read. The study was approved by the BreastScreen Victoria research committee. Mammograms of 75 randomly selected invasive breast cancers, with histological diameter ≤10 mm (IBC), were mixed with 67 consecutively detected RS, all from a double-reading population-based breast cancer screening programme. On blinded review, these 142 lesions were classified for mammographic findings and assessed for marked or minor conspicuity variation between views. We assessed the associations between lesion type, lesion spicules and centres, breast density, conspicuity variation and proportion detected by one reader only. Marked conspicuity variation was common, but not statistically different for IBC and RS (64% vs. 66%, χ(2) = 0.8, P = 0.04). Conspicuity variation did not correlate with spiculation type (long, fine or short, broad based) or lesion centres (lucent or dense) (ρ < 0.05, P = 0.5), and showed no significant change with increasing Breast Imaging Reporting and Data System breast density (IBC, χ(2) = 2.3, P = 0.5; RS, χ(2) = 0.95, P = 0.6). Density did not vary by lesion type. In the screening programme, 29% of IBC (125 of 431) versus 43% of RS (32 of 75) had been detected by one of two readers (χ(2) = 2.7, P = 0.098). Two-thirds of small IBCs displayed marked conspicuity variation, similar to RS. Therefore, conspicuity variation does not discriminate between IBC and RS.

Breast and cervical cancer screening programme implementation in 16 countries

There is a continuing need to monitor and evaluate the impact of organized screening programmes on cancer incidence and mortality. We report results from a programme assessment conducted within the International Cancer Screening Network (ICSN) to understand the characteristics of cervical screening programmes within countries that have established population-based breast cancer screening programmes. In 2007-2008, we asked 26 ICSN country representatives to complete a web-based survey that included questions on breast and cervical cancer screening programmes. We summarized information from 16 countries with both types of organized programmes. In 63% of these countries, the organization of the cervical cancer screening programme was similar to that of the breast cancer screening programme in the same country. There were differences in programme characteristics, including year established (1962-2003 cervical; 1986-2002 breast) and ages covered (15-70+ cervical; 40-75+ breast). Adoption of new screening technologies was evident (44% liquid-based Pap tests; 13% human papillomavirus (HPV)-triage tests cervical; 56% digital mammography breast). There was wide variation in participation rates for both programme types (<4-80% cervical; 12-88% breast), and participation rates tended to be higher for cervical (70-80%) than for breast (60-70%) cancer screening programmes. Eleven ICSN member countries had approved the HPV vaccine and five more were considering its use in their organized programmes. Overall, there were similarities and differences in the organization of breast and cervical cancer screening programmes among ICSN countries. This assessment can assist established and new screening programmes in understanding the organization and structure of cancer screening programmes.

The first national public breast cancer screening program in Saudi Arabia

BACKGROUND AND OBJECTIVES:Despite its relatively low incidence in Saudi Arabia, breast cancer has been the most common cancer among Saudi females for the past 12 consecutive years. The objective of this study was to report the results of the first national public breast cancer screening program in Saudi Arabia.METHODS:Women 40 years of age or older underwent breast cancer screening. Mammograms were scored using the Breast Imaging-Reporting and Data System (BI-RADS). Correlations between imaging findings, risk factors and pathological findings were analyzed.RESULTS:Between September 2007 and April 2008, 1215 women were enrolled. The median age was 45 years, and median body mass index was 31.6 kg/m2. Sixteen cases of cancer were diagnosed. No cancer was diagnosed in 942 women with R1/R2 scores, and only 1 case of cancer was diagnosed in 228 women with R0/R3 scores. However, among 26 women with R4/R5 scores, 50% had malignant disease and 35% had benign lesions. No correlation was found between known risk factors and imaging score or cancer diagnosis.CONCLUSIONS:Public acceptance of the breast cancer screening program was encouraging. Longitudinal follow-up will help in better determining the risk factors relevant to our patient population.