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Objectives: To evaluate the mammographic features in women with benign breast disease (BBD) and the risk of subsequent breast cancer according to their mammographic findings., Methods: We analyzed data from a Spanish cohort of women screened from 1995 to 2015 and followed up until December 2017 (median follow-up, 5.9 years). We included 10,650 women who had both histologically confirmed BBD and mammographic findings. We evaluated proliferative and nonproliferative BBD subtypes, and their mammographic features: architectural distortion, asymmetries, calcifications, masses, and multiple findings. The adjusted hazard ratios (aHR) and 95% confidence intervals (95% CI) for breast cancer were estimated using a Cox proportional hazards model. We plotted the adjusted cumulative incidence curves., Results: Calcifications were more frequent in proliferative disease with atypia (43.9%) than without atypia (36.8%) or nonproliferative disease (22.2%; p value < 0.05). Masses were more frequent in nonproliferative lesions (59.1%) than in proliferative lesions without atypia (35.1%) or with atypia (30.0%; p value < 0.05). Multiple findings and architectural distortion were more likely in proliferative disease (16.1% and 4.7%) than in nonproliferative disease (12.8% and 1.9%). Subsequent breast cancer occurred in 268 (2.5%) women. Compared with women who had masses, the highest risk of subsequent breast cancer was found in those with architectural distortions (aHR, 2.21; 95% CI, 1.16-4.22), followed by those with multiple findings (aHR, 1.89; 95% CI, 1.34-2.66), asymmetries (aHR, 1.66; 95% CI, 0.84-3.28), and calcifications (aHR, 1.60; 95% CI, 1.21-2.12)., Conclusion: BBD subtypes showed distinct mammographic findings. The risk of subsequent breast cancer was high in those who have shown architectural distortion, multiple findings, asymmetries, and calcifications than in women with masses., Key Points: • The presence of mammographic findings in women attending breast cancer screening helps clinicians to assess women with benign breast disease (BBD). • Calcifications were frequent in BBDs with atypia, which are the ones with a high breast cancer risk, while masses were common in low-risk BBDs. • The excess risk of subsequent breast cancer in women with BBD was higher in those who showed architectural distortion compared to those with masses., (© 2021. European Society of Radiology.)

Background: Several studies have proposed personalized strategies based on women's individual breast cancer risk to improve the effectiveness of breast cancer screening. We designed and internally validated an individualized risk prediction model for women eligible for mammography screening., Methods: Retrospective cohort study of 121,969 women aged 50 to 69 years, screened at the long-standing population-based screening program in Spain between 1995 and 2015 and followed up until 2017. We used partly conditional Cox proportional hazards regression to estimate the adjusted hazard ratios (aHR) and individual risks for age, family history of breast cancer, previous benign breast disease, and previous mammographic features. We internally validated our model with the expected-to-observed ratio and the area under the receiver operating characteristic curve., Results: During a mean follow-up of 7.5 years, 2,058 women were diagnosed with breast cancer. All three risk factors were strongly associated with breast cancer risk, with the highest risk being found among women with family history of breast cancer (aHR: 1.67), a proliferative benign breast disease (aHR: 3.02) and previous calcifications (aHR: 2.52). The model was well calibrated overall (expected-to-observed ratio ranging from 0.99 at 2 years to 1.02 at 20 years) but slightly overestimated the risk in women with proliferative benign breast disease. The area under the receiver operating characteristic curve ranged from 58.7% to 64.7%, depending of the time horizon selected., Conclusions: We developed a risk prediction model to estimate the short- and long-term risk of breast cancer in women eligible for mammography screening using information routinely reported at screening participation. The model could help to guiding individualized screening strategies aimed at improving the risk-benefit balance of mammography screening programs., Competing Interests: The authors have declared that no competing interests exist.

Objective: We aimed to explore whether the type of mammographic feature prompting a false-positive recall (FPR) during mammography screening influences the risk and timing of breast cancer diagnosis, particularly if assessed with invasive procedures., Study Design: We included information on women screened and recalled for further assessment in Spain between 1994 and 2015, with follow-up until 2017, categorizing FPRs by the assessment (noninvasive or invasive) and mammographic feature prompting the recall., Main Outcome Measures: Breast cancer rates in the first two years after FPR (first period) and after two years (second period)., Results: The study included 99,825 women with FPRs. In both periods, the breast cancer rate was higher in the invasive assessment group than in the noninvasive group (first period 12 ‰ vs 1.9 ‰, p < 0.001; second period 4.4‰ vs 3.1‰, p < 0.001). During the first period, the invasive assessment group showed diverse breast cancer rates for each type of mammographic feature, with a higher rate for asymmetric density (31.9‰). When the second period was compared with the first, the breast cancer rate decreased in the invasive assessment group (from 12‰ to 4.4‰, p < 0.001) and increased in the noninvasive assessment group (from 1.9‰ to 3.1‰, p < 0.001)., Conclusion: In the context of mammography screening, the risk of breast cancer diagnosis during the first two years after FPR was particularly high for women undergoing invasive assessment; importantly, the risk was modified by type of mammographic feature prompting the recall. This information could help to individualize follow-up after exclusion of malignancy., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: We aimed to identify the risk factors associated with early, late and long-term readmissions in women diagnosed with breast cancer participating in screening programs., Methods: We performed a multicenter cohort study of 1055 women aged 50-69 years participating in Spanish screening programs, diagnosed with breast cancer between 2000 and 2009, and followed up to 2014. Readmission was defined as a hospital admission related to the disease and/or treatment complications, and was classified as early (< 30 days), late (30 days-1 year), or long-term readmission (> 1 year). We used logistic regression to estimate the adjusted odds ratios (aOR), and 95% confidence intervals (95% CI) to explore the factors associated with early, late and long-term readmissions, adjusting by women's and tumor characteristics, detection mode, treatments received, and surgical and medical complications., Results: Among the women included, early readmission occurred in 76 (7.2%), late readmission in 87 (8.2%), long-term readmission in 71 (6.7%), and no readmission in 821 (77.8%). Surgical complications were associated with an increased risk of early readmissions (aOR = 3.62; 95%CI: 1.27-10.29), and medical complications with late readmissions (aOR = 8.72; 95%CI: 2.83-26.86) and long-term readmissions (aOR = 4.79; 95%CI: 1.41-16.31)., Conclusion: Our results suggest that the presence of surgical or medical complications increases readmission risk, taking into account the detection mode and treatments received. Identifying early complications related to an increased risk of readmission could be useful to adapt the management of patients and reduce further readmissions., Trial Registration: ClinicalTrials.govIdentifier: NCT03165006. Registration date: May 22, 2017 (Retrospectively registered).

Background: The effect of changes in mammographic density over time on the risk of breast cancer remains inconclusive., Methods: We used information from four centres of the Breast Cancer Screening Program in Spain in the period 1996-2015. We analysed individual level data from 117,388 women first screened age 50-54, with at least two screening examinations. Breast density was determined using the BI-RADS classification (A to D in increasing order) at earliest and latest screening examination. Adjusted Poisson regression models were used to estimate the relative risk (RR) and 95% confidence intervals (95%CI) of the association between changes in mammographic density and breast cancer risk over time., Results: During an average 5.8 years of follow-up, 1592 (1.36%) women had a breast cancer diagnosis. An increase in density category increased breast cancer risk, and a decrease in density decreased the risk, compared with women who remained in the same BI-RADS category. Women whose density category increased from B to C or B to D had a RR of 1.55 (95%CI = 1.24-1.94) and 2.32 (95%CI = 1.48-3.63), respectively. The RR for women whose density increased from C to D was 1.51 (95%CI = 1.03-2.22). Changes in BI-RADS density were similarly associated with the risk for invasive cancer than for ductal carcinoma in situ., Conclusions: Although a modest proportion of women changed BI-RADS density category, mammographic density changes modulated the risk of breast cancer and identified women at a differential risk. Using two longitudinal measures of BI-RADS density could help target women for risk-based screening strategies., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Introduction: Currently, variability in surgical practice is a problem to be solved. The aim of this study is to describe the variability in the surgical treatment of breast cancer and to analyze the factors associated with it., Methods: The study population included 1057 women diagnosed with breast cancer and surgically treated. Our data were from the CaMISS retrospective cohort., Results: The mean age at diagnosis was 59.3 ± 5 years. A total of 732 patients were diagnosed through screening mammograms and 325 patients as interval cancers. The mastectomy surgery was more frequent in the tumors detected between intervals (OR=2.5; [95%CI: 1.8-3.4]), although this effect disappeared when we adjusted for the rest of the variables. The most important factor associated with performing a mastectomy was TNM: tumors in stage III-IV had an OR of 7.4 [95%CI: 3.9-13.8], increasing in adjusted OR to 21.7 [95%CI: 11.4-41.8]. Histologically, infiltrating lobular carcinoma maintains significance in adjusted OR (OR=2.5; [95%CI: 1.4-4.7]). According to the screening program, there were significant differences in surgical treatment. Program 3 presented an OR of non-conservative surgery of 4.0 [95%CI: 1.8-8.9]. This program coincided with the highest percentage of reconstruction (58.3%)., Conclusions: This study shows that, despite taking into account patient and tumor characteristics, there is great variability in the type of surgery depending on the place of diagnosis., (Copyright © 2018 AEC. Publicado por Elsevier España, S.L.U. All rights reserved.)

Objectives: To investigate how breast density affects screening performance indicators in a digital mammography context., Methods: We assessed the effect of breast density over the screen-detected and interval cancers rates, false-positives, specificity, sensitivity, recall rate, positive predictive value of recall (PPV-1), and PPV of invasive tests (PPV-2). Radiologists classified breast density using the BIRADS System. We used generalized estimating equations to account for within-woman correlation by means of the robust Huber-White variance estimator., Results: We included 177,164 women aged 50-69 years who underwent 499,251 digital mammograms from 2004 to 2015 in Spain. According to the fibroglandular tissue percentage, 24.7% of mammograms were classified as BI-RADS 1 (<25% glandular), 54.7% as BI-RADS 2 (25-50% glandular), 14.0% as BI-RADS 3 (51-75% glandular) and 6.6% as BI-RADS 4 (>75% glandular). Overall, women with BI-RADS 3 had the highest screen-detected cancer rate (5.9 per 1000) and BI-RADS 4 the highest interval cancer rate (2.4 per 1000). Sensitivity decreased from 89.2% in women with BI-RADS 1 to 67.9% in BI-RADS 4. Both PPV-1 and PPV-2 decreased from 10.4% to 5.7% and from 49.8% to 32.4% in women with BI-RADS 1 and BI-RADS 4, respectively. Women aged 60-69 years with BI-RADS 4 had the lowest sensitivity (54.9%) and the highest interval cancer rate (3.8 per 1000)., Conclusions: Performance screening measures are negatively affected by breast density falling to a lower sensitivity and PPV, and higher interval cancer rate as breast density increases. Particularly women aged 60-69 years with >75% glandular breasts had the worst results and therefore may be candidates for screening using other technologies., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: We aimed to evaluate survival and disease-free survival in different subtypes of interval cancers by breast density, taking into account clinical and biological characteristics. Methods: We included 374 invasive breast tumors (195 screen-detected cancers; 179 interval cancers, classified into true interval, false-negatives, occult tumors and minimal-sign cancers) diagnosed in women ages 50-69 years undergoing biennial screening from 2000-2009, followed up to 2014. Breast density was categorized into non-dense (<25% dense tissue) and mixed dense breasts (≥25%). Survival curves were generated by the Kaplan-Meier method and compared by the log-rank test. Cox proportional hazard regression models were computed to estimate the adjusted hazard ratios (aHRs) and 95% confidence intervals (95% CIs) for death and recurrences by comparing women with interval and true interval cancers versus women with screen-detected cancers, controlling for tumor and patient characteristics. All analyses were stratified by breast density. Results: Interval cancers were detected in younger women, at more advanced stages, in denser breasts and showed a higher proportion of triple-negative cancers, especially among true interval cancers. Women with interval cancer and non-dense breasts had an aHR for death of 3.40 (95% CI, 0.92-12.62). Women with true interval cancers detected in non-dense breasts had the highest adjusted risk of death (aHR, 6.55; 95% CI, 1.37-31.39). Conclusions: Women with true interval cancer in non-dense breasts had a higher risk of death than women with screen-detected cancers. Impact: These results support the advisability of routinely collecting information on breast density, both for further tailoring of screening strategies and as a prognostic factor for diagnosed breast cancers. Cancer Epidemiol Biomarkers Prev; 27(8); 908-16. ©2018 AACR ., (©2018 American Association for Cancer Research.)

Women with a benign breast disease (BBD) have an increased risk of subsequent breast carcinoma. Information is scarce regarding the characteristics of breast carcinomas diagnosed after a BBD. Our aim was to point out the differences in clinical and histologic characteristics of breast carcinomas diagnosed in women with and without a previous pathologic diagnosis of BBD in the context of population-based mammography screening. Retrospective cohort study of all women aged 50-69 years who were screened at least once in a population-based screening program in Spain, between 1994 and 2011 and followed up until December 2012. The mean follow-up was 6.1 years. We analyzed 6645 breast carcinomas, of whom 238 had a previous pathologic diagnosis of BBD. Information on clinical and histologic characteristics was collected from pathology reports. Logistic regression was used to estimate the odds ratio (OR) and 95% confidence intervals (95%CI) of occurrence of selected histologic characteristics of breast carcinomas in women with and without a previous BBD. Women with a previous BBD had a higher proportion of ductal carcinoma in situ (DCIS) compared with women without a BBD (22.1% and 13.6%, respectively). Among those diagnosed with an invasive breast carcinoma, women with previous BBD were more likely to be diagnosed with carcinomas sized >2 cm (OR = 1.46; 95%CI = 1.03-2.08), metastatic positive (OR = 2.66; 95%CI = 1.21-5.86), and with a high Ki-67 proliferation rate (OR = 1.93; 95%CI = 1.24-2.99). No differences were found across histologic subtypes of BBD. Screening participants with a previous pathologic diagnosis of BBD had a higher proportion of DCIS. However, invasive carcinomas detected in women with a BBD were associated with clinical and histologic characteristics conferring a worst prognosis., (© 2018 Wiley Periodicals, Inc.)

We propose a joint model to analyze the structure and intensity of the association between longitudinal measurements of an ordinal marker and time to a relevant event. The longitudinal process is defined in terms of a proportional-odds cumulative logit model. Time-to-event is modeled through a left-truncated proportional-hazards model, which incorporates information of the longitudinal marker as well as baseline covariates. Both longitudinal and survival processes are connected by means of a common vector of random effects. General inferences are discussed under the Bayesian approach and include the posterior distribution of the probabilities associated to each longitudinal category and the assessment of the impact of the baseline covariates and the longitudinal marker on the hazard function. The flexibility provided by the joint model makes possible to dynamically estimate individual event-free probabilities and predict future longitudinal marker values. The model is applied to the assessment of breast cancer risk in women attending a population-based screening program. The longitudinal ordinal marker is mammographic breast density measured with the Breast Imaging Reporting and Data System (BI-RADS) scale in biennial screening exams. © 2016 The Authors. Statistics in Medicine Published by John Wiley & Sons Ltd., (© 2016 The Authors. Statistics in Medicine Published by John Wiley & Sons Ltd.)

Background: To date, the study of the risks and benefits of breast cancer screening has not included the onset of persistent pain after breast cancer treatment within the context of population-based screening programs. Our purpose was to investigate the prevalence of persistent pain and associated factors in women diagnosed with breast cancer (screening or interval) in the context of a population-based breast cancer screening program in Spain., Methods: A total of 1,057 women participating in a population-based breast cancer screening program were diagnosed with breast cancer between 2000 and 2008. The women were treated surgically and followed-up to 2013. The risk of developing persistent pain was estimated through multivariate logistic regression analysis., Results: Breast cancer was detected during routine screening in 732 women (69.3 %) and emerged as an interval cancer between two screening rounds in 325 (30.7 %). Persistent pain was present in 118 women (11.3 %). Women diagnosed through routine screening reported a higher prevalence of persistent pain (12.9 %) than those with interval cancers (7.8 %)(P < 0.05). Multivariate logistic regression analysis identified two other variables associated with persistent pain: having a Charlson index > =2 (Odds Ratio [OR]: 4.5 95 % Confidence Interval [CI]: 2.1-9.5) versus no comorbidities, and having undergone an axillary lymph node dissection (OR: 2.0 95 % CI: 1.0-4.0) versus sentinel lymph node biopsy., Conclusions: The prevalence of persistent pain was relatively low. The detection mode was not related to the onset of persistent pain. The factors associated with persistent pain were a Charlson index > =2 and the performance of axillary lymph node dissection. Women treated for breast cancer are at risk for developing persistent pain regardless of the detection mode, especially those with comorbidities and those who have undergone axillary lymph node dissection.

Purpose To assess the risk of breast cancer in women with false-positive screening results according to radiologic classification of mammographic features. Materials and Methods Review board approval was obtained, with waiver of informed consent. This retrospective cohort study included 521 200 women aged 50-69 years who underwent screening as part of the Spanish Breast Cancer Screening Program between 1994 and 2010 and who were observed until December 2012. Cox proportional hazards regression analysis was used to estimate the age-adjusted hazard ratio (HR) of breast cancer and the 95% confidence interval (CI) in women with false-positive mammograms as compared with women with negative mammograms. Separate models were adjusted for screen-detected and interval cancers and for screen-film and digital mammography. Time without a breast cancer diagnosis was plotted by using Kaplan-Meier curves. Results When compared with women with negative mammograms, the age-adjusted HR of cancer in women with false-positive results was 1.84 (95% CI: 1.73, 1.95; P < .001). The risk was higher in women who had calcifications, whether they were (HR, 2.73; 95% CI: 2.28, 3.28; P < .001) or were not (HR, 2.24; 95% CI: 2.02, 2.48; P < .001) associated with masses. Women in whom mammographic features showed changes in subsequent false-positive results were those who had the highest risk (HR, 9.13; 95% CI: 8.28, 10.07; P < .001). Conclusion Women with false-positive results had an increased risk of breast cancer, particularly women who had calcifications at mammography. Women who had more than one examination with false-positive findings and in whom the mammographic features changed over time had a highly increased risk of breast cancer. Previous mammographic features might yield useful information for further risk-prediction models and personalized follow-up screening protocols. (©) RSNA, 2016 Online supplemental material is available for this article.

In the context of a population-based screening program, we aimed to evaluate the major mammographic features and clinicopathological characteristics of breast tumors at diagnosis and the associations between them, focusing on tumors with the worst prognosis. We analyzed cancers diagnosed in a cohort of 645,764 women aged 45-69 years participating in seven population-based screening programs in Spain, between January 1, 2000 and December 31, 2006 and followed up until June 2009. We included all interval cancers and a sample of screen-detected cancers, whether invasive or in situ. We compared tumor-related information and breast density for different phenotypes (Triple-negative (TN), HER2+, Luminal B and Luminal A) in screen-detected and interval cancers. We used Chi-square or Fisher's exact test to compare major mammographic features of invasive versus in situ tumors, of screen-detected versus interval cancers, and of different types of interval cancers. We included 2582 tumors (1570 screen-detected and 1012 interval cancers). There were significant differences in the distribution of most clinicopathological variables between screen-detected and interval cancers. Invasive TN interval tumors were more common than other phenotypes in breasts with low mammographic density; three-quarters of these tumors presented as masses without associated calcifications. HER2+ tumors were more common in denser breasts and were associated with calcifications and multifocality. Architectural distortion was more common in Luminal A and Luminal B tumors. Certain radiologic findings are associated with pre-invasive lesions; these differ among invasive tumor phenotypes. We corroborate that TN and HER2+ cancers have distinctive appearances also in the context of population-based screening programs. This information can be useful for establishing protocols for diagnostic strategies in screening units.

Purpose: To evaluate the correlations of maximum stiffness (Emax) and mean stiffness (Emean) of invasive carcinomas on shear-wave elastography (SWE) with St. Gallen consensus tumor phenotypes., Methods: We used an ultrasound system with SWE capabilities to prospectively study 190 women with 216 histologically confirmed invasive breast cancers. We obtained one elastogram for each lesion. We correlated Emax and Emean with tumor size, histologic type and grade, estrogen and progesterone receptors, HER2 expression, the Ki67 proliferation index, and the five St. Gallen molecular subtypes: luminal A, luminal B without HER2 overexpression (luminal B HER2-), luminal B with HER2 overexpression (luminal B HER2+), HER2, and triple negative., Results: Lesions larger than 20 mm had significantly higher Emax (148.04 kPa) and Emean (118.32 kPa) (P=0.005) than smaller lesions. We found no statistically significant correlations between elasticity parameters and histologic type and grade or molecular subtypes, although tumors with HER2 overexpression regardless whether they expressed hormone receptors (luminal B HER2+ and HER2 phenotypes) and triple-negative tumors had lower Emax and Emean than the others. We assessed the B-mode ultrasound findings of the lesions with some of the Emax or Emean values less than or equal to 80 kPa; only four of these had ultrasound findings suggestive of a benign lesion (two with luminal A phenotype and two with HER2 phenotype)., Conclusions: We were unable to demonstrate statistically significant differences among the subtypes of invasive tumors, although there appears to be a trend toward lower Emax and Emean in the aggressive phenotypes., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Benign breast disease increases the risk of breast cancer. This association has scarcely been evaluated in the context of breast cancer screening programs although it is a prevalent finding in mammography screening. We assessed the association of distinct categories of benign breast disease and subsequent risk of breast cancer, as well as the influence of a family history of breast cancer. A retrospective cohort study was conducted in 545,171 women aged 50-69 years biennially screened for breast cancer in Spain. The median of follow-up was 6.1 years. The age-adjusted rate ratio (RR) of breast cancer for women with benign breast disease, histologically classified into nonproliferative and proliferative disease with and without atypia, compared with women without benign breast disease was estimated by Poisson regression analysis. A stratified analysis by family history of breast cancer was performed in a subsample. All tests were two-sided. The age-adjusted RR of breast cancer after diagnosis of benign breast disease was 2.51 (95 % CI: 2.14-2.93) compared with women without benign breast disease. The risk was higher in women with proliferative disease with atypia (RR = 4.56, 95 % CI: 2.06-10.07) followed by those with proliferative disease without atypia (RR = 3.58; 95 % CI = 2.61-4.91). Women with nonproliferative disease and without a family history of breast cancer remained also at increased risk of cancer (OR = 2.23, 95 % CI: 1.86-2.68). An increased risk of breast cancer was observed among screening participants with proliferative or nonproliferative benign breast disease, regardless of a family history of breast cancer. This information may be useful to explore risk-based screening strategies.

Introduction: Interval cancers are tumors arising after a negative screening episode and before the next screening invitation. They can be classified into true interval cancers, false-negatives, minimal-sign cancers, and occult tumors based on mammographic findings in screening and diagnostic mammograms. This study aimed to describe tumor-related characteristics and the association of breast density and tumor phenotype within four interval cancer categories., Methods: We included 2,245 invasive tumors (1,297 screening-detected and 948 interval cancers) diagnosed from 2000 to 2009 among 645,764 women aged 45 to 69 who underwent biennial screening in Spain. Interval cancers were classified by a semi-informed retrospective review into true interval cancers (n = 455), false-negatives (n = 224), minimal-sign (n = 166), and occult tumors (n = 103). Breast density was evaluated using Boyd's scale and was conflated into: <25%; 25 to 50%; 50 to 75%; >75%. Tumor-related information was obtained from cancer registries and clinical records. Tumor phenotype was defined as follows: luminal A: ER+/HER2- or PR+/HER2-; luminal B: ER+/HER2+ or PR+/HER2+; HER2: ER-/PR-/HER2+; triple-negative: ER-/PR-/HER2-. The association of tumor phenotype and breast density was assessed using a multinomial logistic regression model. Adjusted odds ratios (OR) and 95% confidence intervals (95% CI) were calculated. All statistical tests were two-sided., Results: Forty-eight percent of interval cancers were true interval cancers and 23.6% false-negatives. True interval cancers were associated with HER2 and triple-negative phenotypes (OR = 1.91 (95% CI:1.22-2.96), OR = 2.07 (95% CI:1.42-3.01), respectively) and extremely dense breasts (>75%) (OR = 1.67 (95% CI:1.08-2.56)). However, among true interval cancers a higher proportion of triple-negative tumors was observed in predominantly fatty breasts (<25%) than in denser breasts (28.7%, 21.4%, 11.3% and 14.3%, respectively; <0.001). False-negatives and occult tumors had similar phenotypic characteristics to screening-detected cancers, extreme breast density being strongly associated with occult tumors (OR = 6.23 (95% CI:2.65-14.66)). Minimal-sign cancers were biologically close to true interval cancers but showed no association with breast density., Conclusions: Our findings revealed that both the distribution of tumor phenotype and breast density play specific and independent roles in each category of interval cancer. Further research is needed to understand the biological basis of the overrepresentation of triple-negative phenotype among predominantly fatty breasts in true interval cancers.

Background: Breast cancer incidence has decreased in the last decade, while the incidence of ductal carcinoma in situ (DCIS) has increased substantially in the western world. The phenomenon has been attributed to the widespread adaption of screening mammography. The aim of the study was to evaluate the temporal trends in the rates of screen detected invasive cancers and DCIS, and to compare the observed trends with respect to hormone replacement therapy (HRT) use along the same study period., Methods: Retrospective cohort study of 1,564,080 women aged 45-69 years who underwent 4,705,681 screening mammograms from 1992 to 2006. Age-adjusted rates of screen detected invasive cancer, DCIS, and HRT use were calculated for first and subsequent screenings. Poisson regression was used to evaluate the existence of a change-point in trend, and to estimate the adjusted trends in screen detected invasive breast cancer and DCIS over the study period., Results: The rates of screen detected invasive cancer per 100.000 screened women were 394.0 at first screening, and 229.9 at subsequent screen. The rates of screen detected DCIS per 100.000 screened women were 66.8 at first screen and 43.9 at subsequent screens. No evidence of a change point in trend in the rates of DCIS and invasive cancers over the study period were found. Screen detected DCIS increased at a steady 2.5% per year (95% CI: 1.3; 3.8), while invasive cancers were stable., Conclusion: Despite the observed decrease in breast cancer incidence in the population, the rates of screen detected invasive cancer remained stable during the study period. The proportion of DCIS among screen detected breast malignancies increased from 13% to 17% throughout the study period. The rates of screen detected invasive cancer and DCIS were independent of the decreasing trend in HRT use observed among screened women after 2002.

Background: The aim of this study was to evaluate the calibration and discriminatory power of three predictive models of breast cancer risk., Methods: We included 13,760 women who were first-time participants in the Sabadell-Cerdanyola Breast Cancer Screening Program, in Catalonia, Spain. Projections of risk were obtained at three and five years for invasive cancer using the Gail, Chen and Barlow models. Incidence and mortality data were obtained from the Catalan registries. The calibration and discrimination of the models were assessed using the Hosmer-Lemeshow C statistic, the area under the receiver operating characteristic curve (AUC) and the Harrell's C statistic., Results: The Gail and Chen models showed good calibration while the Barlow model overestimated the number of cases: the ratio between estimated and observed values at 5 years ranged from 0.86 to 1.55 for the first two models and from 1.82 to 3.44 for the Barlow model. The 5-year projection for the Chen and Barlow models had the highest discrimination, with an AUC around 0.58. The Harrell's C statistic showed very similar values in the 5-year projection for each of the models. Although they passed the calibration test, the Gail and Chen models overestimated the number of cases in some breast density categories., Conclusions: These models cannot be used as a measure of individual risk in early detection programs to customize screening strategies. The inclusion of longitudinal measures of breast density or other risk factors in joint models of survival and longitudinal data may be a step towards personalized early detection of BC.

Background: 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., Methods: 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., Results: 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)., Conclusion: 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.

The frequency of interval cancers (IC) can be an indicator inversely related to the quality of a breast screening programme. The objectives were to estimate the frequency of IC, to classify IC by posterior radiological review, and to describe the prognostic factors of these IC. The setting was the Sabadell-Cerdanyola Breast Cancer Screening Programme, in Northeast Spain. We developed a population-based study of the IC occurring in the first three rounds (1995-2001). The indicators used were the incidence rate of invasive IC per 10 000 women screened and the proportional incidence, stratified by age group, type of screening and the round, and the time elapsed since the last screening mammogram. A radiological informed consensus review was used to classify the IC. No specific pattern of incidence rates was evident with respect to age, type of screening, or round, although screening was generally more sensitive in women aged 60-69 years. The proportional incidence for the period 0-11 months was always under 30%. Twenty-one percent of 38 IC evaluated (95% CI: 8.0-34.0) were attributed to errors in the screening process (false negatives). No major differences in the prognostic factors of the 57 IC were identified on examining the radiological type or the time since the last screening mammogram. We observed a high frequency of IC from 12 months after screening. It is necessary to reach a consensus regarding the definition and the analysis of IC and to establish mechanisms that would allow all the malignant tumours diagnosed in the target population to be identified.

The purpose of the study was to compare two methods used to analyse HER-2 gene amplification (fluorescence in situ hybridisation (FISH) and chromogenic in situ hybridisation (CISH)), and determine the accuracy of the antibodies CB11 and HercepTest for immunohistochemical detection of HER-2 overexpression from archival breast cancer tissue. Additionally, interobserver variability in the interpretation of CISH and immunohistochemical tests was measured. Two hundred cases of invasive breast carcinoma diagnosed between 2000 and 2003 were selected. Immunohistochemistry (IHC) was performed with HercepTest and CB11, and gene amplification was determined by FISH (PathVision, Vysis) and CISH (Zymed) using tissue macroarrays. An excellent concordance (94.8%) was found between CISH and FISH. Considering FISH as gold standard, sensitivity of CISH was 97.5% and specificity 94%. Overall interobserver agreement of CISH was 97.5% and of IHC 84%. Both antibodies showed a sensitivity of 95.2% and a specificity of 70.7% (CB11) and 81.2% (HercepTest). Our results show that CISH is a highly accurate, reproducible and practical technique to determine HER-2 gene amplification. CB11 and HercepTest are good screening methods with a high sensitivity. The performance of tissue macroarrays to test HER-2 status by IHC, FISH and CISH has demonstrated to be an available and effective method to study large series of tumours.

Objectives: To analyse and compare the prognostic factors of breast cancer in the target population of our community-screening programme as a function of the method of detection and to analyse the differences in the prognostic factors as a function of the patient's age and the screening episode., Setting: A Breast Cancer-Screening Programme (BCSP) in Northeast Spain., Methods: Observational study of all primary malignant breast lesions diagnosed in a woman between 50 and 69 years of age between 18 October 1995 and 31 December 2002. The 16 centres that women from the target population might have attended were contacted., Results: A total of 225 (37.2%) of the lesions included were diagnosed through the BCSP, 59 (9.7%) interval cancers were detected, and 321 (53.1%) were detected through other circuits. Node involvement was significantly lower in the lesions detected at screening (32%) in comparison to the interval cancers (41.8%) and those detected through other circuits (47.5%). A significantly larger percentage of the interval tumours (28.6%) and the lesions diagnosed outside the BCSP (22.1%) scored >5.4 on the Nottingham Prognostic Index (NPI) than those diagnosed within the programme (10.9%). The relation between the NPI and the detection method was only statistically significant in the 65-69-year-old age group. The NPI score of the tumours detected by the BCSP showed a statistically significant association with age., Conclusion: This analysis has shown notable differences in some prognostic factors for breast cancer according to the method of detection. Association between age and the a priori prognosis of the malignant lesions arises.

The main objectives were to describe the measures taken by women to detect breast disease prior to invitation to participate in a screening programme for breast cancer, and to identify factors related to non-participation in this programme. A cross-sectional study was designed at the Breast Cancer Early Detection Program of Sabadell-Cerdanyola (BCEDP), using data collected in interviews conducted face to face or over the telephone with 13 760 women participating in the programme and 280 non-participants. A total of 74.2% of the participants versus 70.4% of the non-participants reported having taken measures to detect breast disease, and 71.7% of the participants had undergone mammography versus 69.6% of the non-participants. Of the 10 057 women who had had mammograms, 58% had done so less than 2 years previously. Factors found to be associated to non-participation in the multivariate analysis were: higher level of education, higher occupational skills or working at home, self- or gynaecological examination of breasts, and having received hormone replacement therapy. Higher age group was the only factor that increased the probability of not having undergone mammography previously. Despite the high prevalence of prior measures to detect breast cancer and the similar prevalence between participating and non-participating women, this behaviour is much less prevalent in the group of women 60 years of age or older.