Interaction of sedentary behaviour and educational level in breast cancer risk.

OBJECTIVE: This cross-sectional study aims to analyse the relationship between sedentary behaviour and breast cancer (BC) risk from a social perspective. METHODS: Women aged 45-70 who participated in the Valencia Region Breast Cancer Screening Programme (2018-2019) were included, with a total of 121,359 women analysed, including 506 with cancer and 120,853 without cancer. The response variable was BC (screen-detected) and the main explanatory variable was sedentary behaviour (≤2 / >2-≤3 / >3-≤5 / >5 hours/day, h/d). Nested logistic regression models (M) were estimated: M1: sedentary behaviour adjusted for age and family history of BC; M2: M1 + hormonal/reproductive variables (menopausal status, number of pregnancies, hormone replacement therapy; in addition, months of breastfeeding was added for a subsample of women with one or more live births); M3: M2 + lifestyle variables (body mass index, smoking habits); M4: M3 + socioeconomic variables (educational level, occupation); Final model: M4 + gender variables (childcare responsibilities, family size). Interaction between sedentary behaviour and educational level was analysed in the Final model. Moreover, for the whole sample, postmenopausal women and HR+ BC, the Final model was stratified by educational level. RESULTS: Sedentary behaviour was associated with an increased risk of BC with a nearly statistically significant effect in the Final model (>2-≤3 h/d: OR = 1.22 (0.93-1.61); >3-≤5 h/d: OR = 1.14 (0.86-1.52); >5: OR = 1.19 (0.89-1.60)). For women with a low educational level, sitting more than 2 h/d was associated with an increased risk of BC in the whole sample (>2-≤3 h/d OR = 1.93 (1.19-3.21); in postmenopausal women (>2-≤3 h/d, OR = 2.12 (1.18-2.96), >5h/d OR = 1.75 (1.01-3.11)) and in HR+ BC (>2-≤3h/d, OR = 2.15 (1.22-3.99)). Similar results were observed for women with one or more live births. Conclusions Sitting >2 h/d is associated with BC risk in women with low educational level, especially in postmenopausal women and those with live births.

Impact of different age ranges on the benefits and harms of the breast cancer screening programme by the EU-TOPIA tool.

BACKGROUND: The recommendation for the implementation of mammography screening in women aged 45-49 and 70-74 is conditional with moderate certainty of the evidence. The aim of this study is to simulate the long-term outcomes (2020-50) of using different age range scenarios in the breast cancer screening programme of the Valencia Region (Spain), considering different programme participation rates. METHODS: Three age range scenarios (S) were simulated with the EU-TOPIA tool, considering a biennial screening interval: S1, 45-69 years old (y); S2, 50-69 y and S3, 45-74 y. Simulations were performed for four participation rates: A = current participation (72.7%), B = +5%, C = +10% and D = +20%. Considered benefits: number (N°) of in situ and invasive breast cancers (BC) (screen vs. clinically detected), N° of BC deaths and % BC mortality reduction. Considered harms: N° of false positives (FP) and % overdiagnosis. RESULTS: The results showed that BC mortality decreased in all scenarios, being higher in S3A (32.2%) than S1A (30.6%) and S2A (27.9%). Harms decreased in S2A vs. S1A (N° FP: 236 vs. 423, overdiagnosis: 4.9% vs. 5.0%) but also benefits (BC mortality reduction: 27.9% vs. 30.6%, N° screen-detected invasive BC 15/28 vs. 18/25). In S3A vs. S1A, an increase in benefits was observed (BC mortality reduction: 32.2% vs. 30.6%), N° screen-detected in situ B: 5/2 vs. 4/3), but also in harms (N° FP: 460 vs. 423, overdiagnosis: 5.8% vs. 5.0%). Similar trends were observed with increased participation. CONCLUSIONS: As the age range increases, so does not only the reduction in BC mortality, but also the probability of FP and overdiagnosis.

Interval Cancer in Population-Based Colorectal Screening Programmes: Incidence and Characteristics of Tumours.

The objective of this study is to evaluate interval cancer (IC) in colorectal cancer (CRC) screening, which is CRC diagnosed in an individual after having received a negative faecal occult blood test and before the next invitation to participate in screening. A follow-up study was conducted on a cohort of participants in the first three screening rounds of four colorectal cancer screening programmes in Spain, n = 664,993. A total of 321 ICs and 2120 screen-detected cancers (SCs) were found. The IC and SC rates were calculated for each guaiac (gFOBT) or immunochemical (FIT) test. A Cox regression model was used to estimate the hazard ratios (HR) of IC risk factors. A nested case-control study was carried out to compare IC and SC tumour characteristics. The IC rate was 1.16‱ with the gFOBT and 0.35‱ with the FIT. Men and people aged 60-69 showed an increased probability of IC (HR = 1.81 and HR = 1.95, respectively). There was a decreased probability of IC in individuals who regularly participated in screening, HR = 0.62 (0.47-0.82). IC risk gradually rose as the amount of Hb detected in the FIT increased. IC tumours were in more advanced stages and of a larger size than SC tumours, and they were mostly located in the cecum. These results may play a key role in future strategies for screening programmes, reducing IC incidence.

Optimal cut-off value for detecting colorectal cancer with fecal immunochemical tests according to age and sex.

In the fecal immunological test, a suitable cut-off value may be selected to classify results as either positive or negative. Our aim is to estimate the optimal cut-off value for detecting colorectal cancer in different age and sex groups. This is a multicentric retrospective cohort study of participants in CRC screening programs with FIT between 2006 and 2012. A total of 545,505 participations were analyzed. Cancers diagnosed outside of the program were identified after a negative test result (IC_test) up until 2014. The Wilcoxon test was used to compare fecal hemoglobin levels. ROC curves were used to identify the optimal cut-off value for each age and sex group. Screening program results were estimated for different cut-off values. The results show that the Hb concentration was higher in colorectal cancer (average = 179.6µg/g) vs. false positives (average = 55.2µg/g), in IC_test (average = 3.1µg/g) vs. true negatives (average = 0µg/g), and in men (average = 166.2µg/g) vs. women (average = 140.2µg/g) with colorectal cancer. The optimal cut-off values for women were 18.3µg/g (50-59y) and 14.6µg/g (60-69y), and 16.8µg/g (50-59y) and 19.9µg/g (60-69y) for men. Using different cut-off values for each age and sex group lead to a decrease in the IC_test rate compared to the 20µg/g cut-off value (from 0.40‰ to 0.37‰) and an increase in the false positive rate (from 6.45% to 6.99%). Moreover, test sensitivity improved (90.7%), especially in men and women aged 50-59y (89.4%; 90%) and women aged 60-69y (90.2%). In conclusion, the optimal cut-off value varies for different sex and age groups and the use of an optimal cut-off value for each group improves sensitivity and leads to a small decrease in IC_tests, but also to a larger increase in false positives.

Tumour characteristics and survivorship in a cohort of breast cancer: the MCC-Spain study.

PURPOSE: The objective of this study is to analyse the relative survival with breast cancer in women diagnosed after new treatments were generalised and to ascertain the current effect that tumour characteristics such as grade, stage or subtype have on survival as well as the new AJCC-pathological prognostic score. METHODS: The breast cancer MCC-Spain follow-up study is a prospective cohort study of 1685 incident breast cancer cases. Women between 20 and 85 years old were recruited between the years 2008 and 2013 in 18 hospitals located in 10 Spanish provinces and they have been followed until 2017/2018. Relative survival was estimated after 3, 5 and 8 years of follow-up using Ederer II method. In addition, Weibull regression adjusted by age, hospital, grade and stage was used to investigate prognosis factors. RESULTS: Among components of TNM staging system, tumour size greater than 50 mm (i.e. T3 or T4) more than doubled the risk of dying, while N3 nodal involvement and presence of metastasis had a huge effect on mortality. The AJCC pathological prognostic score strongly correlated with survival; thus, hazard ratios increased as the score rose, being 2.31, 4.00, 4.94, 7.92, 2.26, 14.9 and 58.9 for scores IB, IIA, IIB, IIIA, IIIB, IIIC and IV, respectively. CONCLUSION: Both TNM staging and histological/molecular biomarkers are associated with overall survival in Spanish women with breast cancer; when both are combined in the AJCC pathological prognosis score, the prognostic value improved with risk indices that increased rapidly as the pathological prognosis score increased.

Risk factors for severe complications of colonoscopy in screening programs.

Severe complications (SC) in colonoscopy represent the most important adverse effect of colorectal cancer screening programs (CRCSP). The objective is to evaluate the risk factors for SC in colonoscopy indicated after a positive fecal occult blood test in population-based CRCSP. The SC (n = 161) identified from 48,730 diagnostic colonoscopies performed in a cohort of all the women and men invited from 2000 to 2012 in 6 CRCSP in Spain. A total of 318 controls were selected, matched for age, sex and period when the colonoscopy was performed. Conditional logistic regression models were estimated. The analysis was performed separately in groups: immediate-SC (same day of the colonoscopy); late-SC (between 1 and 30 days after); perforation; and bleeding events. SC occurred in 3.30‰ of colonoscopies. Prior colon disease showed a higher risk of SC (OR = 4.87). Regular antiplatelet treatment conferred a higher risk of overall SC (OR = 2.80) and late-SC (OR = 9.26), as did regular anticoagulant therapy (OR = 3.47, OR = 7.36). A history of pelvic-surgery or abdominal-radiotherapy was a risk factor for overall SC (OR = 5.03), immediate-SC (OR = 8.49), late-SC (OR = 4.65) and perforation (OR = 21.59). A finding of adenoma or cancer also showed a higher risk of overall SC (OR = 8.71), immediate-SC (OR = 12.67), late-SC (OR = 4.08), perforation (OR = 4.69) and bleeding (OR = 17.02). The risk of SC doesn't vary depending on the type of preparation or type of anesthesia. Knowing the clinical history of patients such as regular previous medication and history of surgery or radiotherapy, as well as the severity of the findings during the colonoscopy process could help to focus prevention measures in order to minimize SC in CRCSP.

Complicaciones graves en las colonoscopias de cribado del cáncer colorrectal en la Comunidad Valenciana / Severe complications in colorectal cancer screening colonoscopies in the Valencian Community

OBJETIVO: Identificar y caracterizar las complicaciones graves de las colonoscopias de confirmación diagnóstica del Programa de Prevención de Cáncer Colorrectal de la Comunitat Valenciana (PPCCR-CV). MÉTODO: Estudio observacional retrospectivo (2005-2012). Para identificar las complicaciones se utilizó el sistema de información del PPCCR-CV, las altas hospitalarias del conjunto mínimo básico de datos (CMBD) y la historia clínica. Se estimaron tasas de incidencia acumulada para el total de complicaciones, para inmediatas (mismo día de la colonoscopia) y tardías (1-30 días desde la colonoscopia) por 1.000 colonoscopias. Análisis bivariado con la prueba Chi cuadrado para la aparición de complicación según sexo, edad y tipo de test (guayaco/inmunológico) y para el tiempo de aparición de la complicación (inmediata/tardía) según el tipo de colonoscopia (diagnóstica/terapéutica) y el tipo de complicación (hemorragia/perforación). RESULTADOS: De las 8.831 colonoscopias del estudio se detectaron 23 complicaciones graves de las cuales 13 fueron perforaciones (56,5%) y 10 hemorragias (43,5%) y ningún síndrome vagal grave, peritonitis o fallecimiento. La tasa de incidencia acumulada fue del 2,60‰, para el test de guayaco del 2,85‰ y del 2,56‰ para el inmunológico. La tasa de incidencia fue mayor en hombres (2,93‰) que en mujeres (2,16‰) y en grupos de mayor edad (3,02‰ vs. 1,98‰). El 61% (n = 14) de las complicaciones fueron inmediatas. CONCLUSIONES: Las tasas de complicaciones de las colonoscopias de cribado graves son un indicador de calidad de los programas poblacionales de cribado de cáncer colorrectal y requieren una investigación exhaustiva para mantener el balance adecuado de beneficios y efectos adversos de estos programas

OBJECTIVE: To identify and characterise the severe complications of diagnostic confirmation colonoscopies carried out as part of the Colorectal Cancer Screening Program of the Valencian Community (CCSP-VC). METHOD: A retrospective observational study from 2005 to 2012. To identify complications, the CCSP-VC information system was used, as well as Spanish Minimum Basic Data Set hospital discharge summaries and medical records. Cumulative incidence rates were estimated for all complications, immediate complications (occurring the same day as the colonoscopy) and delayed complications (occurring 1-30 days after the colonoscopy) for the 1,000 colonoscopies performed. A bivariate analysis using the Chi-square test was performed for the onset of complications, according to gender, age and type of test (guaiac/immunological), as well as for the complication onset time (immediate/delayed) based on the type of colonoscopy (diagnostic/therapeutic) and type of complication (haemorrhage/perforation). RESULTS: Of the total 8,831 screening colonoscopies performed, 23 severe complications were observed, 13 of which were perforations (56.5%) and 10 haemorrhages (43.5%). No serious vagal syndrome, peritonitis or deaths were recorded. The cumulative incidence rate was 2.60‰; 2.85‰ for the guaiac test and 2.56‰ for the immunological test. The incidence rate was higher in men (2.93‰) than in women (2.16‰), as well as in older groups (3.02‰ versus 1.98‰). Of the total complications, 61% (n=14) were immediate. CONCLUSIONS: The severe complication rates of screening colonoscopies are a quality indicator for population-based colorectal cancer screening programs that require extensive research in order to maintain the appropriate risk/benefit ratio of such programs

Severe complications in colorectal cancer screening colonoscopies in the Valencian Community. / Complicaciones graves en las colonoscopias de cribado del cáncer colorrectal en la Comunidad Valenciana.

OBJECTIVE: To identify and characterise the severe complications of diagnostic confirmation colonoscopies carried out as part of the Colorectal Cancer Screening Program of the Valencian Community (CCSP-VC). METHOD: A retrospective observational study from 2005 to 2012. To identify complications, the CCSP-VC information system was used, as well as Spanish Minimum Basic Data Set hospital discharge summaries and medical records. Cumulative incidence rates were estimated for all complications, immediate complications (occurring the same day as the colonoscopy) and delayed complications (occurring 1-30 days after the colonoscopy) for the 1,000 colonoscopies performed. A bivariate analysis using the Chi-square test was performed for the onset of complications, according to gender, age and type of test (guaiac/immunological), as well as for the complication onset time (immediate/delayed) based on the type of colonoscopy (diagnostic/therapeutic) and type of complication (haemorrhage/perforation). RESULTS: Of the total 8,831 screening colonoscopies performed, 23 severe complications were observed, 13 of which were perforations (56.5%) and 10 haemorrhages (43.5%). No serious vagal syndrome, peritonitis or deaths were recorded. The cumulative incidence rate was 2.60‰; 2.85‰ for the guaiac test and 2.56‰ for the immunological test. The incidence rate was higher in men (2.93‰) than in women (2.16‰), as well as in older groups (3.02‰ versus 1.98‰). Of the total complications, 61% (n=14) were immediate. CONCLUSIONS: The severe complication rates of screening colonoscopies are a quality indicator for population-based colorectal cancer screening programs that require extensive research in order to maintain the appropriate risk/benefit ratio of such programs.

Factors influencing participation in colorectal cancer screening programs in Spain.

To analyze the sociodemographic and organizational factors influencing participation in population-based colorectal cancer screening programs (CRCSP) in Spain, a retrospective study was conducted in a cohort of people invited to participate in the first 3 screening rounds of 6 CRCSP from 2000 to 2012. Mixed logistic regression models were used to analyze the relationship between sociodemographic and organizational factors, such as the type of fecal occult blood test (FOBT) used and the FOBT delivery type. The analysis was performed separately in groups (Initial screening-first invitation, Subsequent invitation for previous never-responders, Subsequent invitation-regular, Subsequent invitation-irregular intervals). The results showed that, in the Initial screening-first invitation group, participation was higher in women than in men in all age groups (OR 1.05 in persons aged 50-59years and OR 1.12 in those aged 60-69years). Participation was also higher when no action was required to receive the FOBT kit, independently of the type of screening (Initial screening-first invitation [OR 2.24], Subsequent invitation for previous never-responders [OR 2.14], Subsequent invitation-regular [OR 2.03], Subsequent invitation-irregular intervals [OR 9.38]) and when quantitative rather than qualitative immunological FOBT (FIT) was offered (Initial screening-first invitation [OR 0.70], Subsequent invitation for previous never-responders [OR 0.12], Subsequent invitation-regular [OR 0.20]) or guaiac testing (Initial screening-first invitation [OR 0.81], Subsequent invitation for previous never-responders [OR 0.88], Subsequent invitation-regular [OR 0.73]). In conclusion, the results of this study show that screening participation could be enhanced by inclusion of the FOBT kit with the screening invitation and the use of the quantitative FIT.

Mammographic and clinical characteristics of different phenotypes of screen-detected and interval breast cancers in a nationwide screening program.

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.

Impact of risk factors on different interval cancer subtypes in a population-based breast cancer screening programme.

BACKGROUND: Interval cancers are primary breast cancers diagnosed in women after a negative screening test and before the next screening invitation. Our aim was to evaluate risk factors for interval cancer and their subtypes and to compare the risk factors identified with those associated with incident screen-detected cancers. METHODS: We analyzed data from 645,764 women participating in the Spanish breast cancer screening program from 2000-2006 and followed-up until 2009. A total of 5,309 screen-detected and 1,653 interval cancers were diagnosed. Among the latter, 1,012 could be classified on the basis of findings in screening and diagnostic mammograms, consisting of 489 true interval cancers (48.2%), 235 false-negatives (23.2%), 172 minimal-signs (17.2%) and 114 occult tumors (11.3%). Information on the screening protocol and women's characteristics were obtained from the screening program registry. Cause-specific Cox regression models were used to estimate the hazard ratios (HR) of risks factors for interval cancer and incident screen-detected cancer. A multinomial regression model, using screen-detected tumors as a reference group, was used to assess the effect of breast density and other factors on the occurrence of interval cancer subtypes. RESULTS: A previous false-positive was the main risk factor for interval cancer (HR = 2.71, 95%CI: 2.28-3.23); this risk was higher for false-negatives (HR = 8.79, 95%CI: 6.24-12.40) than for true interval cancer (HR = 2.26, 95%CI: 1.59-3.21). A family history of breast cancer was associated with true intervals (HR = 2.11, 95%CI: 1.60-2.78), previous benign biopsy with a false-negatives (HR = 1.83, 95%CI: 1.23-2.71). High breast density was mainly associated with occult tumors (RRR = 4.92, 95%CI: 2.58-9.38), followed by true intervals (RRR = 1.67, 95%CI: 1.18-2.36) and false-negatives (RRR = 1.58, 95%CI: 1.00-2.49). CONCLUSION: The role of women's characteristics differs among interval cancer subtypes. This information could be useful to improve effectiveness of breast cancer screening programmes and to better classify subgroups of women with different risks of developing cancer.

Participation and detection rates by age and sex for colonoscopy versus fecal immunochemical testing in colorectal cancer screening.

PURPOSE: To compare two strategies for colorectal cancer screening: one-time colonoscopy versus fecal immunochemical testing (FIT) (and colonoscopy for positive) every 2 years, in order to determine which strategy provides the highest participation and detection rates in groups of sex and age. METHODS: This analysis was performed with data from the first screening round within the COLONPREV study, a population-based, multicenter, nationwide trial carried out in Spain. Several logistic regression models were applied to identify the influence of the screening test on participation rates and detection of proximal and distal neoplasms, as well to identify the influence of age and sex: women aged 50-59 years, women aged 60-69 years, men aged 50-59 years, and men aged 60-69 years. RESULTS: Participation was higher in women than in men, especially among women aged 50-59 years (25.91 % for colonoscopy and 35.81 % for FIT). Crossover from colonoscopy to FIT was higher among women than men, especially among those aged 60-69 years (30.37 %). In general, detection of any neoplasm and advanced adenoma was higher with colonoscopy than with FIT, but no significant differences were found between the two strategies for colorectal cancer detection. Detection of advanced adenoma in both arms was lower in women [specifically in women aged 50-59 years (OR 0.31; 95 % CI 0.25-0.38) than in men aged 60-69 years]. Women aged 50-59 years in the colonoscopy arm had a higher probability of detection of advanced adenoma (OR 4.49; 95 % CI 3.18-6.35), as well as of detection of neoplasms in proximal and distal locations (proximal OR 19.34; 95 % CI 12.07-31.00; distal OR 11.04; 95 % CI 8.13-15.01) than women of the same age in the FIT arm. These differences were also observed in the remaining groups but to a lesser extent. CONCLUSION: Women were more likely to participate in a FIT-based strategy, especially those aged 50-59 years. The likelihood of detection of any neoplasm was higher in the colonoscopy arm for all the population groups studied, especially in women aged 50-59 years. Distinct population groups should be informed of the benefits of each screening strategy so that they may take informed decisions.

Tumor phenotype and breast density in distinct categories of interval cancer: results of population-based mammography screening in Spain.

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.

Clinical and radiological features of breast tumors according to history of false-positive results in mammography screening.

BACKGROUND: Women with a false-positive result after a screening mammogram have an increased risk of cancer detection in subsequent participations, especially after assessments involving cytology or biopsy. We aimed to compare women's personal characteristics, tumoral features and the radiological appearance of cancers with and without a previous false-positive result generated by additional imaging or invasive procedures. METHODS: From 1996 to 2007, 111,098 women aged 45-69 years participated in four population-based breast cancer screening programs in Spain, and 1281 cancers were detected. We included all cancers detected in subsequent screenings (n=703) and explored the occurrence of previous false-positive results. We identified false-positives requiring additional imaging or invasive procedures. Differences on tumoral features (invasiveness, tumor size, and lymph node status) and radiological appearance were assessed by Chi-square test, and agreement between the location of cancer and prior suspicious by Cohen's kappa coefficient. A multivariate analysis was preformed to evaluate the effect of previous screening results and age on the odds of presenting an in situ carcinoma. RESULTS: Among the 703 cancers detected in subsequent screenings, 148 women (21.1%) had a previous false-positive result. Of these, 105 were by additional imaging and 43 by invasive procedures. Women with prior false-positive result requiring invasive assessment, compared to women with negative tests, and women with prior false-positive requiring additional imaging, had a higher proportion of in situ carcinomas (31.7%, 15.3%, 12.9%, respectively; p=0.014) and microcalcifications (37.2%, 20.2%, 9.5%, respectively; p=0.003). The proportion of in situ carcinomas was even higher in women over 60 years (39.2%, 12.5%, 13.0%, respectively; p=0.001). Ipsilateral cancer was observed in 65.7% of cases with prior cytology or biopsy (k=0.479; 95%CI: 0.330-0.794). CONCLUSION: A large number of in situ malignancies and calcification patterns were found among women with prior false-positive result in mammography screening requiring cytology or biopsies, suggesting progression from a previously benign lesion.

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

OBJECTIVES: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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 start age of breast cancer screening mammography on the risk of false-positive results.

OBJECTIVE: To estimate the false-positive (FP) risk according to the start age of mammography screening (45-46 or 50-51 years). METHOD: Data from eight regions of the Spanish breast cancer screening programme from 1990 to 2006 were included (1,565,364 women). Discrete time-hazard models were used to ascertain the effect of age and time-related, programme-related and personal variables on FP leading to any further procedure and to invasive procedures (FPI). In a subset we estimated the differential FP risk of starting screening at 45-46 years (175,656 women) or 50-51 (251,275). RESULTS: A start age of 45-46 versus 50-51 years increased both FP (OR=1.20; 95%CI: 1.13-1.26) and FPI risks (OR=1.43 (95%CI: 1.18-1.73).Other factors increasing FP risk were premenopausal status (FP OR=1.26; 95%CI: 1.23-1.29 and FPI OR=1.22; 95%CI: 1.13-1.31), prior invasive procedures (FP OR=1.52; 95%CI: 1.47-1.57 and FPI (OR=2.08; 95%CI: 1.89-2.28) and family history (FP OR=1.16; 95%CI: 1.12-1.20 and FPI OR=1.26; 95%CI: 1.13-1.41). FP risk was increased by double reading (OR=1.36; 95%CI: 1.23-1.51) and FPI risk by double views (OR=1.34; 95%CI: 1.18-1.52). Both the cumulative FP and FPI risks were higher in women commencing screening at 45-46 years versus 50-51 years (33.30% versus 20.39% and 2.68% versus 1.76%). CONCLUSIONS: Starting screening earlier increases the cumulative risk of FP and FPI.

Reduction in false-positive results after introduction of digital mammography: analysis from four population-based breast cancer screening programs in Spain.

PURPOSE: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Impact of a mammography screening programme on the breast cancer population of the Region of Valencia (Spain).

OBJECTIVE: Randomised clinical trials with a control arm of non-screened patients are nowadays ethically impossible. The aim of this study was to establish the impact of mammography screening on a non-selected population. PATIENTS AND METHODS: Between January 1993 and December 2002, 3662 patients were included, 2313 in the screened group and 1349 in the unscreened group. RESULTS: 55.3% of the screened patients were diagnosed in stage I vs. 26.1% in the non-screened group. The proportion of stage III-IV was 4.6% and 19.8% for the screened and unscreened groups respectively (p<0.001). 48.8% in the screening group were submitted to mastectomy vs. 66.4% of the unscreened patients (p<0.001). Overall survival was superior for the prevalent cases in the screening group, with a relative risk of 0.49, and was not significant for the incident cases. CONCLUSIONS: Diagnosis of breast cancer in the mammography screening programme of the Region of Valencia significantly increases conservative surgery rates and suggests an improvement in survival in prevalent cases. The increased rate of early stages in these patients could be the main reason of this benefit.