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.

Severe Acute Respiratory Syndrome Coronavirus 2 Adaptive Immunity in Nursing Home Residents Following a Third Dose of the Comirnaty Coronavirus Disease 2019 Vaccine.

A third Comirnaty vaccine dose increased severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) receptor-binding domain antibody levels (median, 93-fold) and neutralizing antibody titers against Wuhan-Hu-1 (median, 57-fold), Beta (me 22-fold), Delta, (median, 43-fold), and Omicron (median, 8-fold) variants, but had less impact on S-reactive T-cell immunity in nursing home residents.

Differences in breast cancer-risk factors between screen-detected and non-screen-detected cases (MCC-Spain study).

PURPOSE: The variation in breast cancer (BC)-risk factor associations between screen-detected (SD) and non-screen-detected (NSD) tumors has been poorly studied, despite the interest of this aspect in risk assessment and prevention. This study analyzes the differences in breast cancer-risk factor associations according to detection method and tumor phenotype in Spanish women aged between 50 and 69. METHODS: We examined 900 BC cases and 896 controls aged between 50 and 69, recruited in the multicase-control MCC-Spain study. With regard to the cases, 460 were detected by screening mammography, whereas 144 were diagnosed by other means. By tumor phenotype, 591 were HR+, 153 were HER2+, and 58 were TN. Lifestyle, reproductive factors, family history of BC, and tumor characteristics were analyzed. Logistic regression models were used to compare cases vs. controls and SD vs. NSD cases. Multinomial regression models (controls used as a reference) were adjusted for case analysis according to phenotype and detection method. RESULTS: TN was associated with a lower risk of SD BC (OR 0.30 IC 0.10-0.89), as were intermediate (OR 0.18 IC 0.07-0.44) and advanced stages at diagnosis (OR 0.11 IC 0.03-0.34). Nulliparity in postmenopausal women and age at menopause were related to an increased risk of SD BC (OR 1.60 IC 1.08-2.36; OR 1.48 IC 1.09-2.00, respectively). Nulliparity in postmenopausal women was associated with a higher risk of HR+ (OR 1.66 IC 1.15-2.40). Age at menopause was related to a greater risk of HR+ (OR 1.60 IC 1.22-2.11) and HER2+ (OR 1.59 IC 1.03-2.45) tumors. CONCLUSION: Reproductive risk factors are associated with SD BC, as are HR+ tumors. Differences in BC-risk factor associations according to detection method may be related to prevailing phenotypes among categories.

SARS-CoV-2 Delta-variant breakthrough infections in nursing home residents at midterm after Comirnaty® COVID-19 vaccination.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Delta variant breakthrough infections in nursing home residents following vaccination with Comirnaty® COVID-19 vaccine were characterized. In total, 201 participants (median age, 87 years; range, 64-100; 133 female) from two nursing homes in the Valencian community (Spain) were included. SARS-CoV-2-Spike (S) antibody responses were determined by a lateral flow immunocromatography (LFIC) assay and by quantitative electrochemiluminescent assay in LFIC-negative participants. SARS-CoV-2-S-IFNγ T cells were enumerated by flow cytometry in 10 participants. Nasopharyngeal SARS-CoV-2 RNA loads were quantified by real-time polymerase chain reaction assays. Vaccine breakthrough COVID-19 due to the Delta variant occurred in 39 residents (median age, 87 years; range, 69-96; 31 female) at a median of 6.5 months after vaccination (nine requiring hospitalization). Breakthrough infections occurred at a higher rate (p < 0.0001) in residents who had not been previously infected with SARS-CoV-2 (naïve) (33/108; 18%) than in those with prior diagnosis of SARS-CoV-2 infection (experienced) (6/93; 6.4%), and were more likely (p < 0.0001) to develop in residents who tested negative by LFIC (20/49) at 3 months after vaccination as compared to their LFIC-positive counterparts (19/142). Among LFIC-negative residents, a trend towards lower plasma anti-RBD antibody levels was noticed in those developing breakthrough infection (p = 0.16). SARS-CoV-2 RNA loads in nasopharyngeal specimens were lower in SARS-CoV-2-experienced residents (p < 0.001) and in those testing positive by LFIC (p = 0.13). The frequency of SARS-CoV-2-S-reactive T cells at 3 months was similar in LFIC-negative residents with (n = 7) or without (n = 3) breakthrough infection. Prior history of SARS-CoV-2 infection and detection of S-reactive antibodies by LFIC at 3 months is associated with a lower risk of Delta-variant breakthrough infection in nursing home residents at midterm after Comirnaty® COVID-19 vaccination.

Risk of Colorectal Cancer and Advanced Polyps One Year After Excision of High-Risk Adenomas.

BACKGROUND: Patients with multiple or large adenomas are considered to be high-risk for metachronous colorectal cancer. OBJECTIVE: Evaluate the risks of detecting colorectal cancer, advanced adenoma, and advanced serrated polyps at 1-year surveillance colonoscopy in patients with >5 adenomas or adenomas >20 mm. DESIGN: Descriptive, retrospective, multicentric, cohort study. We calculated the absolute risk of developing colorectal cancer, advanced adenomas, and advanced serrated polyps at the 1-year surveillance colonoscopy. Potential risk factors for advanced neoplasia at follow-up were evaluated with univariable and multivariable logistic regression analyses. SETTINGS: This study included data from a multicenter cohort colorectal cancer screening program, conducted from January 2014 to December 2015, based on fecal immunochemical tests in Spain. PATIENTS: We included 2119 participants with at least 1 adenoma ≥20 mm or ≥5 adenomas of any size. MAIN OUTCOME MEASURES: We calculated the absolute risk of developing colorectal cancer, advanced adenomas, and advanced serrated polyps at the 1-year surveillance colonoscopy. Potential risk factors for advanced neoplasia at follow-up were evaluated with univariable and multivariable logistic regression analyses. RESULTS: At 1 year, participants displayed 6 colorectal cancers (0.3%), 228 advanced adenomas (10.5%), and 58 advanced serrated polyps (2.7%). The adjusted analysis identified 2 factors associated with advanced neoplasia: >5 adenomas (odds ratio 1.53; 95% CI: 1.15-2.03; p = 0.004) and polyps in a proximal location (OR 1.52; 95% CI: 1.15-2.02; p = 0.004). LIMITATIONS: First, the sample size was relatively small compared to other studies with similar aims. Another limitation was the lack of a comparison group, which could have provided more practical results in terms of surveillance recommendations. CONCLUSIONS: The colorectal cancer detection rate at a 1-year colonoscopy surveillance was low among patients classified at high risk of advanced neoplasia. The risk factors for advanced neoplasia were ≥5 adenomas and proximal polyps at baseline. See Video Abstract at http://links.lww.com/DCR/B820 . RIESGO DE CNCER COLORRECTAL Y DE PLIPOS AVANZADOS UN AO DESPUS DE LA RESECCIN DE ADENOMAS DE ALTO RIESGO: ANTECEDENTES:Los pacientes con adenomas múltiples o grandes se consideran de alto riesgo para desarrollar cáncer colorrectal metacrónico.OBJETIVO:Evaluar los riesgos de detectar cáncer colorrectal, adenoma avanzado y pólipos serrados avanzados en la colonoscopia de seguimiento al año, en pacientes con un número mayor o igual a 5 adenomas o adenomas de 20 mm o más.DISEÑO:Estudio descriptivo, retrospectivo, multicéntrico, de cohortes. Calculamos el riesgo absoluto de desarrollar cáncer colorrectal, adenomas avanzados y pólipos serrados avanzados en la colonoscopia de vigilancia al año. Los factores de riesgo potenciales para el desarrollo de una neoplasia avanzada en el seguimiento, fueron evaluados mediante un análisis de regresión logística univariable y multivariable.AJUSTES:Este estudio incluyó datos de un programa de cribado de cáncer colorrectal de cohorte multicéntrico, realizado entre enero de 2014 y diciembre de 2015, con base en pruebas inmunoquímicas de materia fecal, en España.PACIENTES:Incluimos 2119 participantes con al menos un adenoma ≥20 mm o con cinco o más adenomas de cualquier tamaño.PRINCIPALES MEDIDAS DE RESULTADO:Calculamos el riesgo absoluto de desarrollar cáncer colorrectal, adenomas avanzados y pólipos serrados avanzados en la colonoscopia de vigilancia al año. Los potenciales factores de riesgo para desarrollar una neoplasia avanzada en el seguimiento, se evaluaron mediante un análisis de regresión logística univariable y multivariable.RESULTADOS:Al año se encontraron en los pacientes participantes, 6 cánceres colorrectales (0,3%), 228 adenomas avanzados (10,5%) y 58 pólipos serrados avanzados (2,7%). Mediante el análisis ajustado se identificaron dos factores asociados con el desarrollo de neoplasia avanzada: un número igual o mayor a 5 adenomas (razón de probabilidades 1,53; IC del 95%: 1,15-2,03; p = 0,004) y la presencia de pólipos en una ubicación proximal (razón de probabilidades 1,52; IC del 95%: 1,15-2,02; p = 0,004).LIMITACIONES:Primero, el tamaño de la muestra fue relativamente pequeño en comparación con otros estudios con objetivos similares. Otra limitación fue la falta de un grupo comparativo, que podría haber proporcionado resultados más prácticos, en términos de recomendaciones de vigilancia.CONCLUSIÓNES:La tasa de detección de cáncer colorrectal mediante una colonoscopia de vigilancia al año, fue baja entre los pacientes clasificados como de alto riesgo de neoplasia avanzada. Los factores de riesgo para desarrollar una neoplasia avanzada fueron; un número igual o mayor a 5 adenomas y la presencia de pólipos proximales en la colonoscopia inicial de base. Consulte Video Resumen en http://links.lww.com/DCR/B820 . ( Traducción-Eduardo Londoño-Schimmer ).

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.

Implementation of massive sequencing in the genetic diagnosis of hereditary cancer syndromes: diagnostic performance in the Hereditary Cancer Programme of the Valencia Community (FamCan-NGS).

BACKGROUND: Approximately 5 to 10% of all cancers are caused by inherited germline mutations, many of which are associated with different Hereditary Cancer Syndromes (HCS). In the context of the Program of Hereditary Cancer of the Valencia Community, individuals belonging to specific HCS and their families receive genetic counselling and genetic testing according to internationally established guidelines. The current diagnostic approach is based on sequencing a few high-risk genes related to each HCS; however, this method is time-consuming, expensive and does not achieve a confirmatory genetic diagnosis in many cases. This study aims to test the level of improvement offered by a Next Generation Sequencing (NGS) gene-panel compared to the standard approach in a diagnostic reference laboratory setting. METHODS: A multi-gene NGS panel was used to test a total of 91 probands, previously classified as non-informative by analysing the high-risk genes defined in our guidelines. RESULTS: Nineteen deleterious mutations were detected in 16% of patients, some mutations were found in already-tested high-risk genes (BRCA1, BRCA2, MSH2) and others in non-prevalent genes (RAD51D, PALB2, ATM, TP53, MUTYH, BRIP1). CONCLUSIONS: Overall, our findings reclassify several index cases into different HCS, and change the mutational status of 14 cases from non-informative to gene mutation carriers. In conclusion, we highlight the necessity of incorporating validated multi-gene NGS panels into the HCSs diagnostic routine to increase the performance of genetic diagnosis.

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.

Initial results of the oesophageal and gastric cancer registry from the Comunidad Valenciana. / Resultados iniciales del registro de carcinomas esófago-gástricos de la Comunidad Valenciana.

AIMS: To evaluate the initial results of the oesophagogastric cancer registry developed for the Sociedad Valenciana de Cirugía and the Health Department of the Comunidad Valenciana (Spain). METHODS: Fourteen of the 24 public hospitals belonging to the Comunidad Valenciana participated. All patients with diagnosis of oesophageal or gastric carcinomas operated from January 2013 to December 2014 were evaluated. Demographic, clinical and pathological data were analysed. RESULTS: Four hundred and thirty-four patients (120 oesophageal carcinomas and 314 gastric carcinomas) were included. Only two hospitals operated more than 10 patients with oesophageal cancer per year. Transthoracic oesophaguectomy was the most frequent approach (84.2%) in tumours localized within the oesophagus. A total gastrectomy was performed in 50.9% patients with gastroesophageal junction (GOJ) carcinomas. Postoperative 30-day and 90-day mortality were 8% and 11.6% in oesophageal carcinoma and 5.9 and 8.6% in gastric carcinoma. Before surgery, middle oesophagus carcinomas were treated mostly (76,5%) with chemoradiotherapy. On the contrary, lower oesophagus and GOJ carcinomas were treated preferably with chemotherapy alone (45.5 and 53.4%). Any neoadjuvant treatment was administered to 73.6% of gastric cancer patients. Half patients with oesophageal carcinoma or gastric carcinoma received no adjuvant treatment. CONCLUSIONS: This registry revealed that half patients with oesophageal cancer were operated in hospitals with less than 10 cases per year at the Comunidad Valenciana. Also, it detected capacity improvement for some clinical outcomes of oesophageal and gastric carcinomas.

Incidence of advanced neoplasia during surveillance in high- and intermediate-risk groups of the European colorectal cancer screening guidelines.

Background and study aims: The European guidelines for quality assurance in colorectal cancer (CRC) screening have established high-risk (≥ 5 adenomas or an adenoma ≥ 20 mm) and intermediate-risk (3 - 4 adenomas or at least one adenoma 10 - 19 mm in size, or villous histology, or high grade dysplasia) groups with different endoscopic surveillance intervals. The aim of this study was to evaluate the difference in the incidence of advanced neoplasia (advanced adenoma or CRC) between the two risk groups. Patients and methods: This retrospective group study included patients meeting high- or intermediate-risk criteria for adenomas detected in CRC screening programs and the COLONPREV study before European guidelines were adopted in Spain (June 2011) with a 3-year surveillance recommendation according to Spanish guidelines. The primary outcome measure was the incidence of advanced neoplasia in patients undergoing surveillance. The secondary outcome measure was the CRC incidence. We used an adjusted proportional hazards regression model to control confounding variables. Results: The study included 5401 patients (3379 intermediate risk, 2022 high risk). Endoscopic surveillance was performed in 65.5 % of the patients (2.8 ±â€Š1 years). The incidence of advanced neoplasia in the high- and intermediate-risk groups was 16.0 % (59.0 cases/1000 patient-years) and 12.3 % (41.2 cases/1000 patient-years), respectively. The CRC incidence was 0.5 % (1.4 cases/1000 patient-years) and 0.4 % (1 case/1000 patient-years), respectively. The advanced neoplasia and CRC attributable risk to the high risk group was of 3.7 % and 0.1 %, respectively. In the proportional hazards analysis, the risk of advanced neoplasia was greater in the high-risk group (hazard ratio [HR] 1.5, 95 % confidence interval [CI] 1.2 - 1.8), with no significant differences in the CRC incidence (HR 1.6, 95 %CI 0.6 - 3.8). Conclusions: Patients meeting high-risk criteria have a higher incidence of advanced neoplasia during endoscopic surveillance. No differences were found in the CRC incidence at a 3-year surveillance recommendation.

Colonoscopy versus fecal immunochemical testing in colorectal-cancer screening.

BACKGROUND: Colonoscopy and fecal immunochemical testing (FIT) are accepted strategies for colorectal-cancer screening in the average-risk population. METHODS: In this randomized, controlled trial involving asymptomatic adults 50 to 69 years of age, we compared one-time colonoscopy in 26,703 subjects with FIT every 2 years in 26,599 subjects. The primary outcome was the rate of death from colorectal cancer at 10 years. This interim report describes rates of participation, diagnostic findings, and occurrence of major complications at completion of the baseline screening. Study outcomes were analyzed in both intention-to-screen and as-screened populations. RESULTS: The rate of participation was higher in the FIT group than in the colonoscopy group (34.2% vs. 24.6%, P<0.001). Colorectal cancer was found in 30 subjects (0.1%) in the colonoscopy group and 33 subjects (0.1%) in the FIT group (odds ratio, 0.99; 95% confidence interval [CI], 0.61 to 1.64; P=0.99). Advanced adenomas were detected in 514 subjects (1.9%) in the colonoscopy group and 231 subjects (0.9%) in the FIT group (odds ratio, 2.30; 95% CI, 1.97 to 2.69; P<0.001), and nonadvanced adenomas were detected in 1109 subjects (4.2%) in the colonoscopy group and 119 subjects (0.4%) in the FIT group (odds ratio, 9.80; 95% CI, 8.10 to 11.85; P<0.001). CONCLUSIONS: Subjects in the FIT group were more likely to participate in screening than were those in the colonoscopy group. On the baseline screening examination, the numbers of subjects in whom colorectal cancer was detected were similar in the two study groups, but more adenomas were identified in the colonoscopy group. (Funded by Instituto de Salud Carlos III and others; ClinicalTrials.gov number, NCT00906997.).

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.

Walking, biking or sport: how Spanish women attending breast cancer screening meet physical activity recommendations?

BACKGROUND: The aim is to analyse physical activity (PA), the fulfillment recommendation of at least 150 min of moderate PA, through walking/biking (W&B), sport, both types of PA and the factors associated with inactivity by Spanish women who attended breast cancer screening programmes. METHODS: The DDM-Spain is a multicentre cross-sectional study involving 3584 women, aged 45-68, attending screening in seven Spanish cities. Data were collected using a questionnaire, including age, socio-demographic and lifestyle characteristics, family burden and PA. PA was converted into metabolic equivalent of task (METs), categorized as low ≤ 600 METs min per week (m/w), moderate 600-3000 METs m/w and high ≥ 3000 METs m/w. A multivariate logistic regression was performed to identify variables associated with inactivity for each type of PA. RESULTS: No women achieved a high level of PA through sport. 79.2% achieved a high or moderate level of PA by W&B. Lack of sport was associated with being overweight (odds ratio OR = 1.31; 95% confidence interval CI: 1.06 to 1.62), body mass index (BMI) ≥ 30 (OR = 1.85; 95% CI: 1.44 to 2.38), smoking (OR = 1.56; 95% CI: 1.22 to 2.00) and living with a disabled person (OR = 1.64; 95% CI: 1.0 to 2.81), whereas enough sport practice was associated with higher educational or socio-economic level (SEL). Regarding W&B, inactivity was associated with BMI ≥ 30 (OR = 1.91; 95% CI: 1.49 to 2.45) and living with someone >74 (OR = 1.96; 95% CI: 1.48 to 2.58). Inactivity for both types of exercise was associated with a BMI ≥ 30 (OR = 2.13; 95% CI: 1.63 to 2.8), smoking (OR = 1.41; 95% CI: 1.09 to 1.81) and living with someone >74 (OR = 1.69; 95% CI: 1.24 to 2.28). CONCLUSIONS: Family burden and BMI ≥ 30 are inversely associated with both types of PA. W&B is the most common type of PA regardless of educational and SEL.

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.

Rate of detection of advanced neoplasms in proximal colon by simulated sigmoidoscopy vs fecal immunochemical tests.

BACKGROUND & AIMS: We compared the ability of biennial fecal immunochemical testing (FIT) and one-time sigmoidoscopy to detect colon side-specific advanced neoplasms in a population-based, multicenter, nationwide, randomized controlled trial. METHODS: We identified asymptomatic men and women, 50-69 years old, through community health registries and randomly assigned them to groups that received a single colonoscopy examination or biennial FIT. Sigmoidoscopy yield was simulated from results obtained from the colonoscopy group, according to the criteria proposed in the UK Flexible Sigmoidoscopy Trial for colonoscopy referral. Patients who underwent FIT and were found to have ≥75 ng hemoglobin/mL were referred for colonoscopy. Data were analyzed from 5059 subjects in the colonoscopy group and 10,507 in the FIT group. The main outcome was rate of detection of any advanced neoplasm proximal to the splenic flexure. RESULTS: Advanced neoplasms were detected in 317 subjects (6.3%) in the sigmoidoscopy simulation group compared with 288 (2.7%) in the FIT group (odds ratio for sigmoidoscopy, 2.29; 95% confidence interval, 1.93-2.70; P = .0001). Sigmoidoscopy also detected advanced distal neoplasia in a higher percentage of patients than FIT (odds ratio, 2.61; 95% confidence interval, 2.20-3.10; P = .0001). The methods did not differ significantly in identifying patients with advanced proximal neoplasms (odds ratio, 1.17; 95% confidence interval, 0.78-1.76; P = .44). This was probably due to the lower performance of both strategies in detecting patients with proximal lesions (sigmoidoscopy detected these in 19.1% of patients and FIT in 14.9% of patients) vs distal ones (sigmoidoscopy detected these in 86.8% of patients and FIT in 33.5% of patients). Sigmoidoscopy, but not FIT, detected proximal lesions in lower percentages of women (especially those 50-59 years old) than men. CONCLUSIONS: Sigmoidoscopy and FIT have similar limitations in detecting advanced proximal neoplasms, which depend on patients' characteristics; sigmoidoscopy underperforms for women 50-59 years old. Screening strategies should be designed on the basis of target population to increase effectiveness and cost-effectiveness. ClinicalTrials.gov number: NCT00906997.

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.

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.

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.

Relationship of colonoscopy-detected serrated polyps with synchronous advanced neoplasia in average-risk individuals.

BACKGROUND: Serrated cancers account for 10% to 20% of all colorectal cancers (CRC) and more than 30% of interval cancers. The presence of proximal serrated polyps and large (≥10 mm) serrated polyps (LSP) has been correlated with colorectal neoplasia. OBJECTIVE: To evaluate the prevalence of serrated polyps and their association with synchronous advanced neoplasia in a cohort of average-risk population and to assess the efficacy of one-time colonoscopy and a biennial fecal immunochemical test for reducing CRC-related mortality. This study focused on the sample of 5059 individuals belonging to the colonoscopy arm. DESIGN: Multicenter, randomized, controlled trial. SETTING: The ColonPrev study, a population-based, multicenter, nationwide, randomized, controlled trial. PATIENTS: A total of 5059 asymptomatic men and women aged 50 to 69 years. INTERVENTION: Colonoscopy. MAIN OUTCOME MEASUREMENTS: Prevalence of serrated polyps and their association with synchronous advanced neoplasia. RESULTS: Advanced neoplasia was detected in 520 individuals (10.3%) (CRC was detected in 27 [0.5%] and advanced adenomas in 493 [9.7%]). Serrated polyps were found in 1054 individuals (20.8%). A total of 329 individuals (6.5%) had proximal serrated polyps, and 90 (1.8%) had LSPs. Proximal serrated polyps or LSPs were associated with male sex (odds ratio [OR] 2.08, 95% confidence interval [CI], 1.76-4.45 and OR 1.65, 95% CI, 1.31-2.07, respectively). Also, LSPs were associated with advanced neoplasia (OR 2.49, 95% CI, 1.47-4.198), regardless of their proximal (OR 4.15, 95% CI, 1.69-10.15) or distal (OR 2.61, 95% CI, 1.48-4.58) locations. When we analyzed subtypes of serrated polyps, proximal hyperplasic polyps were related to advanced neoplasia (OR 1.61, 95% CI, 1.13-2.28), although no correlation with the location of the advanced neoplasia was observed. LIMITATIONS: Pathology criteria for the diagnosis of serrated polyps were not centrally reviewed. The morphology of the hyperplasic polyps (protruded or flat) was not recorded. Finally, because of the characteristics of a population-based study carried out in average-risk patients, the proportion of patients with CRC was relatively small. CONCLUSION: LSPs, but not proximal serrated polyps, are associated with the presence of synchronous advanced neoplasia. Further studies are needed to determine the risk of proximal hyperplastic polyps.