title: Impact of risk factors on different interval cancer subtypes in a population-based breast cancer screening programme.
abstract: 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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Epidemiology and Evaluation, IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain; European Higher Education Area (EHEA) Doctoral Programme in Public Health in Department of Pediatrics, Obstetrics and Gynecology, Preventive Medicine and Public Health, Universitat Autònoma de Barcelona (UAB), Bellaterra, Barcelona, Spain.
authors.forename: Jordi
authors.initials: J
authors.lastname: Blanch
authors.affiliation: Department of Epidemiology and Evaluation, IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain; European Higher Education Area (EHEA) Doctoral Programme in Public Health in Department of Pediatrics, Obstetrics and Gynecology, Preventive Medicine and Public Health, Universitat Autònoma de Barcelona (UAB), Bellaterra, Barcelona, Spain; Research network on health services in chronic diseases (REDISSEC), Barcelona, Spain.
authors.forename: Maria
authors.initials: M
authors.lastname: Sala
authors.affiliation: General Directorate Public Health, Valencia, Spain; Centre for Public Health Research (CSISP), FISABIO, Valencia, Spain.
authors.forename: Josefa
authors.initials: J
authors.lastname: Ibáñez
authors.affiliation: Department of Epidemiology and Evaluation, IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain; Research network on health services in chronic diseases (REDISSEC), Barcelona, Spain.
authors.forename: Laia
authors.initials: L
authors.lastname: Domingo
authors.affiliation: Galician Breast Cancer Screening Programme, Directorate for innovation and management of public health, Santiago de Compostela, Spain.
authors.forename: Belén
authors.initials: B
authors.lastname: Fernandez
authors.affiliation: Osakidetza Breast Cancer Screening Programme, Basque Country Health Service, Bilbao, Spain.
authors.forename: Arantza
authors.initials: A
authors.lastname: Otegi
authors.affiliation: General Directorate of Health Care Programmes, Canary Islands Health Service, Las Palmas de Gran Canaria, Spain.
authors.forename: Teresa
authors.initials: T
authors.lastname: Barata
authors.affiliation: Galician Breast Cancer Screening Programme, Directorate for innovation and management of public health, Santiago de Compostela, Spain.
authors.forename: Raquel
authors.initials: R
authors.lastname: Zubizarreta
authors.affiliation: Department of Radiology, Hospital de Santa Caterina, Salt, Girona, Spain.
authors.forename: Joana
authors.initials: J
authors.lastname: Ferrer
authors.affiliation: Department of Epidemiology and Evaluation, IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain; European Higher Education Area (EHEA) Doctoral Programme in Public Health in Department of Pediatrics, Obstetrics and Gynecology, Preventive Medicine and Public Health, Universitat Autònoma de Barcelona (UAB), Bellaterra, Barcelona, Spain; Research network on health services in chronic diseases (REDISSEC), Barcelona, Spain.
authors.forename: Xavier
authors.initials: X
authors.lastname: Castells
authors.affiliation: Research network on health services in chronic diseases (REDISSEC), Barcelona, Spain; Department of Basic Medical Sciences, Biomedical Research Institut of Lleida (IRBLLEIDA)-University of Lleida, Lleida, Spain.
authors.forename: Montserrat
authors.initials: M
authors.lastname: Rué
authors.affiliation: General Directorate Public Health, Valencia, Spain; Centre for Public Health Research (CSISP), FISABIO, Valencia, Spain.
authors.forename: Dolores
authors.initials: D
authors.lastname: Salas
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000145:classification / Q000175:diagnosis* / Q000473:pathology; D055088:Early Detection of Cancer; D005188:False Negative Reactions; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008327:Mammography; D008403:Mass Screening; D008875:Middle Aged; D016016:Proportional Hazards Models; D012307:Risk Factors