title: Early detection of second breast cancers improves prognosis in breast cancer survivors.
abstract: BACKGROUND
  The impact of early detection of second breast cancers in women who have survived a primary breast cancer is unknown. We examined the prognostic effect of detection of ipsilateral breast relapse (IBR) or contralateral breast cancer (CBC) in the asymptomatic relative to symptomatic phase.
  
  
  METHODS
  Subjects were women with histology-verified second (invasive or in situ) breast cancer (N = 1044) in a breast centre in Florence (1980-2005). Symptom status, test, tumour stage, and outcomes data were obtained from clinical records and linkage with mortality registry. Disease-specific survival was measured from first cancer diagnosis to avoid lead-time bias. Sensitivity analysis was used to allow for length-time bias.
  
  
  RESULTS
  Second cancers (IBR = 455; CBC = 589; median age 60 years) were diagnosed in 699 asymptomatic and 345 symptomatic women (67% versus 3%, P < 0.0001). Mammography was more sensitive than clinical examination (86% versus 57%, P < 0.0001); however, 13.8% of cases were only identified clinically. Asymptomatic cancers were smaller than symptomatic for both IBR (P < 0.001) and CBC (P < 0.001). Early-stage tumours were more frequent in asymptomatic (58.1%) than symptomatic (22.6%) women (P < 0.0001). Fewer women with asymptomatic than symptomatic CBC had node metastases (P = 0.0001). Hazard ratio (HR) for asymptomatic (relative to symptomatic) detection was 0.51 (0.32-0.80) for IBR, 0.53 (0.36-0.78) for CBC, and 0.53 (0.40-0.72) in all subjects (P < 0.0001). Length bias-adjusted HRs ranged from 0.53 to 0.73.
  
  
  CONCLUSIONS
  Detection of second breast cancers in the asymptomatic phase leads to detection of early-stage cancer and improves relative survival by between 27% and 47%.
authors.affiliation: Istituto per lo Studio e la Prevenzione Oncologica, Istituto Scientifico della Regione Toscana, Florence, Italy; Screening and Test Evaluation Program, School of Public Health, University of Sydney, Sydney, Australia. Electronic address: nehmath@med.usyd.edu.au.
authors.forename: N
authors.initials: N
authors.lastname: Houssami
authors.affiliation: Istituto per lo Studio e la Prevenzione Oncologica, Istituto Scientifico della Regione Toscana, Florence, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Ciatto
authors.affiliation: Istituto per lo Studio e la Prevenzione Oncologica, Istituto Scientifico della Regione Toscana, Florence, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Martinelli
authors.affiliation: Istituto per lo Studio e la Prevenzione Oncologica, Istituto Scientifico della Regione Toscana, Florence, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Bonardi
authors.affiliation: Cancer Research UK, Centre for Epidemiology, Mathematics and Statistics, Wolfson Institute of Preventive Medicine, London, UK.
authors.forename: S W
authors.initials: SW
authors.lastname: Duffy
mesh_terms: D000368:Aged; D001943:Breast Neoplasms / Q000401:mortality / Q000473:pathology*; D055088:Early Detection of Cancer; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008327:Mammography; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis* / Q000401:mortality; D009367:Neoplasm Staging; D016609:Neoplasms, Second Primary / Q000175:diagnosis* / Q000401:mortality; D011379:Prognosis