title: Molecular profiles of screen detected vs. symptomatic breast cancer and their impact on survival: results from a clinical series.
abstract: BACKGROUND
  Stage shift is widely considered a major determinant of the survival benefit conferred by breast cancer screening. However, factors and mechanisms underlying such a prognostic advantage need further clarification. We sought to compare the molecular characteristics of screen detected vs. symptomatic breast cancers and assess whether differences in tumour biology might translate into survival benefit.
  
  
  METHODS
  In a clinical series of 448 women with operable breast cancer, the Kaplan-Meier method and the log-rank test were used to estimate the likelihood of cancer recurrence and death. The Cox proportional hazard model was used for the multivariate analyses including mode of detection, age at diagnosis, tumour size, and lymph node status. These same models were applied to subgroups defined by molecular subtypes.
  
  
  RESULTS
  Screen detected breast cancers tended to show more favourable clinicopathological features and survival outcomes compared to symptomatic cancers. The luminal A subtype was more common in women with mammography detected tumours than in symptomatic patients (68.5 vs. 59.0%, p=0.04). Data analysis across categories of molecular subtypes revealed significantly longer disease free and overall survival for screen detected cancers with a luminal A subtype only (p=0.01 and 0.02, respectively). For women with a luminal A subtype, the independent prognostic role of mode of detection on recurrence was confirmed in Cox proportional hazard models (p=0.03). An independent role of modality of detection on survival was also suggested (p=0.05).
  
  
  CONCLUSIONS
  Molecular subtypes did not substantially explain the differences in survival outcomes between screened and symptomatic patients. However, our results suggest that molecular profiles might play a role in interpreting such differences at least partially.Further studies are warranted to reinterpret the efficacy of screening programmes in the light of tumour biology.
authors.affiliation: Epidemiology Unit, National Cancer Institute G, Pascale Foundation, Via Mariano Semmola, Naples 80131, Italy. anna.crispo@tin.it
authors.forename: Anna
authors.initials: A
authors.lastname: Crispo
authors.forename: Maddalena
authors.initials: M
authors.lastname: Barba
authors.forename: Giuseppe
authors.initials: G
authors.lastname: D'Aiuto
authors.forename: Michelino
authors.initials: M
authors.lastname: De Laurentiis
authors.forename: Maria
authors.initials: M
authors.lastname: Grimaldi
authors.forename: Massimo
authors.initials: M
authors.lastname: Rinaldo
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Caolo
authors.forename: Massimiliano
authors.initials: M
authors.lastname: D'Aiuto
authors.forename: Immacolata
authors.initials: I
authors.lastname: Capasso
authors.forename: Emanuela
authors.initials: E
authors.lastname: Esposito
authors.forename: Alfonso
authors.initials: A
authors.lastname: Amore
authors.forename: Maurizio
authors.initials: M
authors.lastname: Di Bonito
authors.forename: Gerardo
authors.initials: G
authors.lastname: Botti
authors.forename: Maurizio
authors.initials: M
authors.lastname: Montella
mesh_terms: D000328:Adult; D000368:Aged; D000951:Antigens, Neoplasm / Q000032:analysis; D014408:Biomarkers, Tumor / Q000378:metabolism; D001943:Breast Neoplasms / Q000175:diagnosis / Q000378:metabolism / Q000401:mortality* / Q000473:pathology; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006801:Humans; D008403:Mass Screening / Q000379:methods; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D018709:Statistics, Nonparametric; D016019:Survival Analysis
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor