title: Testing breast cancer serum biomarkers for early detection and prognosis in pre-diagnosis samples.
abstract: BACKGROUND
  Breast cancer is a leading cause of morbidity and mortality worldwide. Although mammography screening is available, there is an ongoing interest in improved early detection and prognosis. Herein, we have analysed a combination of serological biomarkers in a case-control cohort of sera taken before diagnosis.
  
  
  METHODS
  This nested case-control study within the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) used serum samples from 239 women who subsequently developed breast cancer and 239 matched cancer-free controls. Sera were screened by ELISA for 9 candidate markers. Univariate and multivariate analyses were performed to examine associations with clinico-pathological features and between case controls in different time groups before diagnosis.
  
  
  RESULTS
  Significant associations with clinico-pathological features related to prognosis were found for several candidates (CA15-3, HSP90A and PAI-1). However, there were no consistent differences between cases and controls for any candidate in the lead up to diagnosis. Whilst combination models outperformed single markers, there was no increase in performance towards diagnosis.
  
  
  CONCLUSIONS
  This study using unique pre-diagnosis samples shows that CA15-3, HSP90A and PAI-1 have potential as early prognostic markers and warrant further investigation. However, none of the candidates or combinations would be useful for screening.
authors.affiliation: Department of Women's Cancer, Institute for Women's Health, University College London, London, W1T 7DN, UK.
authors.forename: Anna
authors.initials: A
authors.lastname: Kazarian
authors.affiliation: Department of Women's Cancer, Institute for Women's Health, University College London, London, W1T 7DN, UK.
authors.forename: Oleg
authors.initials: O
authors.lastname: Blyuss
authors.affiliation: Department of Biological Sciences, University of Essex, Colchester, Essex CO4 3SQ, UK.
authors.forename: Gergana
authors.initials: G
authors.lastname: Metodieva
authors.affiliation: Department of Women's Cancer, Institute for Women's Health, University College London, London, W1T 7DN, UK.
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Gentry-Maharaj
authors.affiliation: Department of Women's Cancer, Institute for Women's Health, University College London, London, W1T 7DN, UK.
authors.forename: Andy
authors.initials: A
authors.lastname: Ryan
authors.affiliation: Oles Honchar Dnipropetrovsk National University, Dnipropetrovsk, Ukraine.
authors.forename: Elena M
authors.initials: EM
authors.lastname: Kiseleva
authors.affiliation: Oles Honchar Dnipropetrovsk National University, Dnipropetrovsk, Ukraine.
authors.forename: Olga M
authors.initials: OM
authors.lastname: Prytomanova
authors.affiliation: University of New South Wales, Sydney, NSW 2052, Australia.
authors.forename: Ian J
authors.initials: IJ
authors.lastname: Jacobs
authors.affiliation: Department of Women's Cancer, Institute for Women's Health, University College London, London, W1T 7DN, UK.
authors.forename: Martin
authors.initials: M
authors.lastname: Widschwendter
authors.affiliation: Department of Women's Cancer, Institute for Women's Health, University College London, London, W1T 7DN, UK.
authors.forename: Usha
authors.initials: U
authors.lastname: Menon
authors.affiliation: Department of Women's Cancer, Institute for Women's Health, University College London, London, W1T 7DN, UK.
authors.forename: John F
authors.initials: JF
authors.lastname: Timms
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood*; D001943:Breast Neoplasms / Q000097:blood* / Q000175:diagnosis*; D016022:Case-Control Studies; D055088:Early Detection of Cancer / Q000379:methods*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008403:Mass Screening / Q000379:methods; D008875:Middle Aged; D011379:Prognosis; D006113:United Kingdom
chemical_list: D014408:Biomarkers, Tumor