title: Vitamin D status at breast cancer diagnosis: correlation with tumor characteristics, disease outcome, and genetic determinants of vitamin D insufficiency.
abstract: We correlated serum 25-hydroxyvitamin D(3) (25OHD) levels with tumor characteristics and clinical disease outcome in breast cancer patients and assessed the impact of genetic determinants of vitamin D insufficiency. We collected serum from 1800 early breast cancer patients at diagnosis, measured 25OHD by radioimmunoassay (RIA), and determined genetic variants in vitamin D-related genes by Sequenom. Multivariable regression models were used to correlate 25OHD levels with tumor characteristics. Cox proportional hazard models were used to assess overall survival (OS), disease-specific survival (DSS), and disease-free interval (DFI). Lower 25OHD serum levels significantly correlated with larger tumor size at diagnosis (P = 0.0063) but not with lymph node invasion, receptor status, or tumor grade. Genetic variants in 25-hydroxylase (CYP2R1) and vitamin D-binding (DBP) protein significantly determined serum 25OHD levels but did not affect the observed association between serum 25OHD and tumor size. High serum 25OHD (>30 ng/mL) at diagnosis significantly correlated with improved OS (P = 0.0101) and DSS (P = 0.0192) and additionally had a modest effect on DFI, which only became apparent after at least 3 years of follow-up. When considering menopausal status, serum 25OHD had a strong impact on breast cancer-specific outcome in postmenopausal patients [hazards ratios for 25OHD >30 ng/mL versus ≤30 ng/mL were 0.15 (P = 0.0097) and 0.43 (P = 0.0172) for DSS and DFI, respectively], whereas no association could be demonstrated in premenopausal patients. In conclusion, high vitamin D levels at early breast cancer diagnosis correlate with lower tumor size and better OS, and improve breast cancer-specific outcome, especially in postmenopausal patients.
authors.affiliation: Laboratory of Experimental Oncology (LEO), Department of Oncology, KU Leuven, University Hospitals Leuven, Leuven Cancer Institute, Belgium.
authors.forename: Sigrid
authors.initials: S
authors.lastname: Hatse
authors.forename: Diether
authors.initials: D
authors.lastname: Lambrechts
authors.forename: Annemieke
authors.initials: A
authors.lastname: Verstuyf
authors.forename: Ann
authors.initials: A
authors.lastname: Smeets
authors.forename: Barbara
authors.initials: B
authors.lastname: Brouwers
authors.forename: Thijs
authors.initials: T
authors.lastname: Vandorpe
authors.forename: Olivier
authors.initials: O
authors.lastname: Brouckaert
authors.forename: Gilian
authors.initials: G
authors.lastname: Peuteman
authors.forename: Annouschka
authors.initials: A
authors.lastname: Laenen
authors.forename: Lieve
authors.initials: L
authors.lastname: Verlinden
authors.forename: Carsten
authors.initials: C
authors.lastname: Kriebitzsch
authors.forename: Anne-Sophie
authors.initials: AS
authors.lastname: Dieudonné
authors.forename: Robert
authors.initials: R
authors.lastname: Paridaens
authors.forename: Patrick
authors.initials: P
authors.lastname: Neven
authors.forename: Marie-Rose
authors.initials: MR
authors.lastname: Christiaens
authors.forename: Roger
authors.initials: R
authors.lastname: Bouillon
authors.forename: Hans
authors.initials: H
authors.lastname: Wildiers
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000097:blood* / Q000175:diagnosis; D005260:Female; D006801:Humans; D008875:Middle Aged; D015999:Multivariate Analysis; D014807:Vitamin D / Q000097:blood*; D014808:Vitamin D Deficiency / Q000097:blood*
chemical_list: D014807:Vitamin D