title: Prognostic associations of 25 hydroxy vitamin D in NCIC CTG MA.21, a phase III adjuvant randomized clinical trial of three chemotherapy regimens in high-risk breast cancer.
abstract: Low vitamin D levels have been associated with poor breast cancer outcomes in observational studies. We examined the association of vitamin D blood levels with relapse-free survival (RFS), breast cancer-specific survival (BCSS), and overall survival (OS) in the MA.21 randomized clinical trial. Fasting blood was collected pre-chemotherapy in 934/2104 (44.4 %) of subjects; 25 hydroxy vitamin D was measured (radioimmunoassay, Diasorin) in one batch. Vitamin D was assessed as a transformed continuous factor, and categorically (quartiles and clinical classifications). Univariate and multivariate prognostic analyses (adjusted for treatment, stratification factors, and baseline imbalances) were performed using Cox models. Most patients were young (median 47.8 years), white (91.6 %) and premenopausal (69.4 %) with grade III (52 %), HER2 negative or missing (89.5 %), ER positive (61.9 %), T1-2 (89.4 %), N + (72.7 %) breast cancer. Compared to the full population, those with vitamin D levels were more likely to be white, PS 1 or 2, to have undergone mastectomy, and to have an ER + tumor. Mean vitamin D was 69.7 nmol/L (27.9 ng/ml) and did not vary by tumor subtype. The majority (80.5 %) had levels >50 nmol/L (20 ng/ml), considered adequate by Institute of Medicine. Continuous vitamin D was not multivariately associated with RFS, BCSS, or OS (p = 0.36, 0.26, 0.33, respectively); categorical vitamin D was also not associated with outcome. Vitamin D associations with RFS did not differ within ER/HER2 subgroups. There was no evidence that vitamin D blood level was associated with RFS, BCSS, and OS in MA.21; the majority of subjects had adequate vitamin D levels at study entry.
authors.affiliation: Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, 1284-600 University Avenue, Toronto, ON, M5G 1X4, Canada.
authors.forename: Ana Elisa
authors.initials: AE
authors.lastname: Lohmann
authors.forename: Judy-Anne W
authors.initials: JA
authors.lastname: Chapman
authors.forename: Margot J
authors.initials: MJ
authors.lastname: Burnell
authors.forename: Mark Norman
authors.initials: MN
authors.lastname: Levine
authors.forename: Elena
authors.initials: E
authors.lastname: Tsvetkova
authors.forename: Kathleen I
authors.initials: KI
authors.lastname: Pritchard
authors.forename: Karen A
authors.initials: KA
authors.lastname: Gelmon
authors.forename: Patti
authors.initials: P
authors.lastname: O'Brien
authors.forename: Lei
authors.initials: L
authors.lastname: Han
authors.forename: Hope S
authors.initials: HS
authors.lastname: Rugo
authors.forename: Kathy S
authors.initials: KS
authors.lastname: Albain
authors.forename: Edith A
authors.initials: EA
authors.lastname: Perez
authors.forename: Theodore A
authors.initials: TA
authors.lastname: Vandenberg
authors.forename: Haji I
authors.initials: HI
authors.lastname: Chalchal
authors.forename: Ravinder Pal Singh
authors.initials: RP
authors.lastname: Sawhney
authors.forename: Lois E
authors.initials: LE
authors.lastname: Shepherd
authors.forename: Pamela Jean
authors.initials: PJ
authors.lastname: Goodwin
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D006801:Humans; D008875:Middle Aged; D016019:Survival Analysis; D016896:Treatment Outcome; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000097:blood
chemical_list: D014807:Vitamin D; C104450:25-hydroxyvitamin D