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.
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Acknowledgments
This work was supported by the Canadian Cancer Society Research Institute; Ontario Institute for Cancer Research; The Breast Cancer Research Foundation and Hold ‘EM For Life Translating Research Discoveries Into Breast Cancer Cures. The study sponsors have no role in the design of the study; the collection, analysis, and interpretation of the data; the writing of the manuscript; and the decision to submit the manuscript for publication.
Ethical Standards
Ethical standards conduct of the MA.21 study was performed in compliance with the research ethics board standards of the National Cancer Institute of Canada Clinical Trials Group and the participating centers. Ethical standards conduct of the vitamin D specific substudy was performed in compliance with the Mount Sinai Hospital Research Ethics Board in Toronto.
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Lohmann, A.E., Chapman, JA.W., Burnell, M.J. et al. 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. Breast Cancer Res Treat 150, 605–611 (2015). https://doi.org/10.1007/s10549-015-3355-x
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DOI: https://doi.org/10.1007/s10549-015-3355-x