Pretreatment Serum Concentration of Vitamin D and Breast Cancer Characteristics: A Prospective Observational Mediterranean Study



      Recent studies of the correlation between breast cancer (BC) and vitamin D yielded contrasting results. Although preclinical and clinical evidence has implicated vitamin D in BC prevention and outcome, little is known about the link between vitamin D and specific BC histologically defined subtypes. In the attempt to clarify this association we correlated vitamin D levels with BC characteristics.

      Patients and Methods

      We enrolled 220 pre- and postmenopausal women with early BC in this prospective observational trial. Data on the patients' clinical and specific BC pathological characteristics were collected and related to vitamin D levels, stratified in deficient (< 20 ng/mL), insufficient (20-30 ng/mL), and sufficient (> 30 ng/mL). BC subtypes were defined according to the 14th St Gallen Breast Cancer Conference.


      Deficient vitamin D levels were correlated with Grade 3 (P = .015) and node-positive (P = .043) BC, and with a higher body mass index (P = .017). Insufficient vitamin D levels were associated with estrogen receptor expression in the primary tumor (P = .033). Vitamin D levels were unrelated to the histological molecular subtypes of BC.


      Deficient vitamin D levels were correlated with more aggressive disease, namely, node-positive high grade BC, and with obesity. Should our findings be confirmed in larger prospective studies, nutritional programs designed to reduce body weight, and vitamin D supplementation might be considered a BC prevention strategy.


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      1. World Health Organization. Breast cancer: prevention and control. Available at: Accessed: June 3, 2017.

        • Coates A.S.
        • Winer E.P.
        • Goldhirsch A.
        • et al.
        Tailoring therapies–improving the management of early breast cancer: St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2015.
        Ann Oncol. 2015; 26: 1533-1546
        • Kemmis C.M.
        • Salvador S.M.
        • Smith K.M.
        • Welsh J.
        Human mammary epithelial cells express CYP27B1 and are growth inhibited by 25-hydroxyvitamin D-3, the major circulating form of vitamin D-3.
        J Nutr. 2006; 136: 887-892
        • Bilinski K.
        • Boyages J.
        Association between 25-hydroxyvitamin D concentration and breast cancer risk in an Australian population: an observational case-control study.
        Breast Cancer Res Treat. 2013; 137: 599-607
        • Wang D.
        • Velez de-la-Paz O.I.
        • Zhai J.X.
        • Liu D.W.
        Serum 25-hydroxy vitamin D and breast cancer risk: a meta-analysis of prospective studies.
        Tumour Biol. 2013; 34: 3509-3517
        • Rose A.A.
        • Elser C.
        • Ennis M.
        • Goodwin P.J.
        Blood levels of vitamin D and early stage breast cancer prognosis: a systematic review and meta-analysis.
        Breast Cancer Res Treat. 2013; 141: 331-339
        • Maalmi H.
        • Ordonez-Mena J.M.
        • Schottker B.
        • Brenner H.
        Serum 25-hydroxyvitamin D levels and survival in colorectal and breast cancer patients: systematic review and meta-analysis of prospective cohort studies.
        Eur J Cancer. 2014; 50: 1510-1521
        • Garland C.F.
        • Kim J.J.
        • Mohr S.B.
        • et al.
        Meta-analysis of all-cause mortality according to serum 25-hydroxyvitamin D.
        Am J Public Health. 2014; 104: e43-e50
        • Kuhn T.
        • Kaaks R.
        • Becker S.
        • et al.
        Plasma 25-hydroxyvitamin D and the risk of breast cancer in the European Prospective Investigation into Cancer and Nutrition: a nested case-control study.
        Int J Cancer. 2013; 133: 1689-1700
        • Cauley J.A.
        • Chlebowski R.T.
        • Wactawski-Wende J.
        • et al.
        Calcium plus vitamin D Supplementation and health outcomes five years after active intervention ended: the Women's Health Initiative.
        J Womens Health. 2013; 22: 915-929
        • Yao S.
        • Sucheston L.E.
        • Millen A.E.
        • et al.
        Pretreatment serum concentrations of 25-hydroxyvitamin D and breast cancer prognostic characteristics: a case-control and a case-series study.
        PLoS One. 2011; 6: e17251
        • Kim H.J.
        • Lee Y.M.
        • Ko B.S.
        • et al.
        Vitamin D deficiency is correlated with poor outcomes in patients with luminal-type breast cancer.
        Ann Surg Oncol. 2011; 18: 1830-1836
        • Bruce D.
        • Yu S.
        • Ooi J.H.
        • Cantorna M.T.
        Converging pathways lead to overproduction of IL-17 in the absence of vitamin D signaling.
        Int Immunol. 2011; 23: 519-528
        • Dogan M.
        • Cesur Y.
        • Zehra Dogan S.
        • Kaba S.
        • Bulan K.
        • Cemek M.
        Oxidant/antioxidant system markers and trace element levels in children with nutritional rickets.
        J Pediatr Endocrinol Metab. 2012; 25: 1129-1139
        • Krishnan A.V.
        • Swami S.
        • Feldman D.
        Vitamin D and breast cancer: inhibition of estrogen synthesis and signaling.
        J Steroid Biochem Mol Biol. 2010; 121: 343-348
        • Nakai K.
        • Fujii H.
        • Kono K.
        • et al.
        Vitamin D activates the Nrf2-Keap1 antioxidant pathway and ameliorates nephropathy in diabetic rats.
        Am J Hypertens. 2014; 27: 586-595
        • Narvaez C.J.
        • Matthews D.
        • LaPorta E.
        • Simmons K.M.
        • Beaudin S.
        • Welsh J.
        The impact of vitamin D in breast cancer: genomics, pathways, metabolism.
        Front Physiol. 2014; 5: 213
        • Zhong W.
        • Gu B.
        • Gu Y.
        • Groome L.J.
        • Sun J.
        • Wang Y.
        Activation of vitamin D receptor promotes VEGF and CuZn-SOD expression in endothelial cells.
        J Steroid Biochem Mol Biol. 2014; 140: 56-62
        • Goodwin P.J.
        • Ennis M.
        • Pritchard K.I.
        • Koo J.
        • Hood N.
        Prognostic effects of 25-hydroxyvitamin D levels in early breast cancer.
        J Clin Oncol. 2009; 27: 3757-3763
        • Neuhouser M.L.
        • Sorensen B.
        • Hollis B.W.
        • et al.
        Vitamin D insufficiency in a multiethnic cohort of breast cancer survivors.
        Am J Clin Nutr. 2008; 88: 133-139
        • Lin J.
        • Manson J.E.
        • Lee I.M.
        • Cook N.R.
        • Buring J.E.
        • Zhang S.M.
        Intakes of calcium and vitamin D and breast cancer risk in women.
        Arch Intern Med. 2007; 167: 1050-1059
        • Palmieri C.
        • MacGregor T.
        • Girgis S.
        • Vigushin D.
        Serum 25-hydroxyvitamin D Levels in early and advanced breast cancer.
        J Clin Pathol. 2006; 59: 1334-1336
        • Chlebowski R.T.
        Vitamin D and breast cancer incidence and outcome.
        Anticancer Agents Med Chem. 2013; 13: 98-106
        • Zinser G.M.
        • McEleney K.
        • Welsh J.
        Characterization of mammary tumor cell lines from wild type and vitamin D3 receptor knockout mice.
        Mol Cell Endocrinol. 2003; 200: 67-80
        • Zinser G.M.
        • Suckow M.
        • Welsh J.
        Vitamin D receptor (VDR) ablation alters carcinogen-induced tumorigenesis in mammary gland, epidermis and lymphoid tissues.
        J Steroid Biochem Mol Biol. 2005; 97: 153-164
        • Lopes N.
        • Sousa B.
        • Martins D.
        • et al.
        Alterations in vitamin D signalling and metabolic pathways in breast cancer progression: a study of VDR, CYP27B1 and CYP24A1 expression in benign and malignant breast lesions.
        BMC Cancer. 2010; 10: 483
        • Banwell C.M.
        • MacCartney D.P.
        • Guy M.
        • et al.
        Altered nuclear receptor corepressor expression attenuates vitamin D receptor signaling in breast cancer cells.
        Clin Cancer Res. 2006; 12: 2004-2013
        • Patel J.B.
        • Patel K.D.
        • Patel S.R.
        • Shah F.D.
        • Shukla S.N.
        • Patel P.S.
        Recent candidate molecular markers: vitamin D signaling and apoptosis specific regulator of p53 (ASPP) in breast cancer.
        Asian Pac J Cancer Prev. 2012; 13: 1727-1735
        • Abulkhair O.
        • Saadeddin A.
        • Makram O.
        • et al.
        Vitamin D levels and breast cancer characteristics: findings in patients from Saudi Arabia.
        J Steroid Biochem Mol Biol. 2016; 164: 106-109
        • Lohmann A.E.
        • Chapman J.A.
        • 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. 2015; 150: 605-611
        • Wortsman J.
        • Matsuoka L.Y.
        • Chen T.C.
        • Lu Z.
        • Holick M.F.
        Decreased bioavailability of vitamin D in obesity.
        Am J Clin Nutr. 2000; 72: 690-693
        • Swami S.
        • Krishnan A.V.
        • Williams J.
        • et al.
        Vitamin D mitigates the adverse effects of obesity on breast cancer in mice.
        Endocr Relat Cancer. 2016; 23: 251-264
        • Duggan C.
        • de Dieu Tapsoba J.
        • Mason C.
        • et al.
        Effect of vitamin D3 supplementation in combination with weight loss on inflammatory biomarkers in postmenopausal women: a randomized controlled trial.
        Cancer Prev Res (Phila). 2015; 8: 628-635