Prognostic Significance of Serum Vitamin D Levels in Egyptian Females with Breast Cancer

Abeer Ismail, Rehab El-Awady, Ghada Mohamed, Marwa Hussein, Shimaa Shwaki Ramadan, Abeer Ismail, Rehab El-Awady, Ghada Mohamed, Marwa Hussein, Shimaa Shwaki Ramadan

Abstract

Objective: To determine the frequency and prognostic significance of vitamin D deficiency in Egyptian women with breast cancer (BC). Methods: This prospective study included 50 women with primary invasive, non-metastatic BC. The serum level of 25-hydroxy vitamin D [25(OH)D was measured by ELISA at diagnosis, before any cancer treatment. Vitamin D deficiency was defined as 25(OH) D<20 ng/mL. Patients were followed up for a median of 30 months (range: 18-48). Results: The median level of 25(OH)D was 29.0 ng/mL (range: 10.0-55.0 ng/mL). Fifteen patients (30%) had vitamin D deficiency, which was positively associated with larger tumor size (p < 0.001), higher grade (p = 0.014), advanced stage (p = 0.001), lymph node positivity (p = 0.012), and HER2/neureceptor expression (p = 0.002). It was also linked with worse overall survival (OS) and disease free survival (DFS) (p = 0.026, and p = 0.004, respectively). On multivariate analysis, DFS was independently affected by vitamin D deficiency with an HR of 2.8 (95% CI: 1.6-7.0, p = 0.022) and advanced stage, i.e. stage II had worse survival compared to stage I with an HR of 4.8 (95%CI: 1.1-21.7, p = 0.042). Conclusion: Vitamin D deficiency had a negative effect on overall and disease-free survival in our breast cancer cases, being related to tumor size, stage, grade, nodal status and HER2/neu receptor expression.

Keywords: Vitamine D; cancer breast; prognosis.

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Figures

Figure 1
Figure 1
Overall Survival in Relation to Vitamin D Status
Figure 2
Figure 2
Disease-free Survival in Relation to Vitamin D Status

References

    1. Butt Z, Haider SF, Arif S, et al. Breast cancer risk factors:a comparison between pre-menopausal and post-menopausal women. J Pak Med Assoc. 2012;62:120–4.
    1. Deeb KK, Trump DL, Johnson CS. Vitamin D signalling pathways in cancer:potential for anticancer therapeutics. Nat Rev Cancer. 2007;7:684–700.
    1. Edge SB, Compton CC. The American joint committee on cancer:the 7th edition of the AJCC cancer staging manual and the future of TNM. Ann SurgOncol. 2010;17:1471–4.
    1. Elston CW, Ellis IO. Pathological prognostic factors in breast cancer. I. The value of histological grade in breast cancer:experience from a large study with long-term follow-up. Histopathology. 1991;19:403–10.
    1. Freudenheim JL, Marshall JR, Vena JE, et al. Premenopausal breast cancer risk and intake of vegetables, fruits, and related nutrients. J Natl Cancer Inst. 1996;88:340–8.
    1. Garland CF, Gorham ED, Mohr SB, et al. Vitamin D for cancer prevention:global perspective. Ann Epidemiol. 2009;19:468–83.
    1. Global burden of disease cancer collaboration. Fitzmaurice C, Allen C, et al. Global, regional, and national cancer incidence, mortality, years of life lost, years lived with disability, and disability-adjusted life-years for 32 cancer groups, 1990 to 2015:A systematic analysis for the global burden of disease study. JAMA Oncol. 2017;3:524–48.
    1. Goodwin PJ, Ennis M, Pritchard KI, et al. Prognostic effects of 25-hydroxyvitamin D levels in early breast cancer. J Clin Oncol Off J Am Soc Clin Oncol. 2009;27:3757–63.
    1. Hammond MEH, Hayes DF, Dowsett M, et al. American society of clinical oncology/college of American pathologists guideline recommendations for immunohistochemical testing of estrogen and progesterone receptors in breast cancer (unabridged version) Arch Pathol Lab Med. 2010;134:48–72.
    1. Hatse S, Lambrechts D, Verstuyf A, et al. Vitamin D status at breast cancer diagnosis:correlation with tumor characteristics, disease outcome, and genetic determinants of vitamin D insufficiency. Carcinogenesis. 2012;33:1319–26.
    1. Helzlsouer KJ VDPP steering committee. Overview of the cohort consortium vitamin D pooling project of rarer cancers. Am J Epidemiol. 2010;172:4–9.
    1. Holick MF. Vitamin D deficiency. N Engl J Med. 2007;357:266–81.
    1. Ingraham BA, Bragdon B, Nohe A. Molecular basis of the potential of vitamin D to prevent cancer. Curr Med Res Opin. 2008;24:139–49.
    1. Jacobs ET, Kohler LN, Kunihiro AG, et al. Vitamin D and colorectal, breast, and prostate cancers:A review of the epidemiological evidence. J Cancer. 2016;7:232–40.
    1. Jacobs ET, Thomson CA, Flatt SW, et al. Vitamin D and breast cancer recurrence in the Women's Healthy Eating and Living (WHEL) Study123. Am J ClinNutr. 2011;93:108–17.
    1. Kim HJ, Lee YM, Ko BS, et al. Vitamin D deficiency is correlated with poor outcomes in patients with luminal-type breast cancer. Ann SurgOncol. 2011;18:1830–6.
    1. Kulie T, Groff A, Redmer J, et al. Vitamin D:an evidence-based review. J Am Board Fam Med JABFM. 2009;22:698–706.
    1. Lakhani SR, Ellis IO, Schnitt SJ, et al. Pathology and genetics of tumors of breast and female genital organs. 4th ed. Lyon: IARC Press; 2012. Tumors of the breast in world health organization classification of tumors. .
    1. Lappe JM, Travers-Gustafson D, Davies KM, et al. Vitamin D and calcium supplementation reduces cancer risk:results of a randomized trial. Am J ClinNutr. 2007;85:1586–91.
    1. Lee MM, Lin SS. Dietary fat and breast cancer. Annu Rev Nutr. 2000;20:221–8.
    1. Maalmi H, Ordóñez-Mena JM, Schöttker B, et al. 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 Oxf Engl. 2014;50:1510–21.
    1. Mantell DJ, Owens PE, Bundred NJ, et al. 1 alpha,25-dihydroxyvitamin D(3) inhibits angiogenesis in vitro and in vivo. Circ Res. 2000;87:214–20.
    1. Mathiasen IS, Lademann U, Jäättelä M. Apoptosis induced by vitamin D compounds in hydroxyvitamin breast cancer cells is inhibited by Bcl-2 but does not involve known caspases or p53. Cancer Res. 1999;59:4848–56.
    1. Neuhouser ML, Sorensen B, Hollis BW, et al. Vitamin D insufficiency in a multiethnic cohort of breast cancer survivors. Am J Clin Nutr. 2008;88:133–9.
    1. Norman AW, Bouillon R. Vitamin D nutritional policy needs a vision for the future. Exp Biol Med Maywood NJ. 2010;235:1034–45.
    1. Palmieri C, MacGregor T, Girgis S, et al. Serum 25- D levels in early and advanced breast cancer. J ClinPathol. 2006;59:1334–6.
    1. Santini D, Galluzzo S, Vincenzi B, et al. Longitudinal evaluation of vitamin D plasma levels during anthracycline- and docetaxel-based adjuvant chemotherapy in early-stage breast cancer patients. Ann OncolOff J EurSoc Med Oncol. 2010;21:185–6.
    1. Shaukat N, Jaleel F, Moosa FA, et al. Association between Vitamin D deficiency and breast cancer. Pak J Med Sci. 2017;33:645–9.
    1. Tretli S, Schwartz GG, Torjesen PA, et al. Serum levels of 25-hydroxyvitamin D and survival in Norwegian patients with cancer of breast, colon, lung, and lymphoma:a population-based study. Cancer Causes Control. 2012;23:363–70.
    1. Villaseñor A, Ballard-Barbash R, Ambs A, et al. Associations of serum 25-hydroxyvitamin D with overall and breast cancer-specific mortality in a multiethnic cohort of breast cancer survivors. Cancer Causes Control. 2013;24:759–67.
    1. Vrieling A, Hein R, Abbas S, et al. Serum 25-hydroxyvitamin D and postmenopausal breast cancer survival:a prospective patient cohort study. Breast Cancer Res BCR. 2011;13:R74.
    1. Vrieling A, Seibold P, Johnson TS, et al. Circulating 25-hydroxyvitamin D and postmenopausal breast cancer survival:Influence of tumor characteristics and lifestyle factors? Int J Cancer. 2014;134:2972–83.
    1. Wolff AC, Hammond MEH, Hicks DG, et al. Recommendations for human epidermal growth factor receptor 2 testing in breast cancer:American society of clinical oncology/college of American pathologists clinical practice guideline update. J ClinOncol Off J Am Soc Clin Oncol. 2013;31:3997–4013.
    1. Yang XR, Chang-Claude J, Goode EL, et al. Associations of breast cancer risk factors with tumor subtypes:a pooled analysis from the breast cancer association consortium studies. J Natl Cancer Inst. 2011;103:250–63.
    1. Yao S, Ambrosone CB. Associations between vitamin D deficiency and risk of aggressive breast cancer in African-American women. J Steroid Biochem Mol Biol. 2013;136:337–41.

Source: PubMed

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