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.

Circulating 25-hydroxyvitamin D Levels and Prognosis among Cancer Patients: A Systematic Review

“…15-20; Table 1). Elevated circulating 25-OHD concentrations were associated with statistically significantly better survival in two studies (15,19), borderline statistically significant better survival in two (16,18), and no associations in last two (17,20). In one of the studies, lower circulating 25-OHD concentrations were associated with reduced survival among women who did not have chemotherapy [HR ¼ 1.15; 95% (15,17,19).…”

“…Elevated circulating 25-OHD concentrations were associated with statistically significantly better survival in two studies (15,19), borderline statistically significant better survival in two (16,18), and no associations in last two (17,20). In one of the studies, lower circulating 25-OHD concentrations were associated with reduced survival among women who did not have chemotherapy [HR ¼ 1.15; 95% (15,17,19). Circulating 25-OHD was associated with breast cancer survival in two of the other three studies (15,19), but the effect was limited to postmenopausal (HR, 0.15; 95% CI, 0.03-0.63), and not premenopausal women (HR, 0.93; 95% CI, 0.43-2.02) in one study (19).…”

Vitamin D Levels in Patients with Breast Cancer: Importance of Dressing Style

“…A 4-year, populationbased, double-blind, randomized placebo-controlled trial has shown that improving calcium and vitamin D nutritional status substantially reduces all-cancer risk in postmenopausal women (Lappe et al, 2007). In addition to preventional role of vitamin D in BC development, various studies and a large cohort study investigating the association between vitamin D and BC survival have shown that women with vitamin D deficiency had a worse outcome (Robsahm et al, 2004;Porojnicu et al, 2007;Goodwin et al, 2009;Hatse et al, 2012). Additionally, it has been reported that 25-OHD levels were significantly lower in patients with locally advanced or metastatic BC patients (Palmieri et al, 2006).…”

Aromatase inhibitors in the breast cancer clinic: focus on exemestane

“…Another emerging hypothesis proposes a role for vitamin D. Indeed vitamin D deficiency is common in postmenopausal breast cancer patients and is associated with worse outcome (Hatse et al 2012). Consequently, recent studies have reported that daily vitamin D supplements may have a protective effect on pathogenesis (Khan et al 2010, Rastelli et al 2011.…”