Serum 25(OH) Vitamin D and Risk of Breast Cancer: A Nested Case-Control Study from the French E3N Cohort

Abstract

Background: High 25-hydroxyvitamin D [25(OH)D] serum concentrations have been found to be associated with reduced breast cancer risk. However, few studies have further investigated this relationship according to menopausal status, nor have they taken into account factors known to influence vitamin D status, such as dietary and serum calcium, parathyroid hormone, and estradiol serum levels.Methods: We designed a nested case-control study within the French E3N cohort. Cases were women diagnosed with incident breast cancer (n = 636). Controls (n = 1,272) were matched with cases on age, menopausal status at blood collection, age at menopause, and center and year of blood collection. Multivariate logistic regression models were established.Results: We found a decreased risk of breast cancer with increasing 25(OH) vitamin D 3 serum concentrations (odds ratio, 0.73; 95% confidence interval, 0.55-0.96; P trend = 0.02) among women in the highest tertile. We also observed a significant inverse association restricted to women under 53 years of age at blood sampling [odds ratio (T 3 versus T 1 ), 0.60; 95% confidence interval, 0.37-0.98; P trend = 0.04]. In premenopausal women, the risk was also decreased, although not significantly.Conclusion: Our findings support a decreased risk of breast cancer associated with high 25(OH) vitamin D 3 serum concentrations, especially in younger women, although we were unable to confirm a direct influence of age or menopausal status.Impact: Randomized intervention trials with vitamin D supplementation are required to confirm its benefits on breast cancer risk, but the maintenance of adequate vitamin D levels should be encouraged by public health policy. Cancer Epidemiol Biomarkers Prev; 19(9); 2341-50. ©2010 AACR.

Plasma 25‐hydroxyvitamin D and the risk of breast cancer in the European prospective investigation into cancer and nutrition: A nested case–control study

“…29 The results of these studies contributed to the result of the most recent meta-analysis 16 that revealed an inverse overall risk estimate from six prospective studies. 11,19,23,[29][30][31] However, the clear null results of our study and two other recent studies 20,21 suggest that the prospective overall relationship of 25(OH)D levels and breast cancer risk is weak in magnitude, if present at all.…”

“…These cases were also part of a parallel initiative based on a total of 636 incident cases from the E3N study that independently started at the same time as our study. 19 An incidence density protocol was applied for matching. Accordingly, each control could be chosen more than once and also become a case at a later time point.…”

“…Moreover, we carried out a priori-defined analyses stratified by menopausal status at blood donation, HRT use at blood donation, season and country. The analysis stratified by menopausal status was conducted, as one previous study had shown an interaction between 25(OH)D levels and menopausal status, 19 while most prospective studies consisted of predominantly postmenopausal women. HRT use was considered for stratified analyses, because HRT has been proposed to interfere with vitamin D signaling in relation to breast cancer risk.…”

“…16 However, 25(OH)D levels were significantly inversely associated with breast cancer risk in only one of the original studies included in the latter meta-analysis, the French E3N cohort, which is part of the multicenter European Prospective Investigation into Cancer and Nutrition (EPIC). 19 As no significant associations were observed in two further prospective studies that were published after both meta-analyses, 20,21 the evidence from prospective studies on a relationship between 25(OH)D levels and breast cancer risk remains inconclusive. Therefore, our first objective was to investigate the prospective relationship between 25(OH)D levels and breast cancer risk in a larger EPIC-wide prospective case-control study.…”

Antineoplastic effects of 1,25(OH)2D3 and its analogs in breast, prostate and colorectal cancer

“…This reduced BC risk was even more pronounced in premenopausal women. Another European study also found an inverse association between BC risk and 25(OH)D 3 serum levels after a follow-up of w10 years, which was also more pronounced in younger women (Engel et al 2010). On the other hand, a Swedish study found a weak association after a follow-up of 10-15 years (Almquist et al 2010).…”