Abstract

Although several studies have investigated the possible association between elevated vitamin D and calcium intake and low breast cancer risk, findings have been inconsistent. We conducted a case-control study to clarify the association between vitamin D and calcium intake and breast cancer risk among pre- and post- menopausal women in Japan. We also investigated whether these effects were modified by tumor receptor status, specifically estrogen receptor (ER), progesterone receptor (PR), or human epidermal growth factor receptor-2 (HER2) status. We examined 1803 breast cancer patients and 3606 age- and menopausal status-matched noncancer controls. Among cases, 713 were assessed for ER, PR, and HER2 status. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated using conditional or unconditional logistic models adjusted for potential confounders. A significant inverse association was observed between vitamin D and calcium intake and breast cancer risk among all subjects, with top quartile ORs of 0.76 (95% CI, 0.63-0.90; trend P = 0.001) and 0.83 (95% CI, 0.69-0.99; trend P = 0.038), respectively. In analyses stratified by menopausal status, a significant association between risk and vitamin D was observed only among premenopausal women (trend P < 0.001), whereas that between risk and calcium intake was seen only among postmenopausal women (trend P = 0.022). Heterogeneity by menopausal status for these associations was statistically significant. This association was modified by tumor receptor status. These findings suggest that the protective effects of vitamin D and calcium intake against breast cancer risk may differ by menopausal status and receptor status. (Cancer Sci 2010).

Abstract

BACKGROUND: Some evidence suggests that vitamin D may reduce breast cancer risk. Despite the biological interaction between vitamin D and calcium, few studies have evaluated their joint effects on breast cancer risk.

OBJECTIVE: The objective was to evaluate the associations and potential interaction between vitamin D and calcium (from food and supplements) and breast cancer risk in a population-based case-control study.

DESIGN: Breast cancer cases aged 25-74 y (diagnosed 2002-2003) were identified through the Ontario Cancer Registry. Controls were identified by using random digit dialing; 3101 cases and 3471 controls completed epidemiologic and food-frequency questionnaires. Adjusted odds ratios (ORs) and 95% CIs were estimated by using multivariate logistic regression.

RESULTS: Vitamin D and calcium intakes from food only and total combined intakes (food and supplements) were not associated with breast cancer risk, although the mean intake of vitamin D was low. Vitamin D supplement intake >10 mug/d (400 IU/d) compared with no intake was associated with a reduced risk of breast cancer (adjusted OR: 0.76; 95% CI: 0.59, 0.98). No categories of calcium supplement intake were significantly associated with reduced breast cancer risk, but a significant inverse trend was observed (P = 0.04). There were no significant interactions involving vitamin D, calcium, or menopausal status.

CONCLUSIONS: No associations were found between overall vitamin D or calcium intake and breast cancer risk. Vitamin D from supplements was independently associated with reduced breast cancer risk. Further research is needed to investigate the effects of higher doses of vitamin D and calcium supplements.