Association between vitamin D and calcium intake and breast cancer risk according to menopausal status and receptor status in Japan

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.