Serum calcium and breast cancer risk: results from a prospective cohort study of 7,847 women

Abstract

Experimental and epidemiological studies suggest that calcium-regulating hormonesparathyroid hormone (PTH) and vitamin D -may be associated with breast cancer risk.No prospective cohort study has investigated the association between pre-diagnostic calcium levels and subsequent risk of breast cancer. We have examined this in a cohort of 7847 women where serum calcium levels and established risk factors for breast cancer had been assessed at baseline. During a mean follow-up of 17.8 years, 437 incident breast cancer cases were diagnosed. Incidence of breast cancer was calculated in different quartiles of serum calcium levels and a Cox's proportional hazards analysis was used to obtain corresponding relative risks (RR), with a 95% confidence interval (CI), adjusted for potential confounders.In premenopausal women, serum calcium levels were inversely associated with breast cancer risk in a dose-response manner. The adjusted RR (95% CI) of breast cancer was in the 2 nd calcium quartile 0.91 (0.65-1.30), in the 3 rd quartile 0.89 (0.60-1.31), and in the 4 th quartile 0. 56 (0.32-0.98), as compared to the 1 st calcium quartile. In postmenopausal overweight women (BMI>25), breast cancer risk was higher in calcium quartiles 2 to 4 as compared to the 1 st quartile. Our findings may have implications for primary prevention of breast cancer and for the management of asymptomatic primary hyperparathyroidism.

The role of serum 25-hydroxyvitamin D, ionized calcium and phosphorus in breast cancer females: A case-control study

“…Our results agreed with Engel et al [23] and Rejnmark et al [24] and disagreed with Eliassen et al [25] and Almquist et al [14]. In the present study, serum 25(OH)D showed a significant odd's ratio (0.0937,95% CI =0.0311-0.2823) which indicated that individuals with serum levels of 25(OH) D ≥ 66.73 ng/dl having a lower risk of getting breast cancer than those having 25 (OH)D levels <66.73 ng/dl.…”

“…Our results agreed with Engel et al [23] and Rejnmark et al [24]. On the other hand, our results disagreed with Eliassen et al [25] and Almquist et al [14] who found non-significant association between 25(OH) D level and breast cancer risk.…”

“…Several studies have shown that calcitriol (1,25(OH)2D3) inhibits the growth of human breast cancer cell lines, induces differentiation and apoptosis in breast cancer cells, inhibits invasion and metastasis, has an anti-inflammatory effect, inhibits estrogen synthesis and signaling and suppresses aromatase expression directly or indirectly through inhibition of prostaglandins synthesis and expression [13]. It has been argued that free (ionized) calcium provides the best indication of calcium status because it is biologically active and tightly regulated by calcium-regulating hormones [14]. Calcium signals induced by the Ca 2+ regulatory hormone 1, 25-dihydroxyvitamin D3 (1, 25(OH) 2D3) are critical in determining the fate of cancer cells.…”

Vitamin D and calcium insufficiency-related chronic diseases: molecular and cellular pathophysiology

“…A role for functional CaR in breast cancer can be inferred from the fact that in pre-menopausal women, the serum calcium levels vary inversely with breast cancer risk in a concentration-dependent manner (Almquist et al, 2007). Both normal and malignant mammary gland epithelial cells are endowed with the CaR (Cheng et al, 1998).…”

Calcium, Ca2+-Sensing Receptor and Breast Cancer

“…Given the emerging interest in the potential role of Ca 2+ in the etiology of breast cancer, several investigations focus on analyzing the relationship between the levels of serum calcium and the risk of breast cancer. In 2007, the first cohort study of 7847 women performed by Almquist et al (33) evaluated serum calcium in relation to breast cancer risk. They found a positive association between total calcium and breast cancer risk among overweight postmenopausal women.…”