Correlation of mammographic density and serum calcium levels in patients with primary breast cancer

Percentage mammographic breast density (PMD) is one of the most important risk factors for breast cancer (BC). Calcium, vitamin D, bisphosphonates, and denosumab have been considered and partly confirmed as factors potentially influencing the risk of BC. This retrospective observational study investigated the association between serum calcium level and PMD. A total of 982 BC patients identified in the research database at the University Breast Center for Franconia with unilateral BC, calcium and albumin values, and mammogram at the time of first diagnosis were included. PMD was assessed, using a semiautomated method by two readers. Linear regression analyses were conducted to investigate the impact on PMD of the parameters of serum calcium level adjusted for albumin level, and well-known clinical predictors such as age, body mass index (BMI), menopausal status and confounder for serum calcium like season in which the BC was diagnosed. Increased calcium levels were associated with reduced PMD (P = 0.024). Furthermore, PMD was inversely associated with BMI (P < 0.001) and age (P < 0.001). There was also an association between PMD and menopausal status (P < 0.001). The goodness-of-fit of the regression model was moderate. This is the first study assessing the association between serum calcium level and PMD. An inverse association with adjusted serum calcium levels was observed. These findings add to previously published data relating to vitamin D, bisphosphonates, denosumab, and the RANK/RANKL signaling pathway in breast cancer risk and prevention.