Does a higher ratio of serum calcium to magnesium increase the risk for postmenopausal breast cancer?

Breast cancer is the most commonly diagnosed cancer among United States (US) women. Established risk factors explain only about 13% of breast cancer incidence among women in the US. Thus, the cause of most cases of breast cancer remains unknown. In postmenopausal women, serum calcium (Ca) and serum magnesium (Mg) play an important role in skeletal health, cell proliferation and cancer. Mg is essential for DNA duplication and repair and Mg deficiency favors DNA mutations leading to carcinogenesis. Dietary intake of Mg in the US is less than the recommended amount, and the deficit is more pronounced in older individuals where gastrointestinal and renal mechanisms for Mg conservation are not as efficient. Furthermore, healthy postmenopausal women are frequently recommended to take supplemental Ca, but not Mg and vitamin D to maintain bone and overall health. Most women with hormone sensitive breast cancer are recommended to take aromatase inhibitors, which causes bone loss and thus are generally prescribed Ca and vitamin D, but not Mg. Although the association between serum Ca and breast cancer risk remains controversial, we hypothesize that this may be because Mg levels have not been accounted for. Mg level directly influences transient receptor potential melastatin 7 (TRPM7) related Ca influx, calcium-adenosine triphosphatase (Ca-ATP) levels, and cell proliferation, and thereby could lead to cancer. Thus a high serum Ca/Mg ratio is more appropriate and alterations in this ratio could lead to increased development of new and recurrent breast cancer.