Calcium Metabolism and Breast Cancer: Echoes of Lactation?

Lactation requires a series of adaptations in maternal calcium and bone metabolism to ensure a steady supply of calcium to the lactating mammary gland. The alterations in systemic metabolism are accompanied by alterations in the expression of calcium receptors, channels, binding proteins, pumps and transporters in mammary epithelial cells to increase the uptake of calcium from the extracellular fluid and to transport it into milk. Intracellular calcium regulates signaling pathways that mediate changes in cell proliferation, differentiation and death and many of the molecules involved in supporting and coordinating calcium secretion into milk are re-expressed and redeployed to support malignant behavior in breast cancer cells. In this article, we review adaptations of systemic calcium homeostasis during lactation, as well as the mechanisms of milk calcium transport. We then discuss how reactivation of these pathways contributes to the pathophysiology of breast cancer.