Hypercalcemia in breast cancer: an echo of bone mobilization during lactation?
Hypercalcemia is a frequent complication of breast cancer which causes significant morbidity and mortality. Most commonly, it occurs in patients with multiple skeletal metastases. However, in a significant minority of patients, calcium levels become elevated in the absence of skeletal disease. In both instances, hypercalcemia is the result of pathological bone resorption caused by the secretion of cytokines that stimulate osteoclast differentiation and activity. One of these cytokines is parathyroid hormone-related protein (PTHrP). PTHrP is also secreted by normal breast cells during lactation to increase bone resorption and liberate skeletal calcium stores for the purposes of milk production. Therefore, the pathophysiology of hypercalcemia in breast cancer patients mimics the physiological processes that normally regulate calcium metabolism during lactation. Current therapy for hypercalcemia in breast cancer patients relies on the inhibition of bone resorption by a class of drugs known as bisphophonates. Newer therapies in development target cytokines involved in the recruitment and activation of osteoclasts by tumor cells.
DeMauro
Samantha
S
Section of Endocrinology and Metabolism, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520, USA.
Wysolmerski
John
J
D000818:Animals; D001842:Bone and Bones / Q000378:metabolism*; D001943:Breast Neoplasms / Q000150:complications* / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D005260:Female; D005544:Forecasting; D006801:Humans; D006934:Hypercalcemia / Q000209:etiology / Q000378:metabolism*; D007774:Lactation; D010010:Osteoclasts / Q000187:drug effects; D010014:Osteolysis / Q000209:etiology* / Q000378:metabolism; D044162:Parathyroid Hormone-Related Protein / Q000276:immunology / Q000378:metabolism; D011247:Pregnancy; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology
D044162:Parathyroid Hormone-Related Protein; D014409:Tumor Necrosis Factor-alpha; D002118:Calcium