%0 Journal Article
%T The role of bisphosphonates in breast cancer: Actions of bisphosphonates in animal models of breast cancer
%A Susan S Padalecki
%A Theresa A Guise
%J Breast Cancer Research
%D 2001
%I BioMed Central
%R 10.1186/bcr415
%X Up to one-third of patients with early stage breast cancer will eventually die from the disease, and most of these (~80%) will have bone metastases. Although a majority of these bone metastases are destructive or osteolytic, a significant percentage also causes abnormal bone formation or osteosclerotic lesions. Once tumor has metastasized to bone, the disease is incurable. Because the average survival of breast cancer patients following diagnosis of bone metastases is 24¨C36 months, the morbidity of bone pain, fracture, hypercalcemia and nerve compression syndromes is longstanding. Therapeutics to treat and prevent these devastating complications of bone metastases are therefore in great demand.It is well established that the skeleton is the most common site of distant metastases of breast cancer cells. Paget proposed, in 1889, that the affinity of certain cancers to metastasize to bone was due to the fact that the bone provides a 'fertile soil' or environment for the cells to germinate [1]. This seed and soil hypothesis is supported by the fact that bone is a repository for a number of growth factors and that osteoclastic bone resorption releases these growth factors. Histological sections of breast cancer metastases to bone reveal tumor cells adjacent to osteoclasts that are resorbing bone. These observations, combined with the clinical data demonstrating that bisphosphonate inhibitors of bone resorption reduce skeletal morbidity in breast cancer patients, indicate that bone destruction in breast cancer osteolysis is mediated by the osteoclast.Our laboratory and other laboratories have provided evidence of a 'vicious cycle' involving breast cancer and bone. In this vicious cycle, metastatic breast cancer cells in bone produce factors (such as parathyroid hormone-related protein) that stimulate osteoclastic bone resorption. This production results in the release of growth factors, such as transforming growth factor-¦Â, from the bone matrix [2,3]. Growth factors, in t
%K animal models
%K bisphosphonate
%K breast cancer
%K metastases
%K skeletal metastases
%U http://breast-cancer-research.com/content/4/1/35