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Where Do Bone-Targeted Agents RANK in Breast Cancer Treatment?
Medical Oncology/Haematology, Kantonsspital Graubünden, Chur 7000, Switzerland
Amgen Ltd., 1 Uxbridge Business Park, Uxbridge UB8 1DH, UK
These authors contributed equally to this work.
* Author to whom correspondence should be addressed.
Received: 12 June 2013; in revised form: 22 July 2013 / Accepted: 25 July 2013 / Published: 28 August 2013
Abstract: Breast cancer cells preferentially metastasise to the skeleton, owing, in part, to the fertile environment provided by bone. Increased bone turnover releases growth factors that promote tumour cell growth. In turn, tumour cells release factors that stimulate further bone turnover, resulting in a vicious cycle of metastasis growth and bone destruction. The RANK-RANK ligand (RANKL) pathway plays a key role in this cycle, and inhibition of RANKL using the fully-human monoclonal antibody denosumab, has demonstrated efficacy in delaying skeletal complications associated with bone metastases in three phase 3 trials. Preclinical studies suggest that the RANKL pathway also plays a role in breast cancer tumourigenesis and migration to bone. In a subgroup analysis of the negative Adjuvant Zoledronic Acid to Reduce Recurrence (AZURE) trial, the bisphosphonate zoledronic acid showed potential for improving survival in patients who were postmenopausal; however, a prospective study in this patient population is required to validate this observation. Ongoing trials are examining whether adjuvant blockade of the RANKL pathway using denosumab can prevent disease recurrence in patients with high-risk breast cancer. These are building on analogous studies that have shown that denosumab improves bone metastasis-free survival in prostate cancer and suggested that it confers an overall survival benefit in non-small-cell lung cancer.
Keywords: RANK ligand; breast neoplasms; bone metastasis; bone metastasis-free survival; adjuvant therapy; skeletal-related event; bone-targeted agents; bisphosphonates; denosumab
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MDPI and ACS Style
von Moos, R.; Haynes, I. Where Do Bone-Targeted Agents RANK in Breast Cancer Treatment? J. Clin. Med. 2013, 2, 89-102.
von Moos R, Haynes I. Where Do Bone-Targeted Agents RANK in Breast Cancer Treatment? Journal of Clinical Medicine. 2013; 2(3):89-102.
von Moos, Roger; Haynes, Ian. 2013. "Where Do Bone-Targeted Agents RANK in Breast Cancer Treatment?" J. Clin. Med. 2, no. 3: 89-102.