Bone metastasis

Abstract: A search for general regulators of cancer metastasis has yielded a set of microRNAs for which expression is specifically lost as human breast cancer cells develop metastatic potential. Here we show that restoring the expression of these microRNAs in malignant cells suppresses lung and bone metastasis by human cancer cells in vivo. Of these microRNAs, miR-126 restoration reduces overall tumour growth and proliferation, whereas miR-335 inhibits metastatic cell invasion. miR-335 regulates a set of genes whose collective expression in a large cohort of human tumours is associated with risk of distal metastasis. miR-335 suppresses metastasis and migration through targeting of the progenitor cell transcription factor SOX4 and extracellular matrix component tenascin C. Expression of miR-126 and miR-335 is lost in the majority of primary breast tumours from patients who relapse, and the loss of expression of either microRNA is associated with poor distal metastasis-free survival. miR-335 and miR-126 are thus identified as metastasis suppressor microRNAs in human breast cancer.

Abstract: Aim: The goal of this study was to estimate the cumulative activity of 131I to be administered to patients with distant metastases from thyroid carcinoma. Methods: A total of 444 patients were treated from 1953–1994 for distant metastases from papillary and follicular thyroid carcinoma: 223 had lung metastases only, 115 had bone metastases only, 82 had both lung and bone metastases, and 24 had metastases at other sites. Treatment consisted of the administration of 3.7 GBq (100 mCi) 131I after withdrawal of thyroid hormone treatment, every 3–9 months during the first 2 yr and then once a year until the disappearance of any metastatic uptake. Thyroxine treatment was given at suppressive doses between 131I treatment courses. Results: Negative imaging studies (negative total body 131I scans and conventional radiographs) were attained in 43% of the 295 patients with 131I uptake; more frequently in those who were younger, had well-differentiated tumors, and had a limited extent of disease. Most negative studies...

Abstract: Purpose This randomized study compared denosumab, a fully human monoclonal antibody against receptor activator of nuclear factor B (RANK) ligand, with zoledronic acid in delaying or preventing skeletal-related events (SREs) in patients with breast cancer with bone metastases. Patients and Methods Patients were randomly assigned to receive either subcutaneous denosumab 120 mg and intravenous placebo (n 1,026) or intravenous zoledronic acid 4 mg adjusted for creatinine clearance and subcutaneous placebo (n 1,020) every 4 weeks. All patients were strongly recommended to take daily calcium and vitamin D supplements. The primary end point was time to first on-study SRE (defined as pathologic fracture, radiation or surgery to bone, or spinal cord compression). Results Denosumab was superior to zoledronic acid in delaying time to first on-study SRE (hazard ratio, 0.82; 95% CI, 0.71 to 0.95; P .01 superiority) and time to first and subsequent (multiple) on-study SREs (rate ratio, 0.77; 95% CI, 0.66 to 0.89; P .001). Reduction in bone turnover markers was greater with denosumab. Overall survival, disease progression, and rates of adverse events (AEs) and serious AEs were similar between groups. An excess of renal AEs and acute-phase reactions occurred with zoledronic acid; hypocalcemia occurred more frequently with denosumab. Osteonecrosis of the jaw occurred infrequently (2.0%, denosumab; 1.4%, zoledronic acid; P .39). Conclusion Denosumab was superior to zoledronic acid in delaying or preventing SREs in patients with breast cancer metastatic to bone and was generally well tolerated. With the convenience of a subcutaneous injection and no requirement for renal monitoring, denosumab represents a potential treatment option for patients with bone metastases. J Clin Oncol 28:5132-5139. © 2010 by American Society of Clinical Oncology

Abstract: The skeleton is the most common organ to be affected by metastatic cancer, and tumors arising from the breast, prostate, thyroid, lung, and kidney possess a special propensity to spread to bone. Breast carcinoma, the most prevalent malignancy, causes the greatest morbidity. Of great clinical importance is the observation that metastatic bone disease may remain confined to the skeleton. In these patients, the decline in quality of life and eventual death is due almost entirely to skeletal complications and their subsequent treatment. Bone pain is the most common complication of metastatic bone disease, resulting from structural damage, periosteal irritation, and nerve entrapment. Recent evidence suggests that pain caused by bone metastasis may also be related to the rate of bone resorption. Hypercalcemia occurs in 5-10% of all patients with advanced cancer but is most common in patients with breast carcinoma, multiple myeloma, and squamous carcinomas of the lung and other primary sites. Pathologic fractures are a relatively late complication of bone involvement. The clinical courses of breast and prostate carcinoma are relatively long, with a median survival of 2-3 years. For patients with breast carcinoma, good prognostic factors for survival after the development of bone metastases are good histologic grade, positive estrogen receptor status, bone disease at initial presentation, a long disease free interval, and increasing age. In addition, patients with disease that remains confined to the skeleton have a better prognosis than those with subsequent visceral involvement. For patients with prostate carcinoma, adverse prognostic features include poor performance status, involvement of the appendicular skeleton and visceral involvement, whereas for patients with multiple myeloma, the levels of serum beta2-microglobulin and lactate dehydrogenase and the immunologic phenotype are the most important factors. These prognostic factors may be useful in planning the rational use of bisphosphonates in the treatment of advanced cancer.