Effect of Long-Term Bisphosphonate Treatment on Morbidity Due To Bone Metastases in Breast Cancer Patients

Cleton, F. J.; Holten-Verzantvoort, A.Th. van; Bijvoet, O. L. M.

doi:10.1007/978-3-642-83668-8_7

Cited by 14 publications

(4 citation statements)

References 14 publications

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“…It is already clear from clinical studies that the use of bisphosphonates, potent inhibitors of bone resorption, significantly reduces skeletal morbidity in advanced breast cancer (312)(313)(314)(315)(316)(317)(318)(319)(320)(321)(322)(323). It is already clear from clinical studies that the use of bisphosphonates, potent inhibitors of bone resorption, significantly reduces skeletal morbidity in advanced breast cancer (312)(313)(314)(315)(316)(317)(318)(319)(320)(321)(322)(323).…”

Section: Osteolytic Metastasesmentioning

confidence: 99%

“…All of the available evidence from these studies suggests that drugs that decrease bone resorption, such as the potent bisphosphonates, have a beneficial effect on skeletal complications, including pain and pathological fracture, prevention of hypercalcemia, and improved quality of life. It is apparent from clinical studies that the use of bisphosphonates reduces significant skeletal morbidity in advanced breast cancer (312)(313)(314)(315)(316)(317)(318)(319)(320)(321)(322)(323). However, there may be an added beneficial effect of the bisphosphonates that is even more important.…”

Section: Therapy Of Tumor In Bonementioning

confidence: 99%

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Cancer and Bone*

1998

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Section: Osteolytic Metastasesmentioning

confidence: 99%

Section: Therapy Of Tumor In Bonementioning

confidence: 99%

Cancer and Bone*

1998

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“…Thus, once breast cancer cells arrest in bone, the high concentrations of growth factors and cytokines in the bone microenvironment provide a fertile soil on which the cells A large body of indirect evidence to support the concept that bone is a fertile soil, further enriched by the process of osteoclastic bone resorption, has accumulated in studies using bisphosphonates in the treatment of bone metastases. It is already clear from clinical studies that the use of bisphosphonates, potent inhibitors of bone resorption, significantly reduces skeletal morbidity in advanced breast cancer (312)(313)(314)(315)(316)(317)(318)(319)(320)(321)(322)(323). In a recent multicenter trial that consisted of more than 700 patients with stage IV breast cancer with two or more predominantly lytic lesions, with at least one lesion that was 1 cm or greater in diameter, treatment with pamidronate 90 mg iv every 3-4 weeks for 12 months in conjunction with chemotherapy or hormonal therapy resulted in a significant reduction in skeletal complications and bone pain compared with the control group (321).…”

Section: Local Tumor Syndromes In Bonementioning

confidence: 99%

“…This likely occurs because the bisphosphonates make bone a less favorable environment for the growth of tumor cells by reducing bone turnover and decreasing the supply of local bone-derived growth factors that also act as tumor growth factors in the bone microenvironment. It is apparent from clinical studies that the use of bisphosphonates reduces significant skeletal morbidity in advanced breast cancer (312)(313)(314)(315)(316)(317)(318)(319)(320)(321)(322)(323). These data suggest that drugs that inhibit bone resorption may be useful adjuvant therapy in patients with malignant disease by preventing the growth of tumor cells in the skeleton.…”

Section: Therapy Of Tumor In Bonementioning

confidence: 99%

Cancer and Bone

Guise¹

2013

Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism

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Effect of the bisphosphonate risedronate on bone metastases in a rat mammary adenocarcinoma model system

Hall

Stoica

1994

Journal of Bone and Mineral Research

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Risedronate (NE-58095) is a third-generation bisphosphonate with very potent antiresorptive activity but few toxic effects. The purpose of this work was to evaluate the effect of risedronate treatment on bone metastases produced in a rat breast cancer model. Berlin Druckrey IV rats inoculated with ENU1564 mammary adenocarcinoma cells were treated daily with risedronate or a saline placebo. Survival times, dictated by extraskeletal metastases (lung, heart, and brain), were not affected by risedronate treatment. Risedronate-treated animals had skeletal changes associated with decreased remodeling of bones undergoing endochondral ossification, most prominently affecting the appendicular skeleton. Despite the skeletal alterations induced by the treatment, the distribution of bone metastases throughout the surveyed skeletal sites was similar for treated and untreated animals. Bone metastases were enumerated in histologic sections of distal femur, spine, and skull. Tumor size was estimated from area measurements obtained from histologic lesions in distal femoral metaphyses and vertebral bodies. A greater number of treated rats had no bone metastases in any of the examined sections (30 versus 16.1% of untreated rats). Multiple bone metastases were observed less frequently in treated rats (33.3 versus 71% of untreated rats). Treated rats had fewer observed bone metastases in each examined site than untreated rats (p < or = 0.025). Mean tumor areas in femora and vertebrae were smaller in treated rats (p < or = 0.05), due to the less frequent presence of very large lesions. In untreated animals, osteoclasts appeared to be active at the tumor/bone interface and osseous structures were often completely replaced by expanding tumors. In contrast, metastases in treated animals caused less disruption of skeletal histoarchitecture. The apparent lack of osteoclastic activity and retention of bone within lesions suggested a decreased contribution of osteoclasts to the bone resorptive process. An in vivo immunohistochemical cell proliferation assay failed to reveal differences in the percentage of dividing tumor cells in bone metastatic sites in treated versus untreated animals. The results demonstrate significant effects of risedronate treatment on the incidence and size of observed skeletal metastases in this model.

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Effect of Long-Term Bisphosphonate Treatment on Morbidity Due To Bone Metastases in Breast Cancer Patients

Cited by 14 publications

References 14 publications

Cancer and Bone*

Cancer and Bone*

Cancer and Bone

Effect of the bisphosphonate risedronate on bone metastases in a rat mammary adenocarcinoma model system

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