Delay in progression of bone metastases in breast cancer patients treated with intravenous pamidronate: results from a multinational randomized controlled trial. The Aredia Multinational Cooperative Group.

Conte, Pierfranco; Latreille, Jean; Mauriac, L.; Calabresi, F.; Santos, Rejane Barbosa; Campos, David; Bonneterre, Jacques; Francini, Guido; Ford, John M.

doi:10.1200/jco.1996.14.9.2552

Cited by 258 publications

(102 citation statements)

References 19 publications

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“…The bisphosphonates, notably intravenous pamidronate (Purohit survival of 2.1 years et al, 1994;Conte et al, 1996;Hortobagyi et al, 1996) and to a lesser 0.001, Figure 5). This extent oral clodronate (Paterson et al, 1993), have been shown to patients subsequently relieve pain, reduce analgesic consumption and improve mobility.…”

Section: Discussion Chi= 1918mentioning

confidence: 99%

Clinical course and prognostic factors following bone recurrence from breast cancer

Coleman

Smith²,

Rubens³

1998

Br J Cancer

255

153

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Summary Three hundred and sixty-seven women presenting to the Breast Unit at Guy's Hospital between 1975 and 1990 whose first distant metastasis was in the skeleton were identified and the influence of a number of patient and tumour characteristics on the development and subsequent prognosis of bone metastases was assessed.One hundred and thirty-nine women had disease that remained clinically confined to the skeleton. They were more likely to be older, with lobular carcinoma and to have presented initially with little or no axillary lymph node involvement. The 228 women who subsequently developed disease at extra-osseus sites were more likely to have poorly differentiated ductal tumours and heavy lymph node involvement at primary diagnosis.On multivariate analysis, the clinical and pathological factors of greatest prognostic importance for survival after the development of bone metastases were histological grade (P = < 0.0001), oestrogen receptor status (P = < 0.0001), bone disease at initial presentation (P= < 0.0001), disease-free interval (P= 0.002) and age (P= 0.006).To enable a rational cost-effective use of bisphosphonates in metastatic bone disease, selection of patients with relatively indolent, bone-only disease for bisphosphonate therapy (as defined in this study) should be compared with the current licensed recommendation of unselected treatment for all patients with lytic bone metastases.Bone metastases are frequent in advanced breast cancer and often contribute to the cause of death. Like breast cancer affecting other organs, metastatic bone disease has an extremely variable prognosis. The median survival is 2 years with 20% of patients remaining alive for 5 years after first recurrence in bone (Coleman and Rubens, 1987). In addition, a significant proportion of patients appear clinically to have disease confined to the skeleton, and these women die of the complications of metastatic bone disease, namely immobility, pathological fractures, hypercalcaemia of malignancy and bone marrow failure, with no evidence clinically of involvement at other metastatic sites.With the development of bisphosphonates as specific treatments for metastatic bone disease (Body et al, 1996), there is increased interest in identifying those patients who are most likely to benefit from bisphosphonate treatment. In addition, if prophylactic use of bisphosphonates proves able to influence the development of bone metastases, it will be important to identify those patients at greatest risk of bone involvement, particularly in isolation from other metastatic disease, so that treatment can be targeted rationally. In this study, we have reviewed the clinical and tumour characteristics of patients developing first recurrence of breast cancer in bone and identified prognostic factors that predict for both survival and/or subsequent spread to other metastatic sites. PATIENTS AND METHODSThree hundred and sixty-seven women presenting to the Breast Unit at Guy's Hospital between 1975 and 1990 whose first distant metastasis was in the s...

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Section: Discussion Chi= 1918mentioning

confidence: 99%

Clinical course and prognostic factors following bone recurrence from breast cancer

Coleman

Smith²,

Rubens³

1998

Br J Cancer

255

153

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“…Randomized trials in breast cancer patients have shown that bisphosphonate therapy in combination with either endocrine therapy or chemotherapy can significantly delay the onset of SREs and also reduce their frequency (25,(30)(31)(32)(33)(34). Moreover, in vitro studies have demonstrated that even though an increase in osteoclastic activity is considered to be the predominant mechanism for bone destruction, breast cancer deposits can directly resorb bone (17).…”

Section: Discussionmentioning

confidence: 99%

Examination of the mechanisms of osteolysis in patients with metastatic breast cancer

Clemons¹

2009

Oncol Rep

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Abstract. The benefits of bisphosphonates (BPs) in reducing skeletal-related events (SREs) in patients with bone metastases has mainly been attributed to their potent osteoclast inhibiting effect. However, despite the use of modern systemic anticancer therapy including potent BPs, many patients with bone metastases continue to have SREs. An improved understanding of the fundamental mechanisms of bone destruction allows for further development of appropriate targeted treatments. In this study, archival paraffin-embedded bone metastases specimens from patients with metastatic breast cancer were examined for the presence of osteoclasts, expression of the receptor activator of nuclear factor κB (RANK), RANK Ligand (RANKL), osteoprotegerin (OPG) and vascular endothelial growth factor (VEGF). Histological specimens were available for primary breast cancer, lymph node metastases, normal breast and normal bone tissues for comparison. Bone metastasis specimens were available for 20 BP naïve patients and two BP-treated patients. Osteoclasts were significantly increased in the bone metastases of the BP naïve group compared to normal bone. No osteoclasts were detected in the BP-treated group. RANKL was predominantly expressed in osteoblasts and in the stromal elements of metastatic tissue. Conversely, RANK was present in osteoclasts of bone metastases and normal bone, as well as in tumor cells of metastatic lymph nodes and bone metastases. VEGF was strongly expressed in the control bone and bone metastases regardless of BP treatment. In summary, osteoclasts may not be the singular obligatory factor for osteolysis in bone metastases. An increased expression of RANKL in stromal tissue surrounding bone metastases, RANK in osteoclasts and VEGF may serve as future targeted therapies possibly in conjunction with bisphosphonates. The mechanisms for osteoclast expression and the expression of RANKL, RANK, OPG and VEGF merit further prospective analysis, particularly in the context of BP treatment and progressive bone metastases. IntroductionBreast cancer continues to be the most commonly diagnosed cancer in women in the developed world (1). Bone metastases are the most common site of metastatic recurrence (2) and are a major cause of morbidity for patients. Complications resulting from bone metastases include pain, reduced mobility and a reduced quality of life. In addition, patients are at a considerable risk of, so-called skeletal related events (SREs) such as the requirement for surgery and/or radiotherapy, pathological fractures, spinal cord compression and hypercalcaemia (3). Characteristically, patients with bone as the predominant site of metastatic spread tend to have a protracted disease course when compared to those patients with visceral metastases (4). Furthermore, patients with the disease confined to the skeleton have been found to be most likely to develop skeletal-related complications and hence derive the most benefit from treatment with bone-specific therapies (5).Bone resorption is dependent on a cytokine known a...

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“…Indeed, four placebo-controlled trials (n ϭ 1,453) concluded that i.v. pamidronate (45-90 mg 3-4 weekly) results in a significantly longer time (12.7 versus 7.0 months; p Ͻ .001) to the occurrence of the first SRE (HR, 0.77; 95% CI, 0.69 -0.87), lower incidence of SREs (53% versus 68%; p Ͻ .001), and longer time to progression of bone lesions (8.3 versus 5.6 months; p ϭ .02) [21,[23][24][25][26][27]. Moreover, evidence from a head-to-head comparison suggests its superiority over clodronate in both controlling symptoms and suppressing bone resorption [28].…”

Section: Breast Cancermentioning

confidence: 99%

Bisphosphonates in Oncology: Rising Stars or Fallen Heroes

Wyngaert

Huizing²,

Fossion

et al. 2009

The Oncologist

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The introduction of bisphosphonates in oncology has dramatically changed the management of patients with metastatic bone disease. In this manuscript, we thoroughly scrutinize the available body of clinical trials supporting the use of bisphosphonates in this setting and review new and ongoing research. Additionally, we summarize the data showing the benefits of bisphosphonate use in the prevention of treatment-induced bone loss and the intriguing emerging evidence on the antitumor potential of some of these agents when used in the adjuvant setting. Finally, we address the need for a careful consideration of potential benefits of bisphosphonate therapy and the risk for osteonecrosis of the jaw, a recently recognized late-toxicity of their use. The Oncologist 2009;14:181-191

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Delay in progression of bone metastases in breast cancer patients treated with intravenous pamidronate: results from a multinational randomized controlled trial. The Aredia Multinational Cooperative Group.

Cited by 258 publications

References 19 publications

Clinical course and prognostic factors following bone recurrence from breast cancer

Clinical course and prognostic factors following bone recurrence from breast cancer

Examination of the mechanisms of osteolysis in patients with metastatic breast cancer

Bisphosphonates in Oncology: Rising Stars or Fallen Heroes

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