Efficacy of Pamidronate in Reducing Skeletal Complications in Patients with Breast Cancer and Lytic Bone Metastases

Hortobágyi, Gabriel N.; Theriault, Richard L.; Porter, Lester; Blayney, Douglas W.; Lipton, Allan; Sinoff, Clive; Wheeler, Helen; Simeone, Joseph F.; Seaman, John J.; Knight, Robert D.; Heffernan, Maika; Reitsma, Dirk J.; Kennedy, Ian; Allan, Simon; Mellars, Kathleen

doi:10.1056/nejm199612123352401

Cited by 944 publications

(488 citation statements)

References 23 publications

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“…Despite antiresorptive therapy, repair of existing lesions is not seen, and progressive disease is associated with new skeletal events. (8)(9)(10)(11)(12)(13) New strategies to reduce skeletal-related events and improve patient outcome are urgently required.…”

Section: Introductionmentioning

confidence: 99%

Inhibiting activin-A signaling stimulates bone formation and prevents cancer-induced bone destruction in vivo

Chantry

Heath

Mulivor

et al. 2010

Journal of Bone and Mineral Research

135

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Cancers that grow in bone, such as myeloma and breast cancer metastases, cause devastating osteolytic bone destruction. These cancers hijack bone remodeling by stimulating osteoclastic bone resorption and suppressing bone formation. Currently, treatment is targeted primarily at blocking bone resorption, but this approach has achieved only limited success. Stimulating osteoblastic bone formation to promote repair is a novel alternative approach. We show that a soluble activin receptor type IIA fusion protein (ActRIIA.muFc) stimulates osteoblastogenesis ( p < .01), promotes bone formation ( p < .01) and increases bone mass in vivo ( p < .001). We show that the development of osteolytic bone lesions in mice bearing murine myeloma cells is caused by both increased resorption ( p < .05) and suppression of bone formation ( p < .01). ActRIIA.muFc treatment stimulates osteoblastogenesis ( p < .01), prevents myeloma-induced suppression of bone formation ( p < .05), blocks the development of osteolytic bone lesions ( p < .05), and increases survival ( p < .05). We also show, in a murine model of breast cancer bone metastasis, that ActRIIA.muFc again prevents bone destruction ( p < .001) and inhibits bone metastases ( p < .05). These findings show that stimulating osteoblastic bone formation with ActRIIA.muFc blocks the formation of osteolytic bone lesions and bone metastases in models of myeloma and breast cancer and paves the way for new approaches to treating this debilitating aspect of cancer. ß

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Section: Introductionmentioning

confidence: 99%

Inhibiting activin-A signaling stimulates bone formation and prevents cancer-induced bone destruction in vivo

Chantry

Heath

Mulivor

et al. 2010

Journal of Bone and Mineral Research

135

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“…Medical therapies include systemic chemotherapy/hormonal therapy and medications specific for spinal metastases, such as steroids, analgesics, and bisphosphonates [6,12,31,34,41]. Bisphosphonates are highly effective in reducing bone pain, hypercalcemia and pathological fractures, and they are frequently used at our institutions [23,30,31]. For patients with localized bone pain that has not responded to systemic therapy and analgesics, external beam irradiation (30 Gy in ten fractions) is the treatment of choice and usually provides good pain relief [29,31,32,40].…”

Section: Discussionmentioning

confidence: 99%

Surgical treatment strategies and outcome in patients with breast cancer metastatic to the spine: a review of 87 patients

et al. 2007

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Aggressive surgical management of spinal metastatic disease can provide improvement of neurological function and significant pain relief. However, there is limited literature analyzing such management as is pertains to individual histopathology of the primary tumor, which may be linked to overall prognosis for the patient. In this study, clinical outcomes were reviewed for patients undergoing spinal surgery for metastatic breast cancer. Respective review was done to identify all patients with breast cancer over an eight-year period at a major cancer center and then to select those with symptomatic spinal metastatic disease who underwent spinal surgery. Pre-and postoperative pain levels (visual analog scale [VAS]), analgesic medication usage, and modifed Frankel grade scores were compared on all patients who underwent surgery. Univariate and multivariate analyses were used to assess risks for complications. A total of 16,977 patients were diagnosed with breast cancer, and 479 patients (2.8%) were diagnosed with spinal metastases from breast cancer. Of these patients, 87 patients (18%) underwent 125 spinal surgeries. Of the 76 patients (87%) who were ambulatory preoperatively, the majority (98%) were still ambulatory.Of the 11 patients (13%) who were nonambulatory preoperatively, four patients were alive at 3 months postoperatively, three of which (75%) regained ambulation. The preoperative median VAS of six was significantly reduced to a median score of two at the time of discharge and at 3, 6, and 12 months postoperatively (P < 0.001 for all time points). A total of 39% of patients experienced complications; 87% were early (within 30 days of surgery), and 13% were late. Early major surgical complications were significantly greater when five or more levels were instrumented. In patients with spinal metastases specifically from breast cancer, aggressive surgical management provides significant pain relief and preservation or improvement of neurological function with an acceptably low rate of complications.

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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%

“…Support for such selection does however require analysis of a larger database of patients, with recording of skeletal events and their subsequent treatment. It is hoped that the recent randomized trials of pamidronate (Hortobagyi et al, 1996;Lipton et al, 1997), which included the collection of data for economic evaluation as well as meticulous recording of skeletal events, will use these data for analysis not only by treatment group but also according to prognostic factors, including those identified in this study, to assess whether the selective use of bisphosphonates improves the cost-effectiveness of this new treatment modality. In addition, and possibly of greater value, might be the ability to specify those patients at most risk of developing serious complications of bone metastases, particularly pathological fracture and hypercalcaemia, but the relevant predictors remain to be identified.…”

Section: Discussion Chi= 1918mentioning

confidence: 99%

Clinical course and prognostic factors following bone recurrence from breast cancer

Coleman

Smith²,

Rubens³

1998

Br J Cancer

257

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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Efficacy of Pamidronate in Reducing Skeletal Complications in Patients with Breast Cancer and Lytic Bone Metastases

Abstract: Monthly infusions of pamidronate as a supplement to chemotherapy can protect against skeletal complications in women with stage IV breast cancer who have osteolytic bone metastases.

Cited by 944 publications

References 23 publications

Inhibiting activin-A signaling stimulates bone formation and prevents cancer-induced bone destruction in vivo

Inhibiting activin-A signaling stimulates bone formation and prevents cancer-induced bone destruction in vivo

Surgical treatment strategies and outcome in patients with breast cancer metastatic to the spine: a review of 87 patients

Clinical course and prognostic factors following bone recurrence from breast cancer

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