Adjuvant pamidronate (PMT) therapy for the prevention of bone metastasis in breast cancer (BC) patients (pts) with four or more positive nodes

Abstract

530 Background: In BC pts, bone is the most frequent site of distant metastasis. The pathogenesis of bone metastasis is thought that BC cells produce osteoclast activating factors which induce osteoclast resorption of bone, leading to the development of lytic bone disease. Bisphosphonates (BPs) demonstrate highly effective inhibition of osteoclast bone resorption and have beneficial effects on bone metastases. Because of their mechanism, BPs are expected to prevent the development of bone metastases. PMT is a potent inhibitor of osteoclast activity. We examined whether adjuvant PMT therapy could prevent or delay the development of bone metastases in BC pts at high risk for bone metastases. Methods: Between 1997 and 2001, 90 pts with primary BC and four or more positive nodes were assigned by patients preference to receive PMT therapy (PMT 45mg iv every 2 weeks times 4 cycle; n=33) or control (C) (no therapy; n=57). All pts underwent surgical treatment and the type of adjuvant systemic therapy was based on the protocols of each center. The clinicopathological characteristics of the pts (age, tumor size, nodal status, menopausal status, hormonal status, type of chemotherapy ) were well balanced. The median follow-up period was 5.4 years. Results: Bone metastases were detected in 4 pts (12.1%) in the PMT group and in 22 pts (38.6%) in the C group (p=.008). Distant metastases (36.4% vs 52.6%, p=.136) and visceral and soft tissue metastases (30.3% vs 45.6%, p=.153) were detected lower in the PMT group compared with the C group, but no statistically significant. Six pts (18.2%) in the PMT group and 15 pts (26.3%) in the C group died (p=0.379). Overall survival and disease-free survival rates were equal in the both groups. Bone metastasis free survival was significantly higher in the PMT group compared to the C group (85.0% vs 63.8% at 5 years, p=.035). Conclusion: In the PMT group, the incidence of bone metastases was significantly reduced and bone metastasis free survival was significantly higher. We conclude that adjuvant PMT therapy significantly reduced the development of bone metastases in BC pts with four or more positive nodes. No significant financial relationships to disclose.