Adjuvant zoledronic acid therapy for patients with early stage breast cancer: an updated systematic review and meta-analysis

Abstract

BackgroundZoledronic acid is a potent inhibitor of osteoclast-mediated bone resorption and has been widely used in bone metastasis malignancies and postmenopausal osteoporosis as a preventive therapy against skeletal-related events. The purpose of this study was to evaluate the clinical outcome of zoledronic acid as an adjuvant therapy for patients with early stage breast cancer.Patients and methodsEntries in the PubMed and EMBASE databases up to 12 July 2013 were systematically reviewed. Online abstracts from the proceedings of the Annual Meetings of the American Society of Clinical Oncology (ASCO) (1992–2013) and the San Antonio Breast Cancer Symposium (SABCS) (2004–2013) were also reviewed. Primary endpoints included overall survival (OS) and disease-free survival (DFS), while secondary endpoints included bone metastasis-free survival (BMFS), distant metastasis-free survival (DMFS), and fracture-free rate (FFR).ResultsA total of eight studies including 3,866 subjects and 3,864 controls met our search criteria and were evaluated. The use of zoledronic acid was found to improve OS (relative risk (RR), 0.88; 95% confidence interval (CI), 0.77–1.01; p-value = 0.06) and DMFS (RR, 0.77; 95% CI, 0.60–1.00; p-value = 0.05). Furthermore, statistically significant benefits were associated with BMFS (RR, 0.81; 95% CI, 0.66–0.99; p-value = 0.04) and FFRs (RR, 0.75; 95% CI, 0.61–0.92; p-value = 0.007). In contrast, there was no significant difference in DFS with the application of zoledronic acid (RR, 0.88; 95% CI, 0.72–1.09; p-value = 0.24). Sensitivity analysis further identified the improvement of 5-year OS for the adjuvant zoledronic acid therapy in early stage breast cancer patients (RR, 0.86; 95% CI, 0.75–0.99; p-value = 0.03), while a borderline statistically significant benefit was observed for 5-year DFS (RR, 0.90; 95% CI, 0.81–1.00; p-value = 0.06).ConclusionZoledronic acid as an adjuvant therapy appears to improve the 5-year OS rate for early stage breast cancer patients, and was associated with a protective effect for the bone metastases and fractures evaluated in more than 7,000 patients. However, further research is needed to confirm our findings, and sub-group analyses according to menopause status or hormone status may provide further insight.

Risk of hospitalisation and death due to bone fractures after breast cancer: a registry-based cohort study

“…Bisphosphonates, a class of drugs commonly administered to prevent bone loss and treat osteoporosis, have been widely used to prevent disease recurrence and mortality in breast cancer metastatic patients (Hillner et al , 2003; van Poznak et al , 2011; Wong et al , 2012). Recently, a growing body of evidence is also supporting their use in women with early breast cancer to improve prognosis (Gnant et al , 2009; Coleman et al , 2013; He et al , 2013; Early Breast Cancer Trialists' Collaborative Group (EBCTCG), 2015). In addition, the use of adjuvant denosumab has been found to reduce the risk of bone fractures in postmenopausal women treated with aromatase inhibitors (Gnant et al , 2015).…”

Role of zoledronic acid in oncolytic virotherapy: Promotion of antitumor effect and prevention of bone destruction

“…Zoledronic acid (ZOL) is a third‐generation bisphosphonate, which can inhibit bone destruction in patients with metastatic bone tumors or multiple myeloma . Moreover, ZOL has been shown to exert an antitumor effect against osteosarcoma cells .…”

Cost–Utility of Adjuvant Zoledronic Acid in Patients with Breast Cancer and Low Estrogen Levels

“…The only two phase iii trials that considered cancer-specific primary endpoints and compared adjuvant therapy with and without za (abcsg-12 and azure) independently suggested that adjuvant za improves breast cancer outcomes in patients with low circulating estrogen levels secondary to induced or natural menopause 13,14 . Meta-analyses of adjuvant za and adjuvant bisphosphonate trials as a whole appear to confirm the benefit in that subgroup of patients 6,[15][16][17] .…”