Research progress in antitumor effects of zoledronic acid in early breast cancer

Abstract

Adjuvant treatment, which includes chemotherapy and endocrine therapy, for early breast cancer may impair bone density, resulting in bone loss. The third generation bisphosphonate-zoledronic is an anti-resorptive agent that inhibits osteoclast-mediated bone resorption. This drug can be mainly used in the treatment of hypercalcemia caused by bone metastases of the cancer. The Zometa-Femara Adjuvant Synergy Trial revealed that immediate zoledronic acid and endocrine therapy not only prevents bone loss, but also reduces recurrence. The Austrian Breast and Colorectal Cancer Study Group-12 (ABCSG-12) also confirmed that zoledronic acid, when combined with endocrine therapy, could reduce the risk of cancer disease progression and death. Moreover, preclinical studies and clinical trials have demonstrated the synergistic antitumor effects of chemotherapy and zoledronic acid. Neo-adjuvant zoledronic acid to reduce recurrence trials showed that the addition of zoledronic acid to adjuvant chemotherapy significantly reduced the risk of disease progression and death in postmenopausal women more than five years postmenopause at the beginning of the study or over 60 years of age at the baseline. The ABCSG-12 subgroup analysis based on age (≤40 years or >40 years) also showed that zoledronic acid can significantly improve the prognosis in women who were over 40 years at the study entry. These results suggest that zoledronic acid administration in patients with lowered estrogen levels (naturally or as a consequence of adjuvant treatment) easily exerts anti-tumor effects. However, the optimal dose and duration of zoledronic acid requires further studies. More clinical trials should be performed to provide sufficient evidence to support the effectiveness of zoledronic acid in the treatment of early breast cancer.