The effects of neoadjuvant zoledronic acid in breast cancer patients: A meta-analysis of randomized controlled trials

To explore the effects of Zoledronic acid (ZA) in the neoadjuvant setting, we conducted a meta-analysis of randomized controlled trials (RCTs) of neoadjuvant therapy with or without ZA in breast cancer (BC). A systematic literature search was carried out by two reviewers independently on the basis of three electronic databases up to February 2022. Six RCTs with a total of 949 patients, comparing neoadjuvant therapy with or without ZA in BC were included. In the total population, adding ZA to the neoadjuvant setting didn't improved the pathological complete response (pCR) rates (Risk Ratio (RR) = 1.38, 95% CI 0.94-2.03, p = 0.10). However, subgroup analysis revealed that the addition of ZA resulted in an increased pCR rate in postmenopausal women (RR = 2.30, 95% CI 0.93-5.71, p = 0.07) and in patients with triple-negative BC (RR = 2.85, 95% CI 1.01-8.03, p = 0.05), although these results were not statistically significant. Furthermore, the additional ZA did not show benefits on objective response rate, breast-conserving surgery rate or recurrence rate. For mortality, however, the additional ZA resulting in worse outcome compared to the control group (RR = 1.48, 95% CI 1.04-2.10, p = 0.03). Our study suggested that addition of ZA to neoadjuvant therapy didn't improved the pCR rate. Further investigations are warranted in postmenopausal women and patients with triple-negative BC, since these subgroups might benefit from ZA treatment.