Editorial comment on ‘Effects of neoadjuvant chemotherapy with or without zoledronic acid on pathological response: A meta-analysis of randomised trials’

Abstract

In this issue of the European Journal of Cancer, Kroep et al. present their meta-analysis of randomised trials of adding zoledronic acid (ZOL) to neoadjuvant therapy in breast cancer [1]. In their well written paper, they have pooled the individual patient data of 750 patients from four randomised clinical trials. For some, the overall result may be disappointing: In essence, the addition of ZOL overall did not increase complete pathological remission (pCR), which is viewed as the surrogate parameter of choice in the neoadjuvant treatment of breast cancer. Interestingly, however the addition of the bisphosphonate nearly doubled pCR rates in the subgroup of postmenopausal patients, a striking parallelism to the differential menopausal effect of adjuvant bisphosphonate therapy [2]. While it may be considered unlikely that neoadjuvant ZOL will become part of routine clinical practice, this paper raises interesting scientific questions: What is the mechanism of action? And why is there an activity signal in postmenopausal patients only? In any case, the long and winding road of bone-targeted therapy in breast cancer with respect to outcome benefit is enriched with another interesting facet.