NEOZOTAC: Efficacy results from a phase III randomized trial with neoadjuvant chemotherapy (TAC) with or without zoledronic acid for patients with HER2-negative large resectable or stage II or III breast cancer (BC)-A Dutch Breast Cancer Trialists' Group (BOOG) study

1028 Background: The role of bisphosphonates when added to the neoadjuvant treatment of BC in enhancing the efficacy of therapy is still unknown. Methods: NEOZOTAC is a national, multicenter, randomized study comparing the efficacy of TAC (docetaxel, Adriamycin and cyclophosphamide i.v.) CT followed by G-CSF on day 2 with or without ZA 4 mg i.v. ,q 3 weeks in patients (pts) with stage II/III, measurable, HER2-negative BC and absence of prior bisphosphonate usage. The primary endpoint is the pathologic complete response (pCR) rate in the resection specimen and positive lymph nodes. 228 pts are needed to show an improvement of the pCR rates from 17% to 34% in the experimental arm using a 5% significance level based on the two-sided Fisher’s exact test with a power of 80%. Randomization was done by using the Pocock’s minimisation technique stratified by cT, cN and estrogen receptor status. pCR rate was analyzed using the Cochran-Mantel-Haenszel test, adjusting for the stratification factors. Analysis was based on intent-to-treat. An unplanned subgroup analysis of postmenopausal women (PMW; FSH >20 and estradiol