LBA4 Background: Zoledronic acid (ZOL) has demonstrated antitumor and antimetastatic activity in preclinical and early clinical studies. The Austrian Breast and Colorectal Cancer Study Group Trial 12 (ABCSG-12) examined the efficacy of ovarian suppression using the gonadotropin-releasing hormone analogue goserelin in combination with anastrozole (ANA) or tamoxifen (TAM) ± ZOL in premenopausal women with endocrine-responsive breast cancer (BC). Methods: 1801 premenopausal women with endocrine-responsive BC were randomized to goserelin (3.6 mg q 28 d SC) and TAM (20 mg/d PO) ± ZOL (4 mg IV q 6 mo) or goserelin and ANA (1 mg/d PO) ± ZOL for 3 yr. Primary endpoint was disease-free survival (DFS) for both the comparison of TAM vs ANA and ZOL vs no ZOL, respectively. Relapse-free survival (RFS) and overall survival (OS) were secondary endpoints. Exploratory endpoints included bone-metastases-free survival and safety. Results: With median follow-up of 60 mo (March 31, 2008), 137 (7.6%) DFS events and 42 (2.3%) d...