Analysis of the Austrian Breast and Colorectal Cancer Study Group Trial 12 (ABCSG-12) at 48 months' follow-up showed That addition under or zoledronic acid to adjuvant endocrine therapy significantly improved disease-free survival. We have now assessed long-term clinical efficacy Including disease-free survival and disease outcomes in patient receiving tamoxifen or anastrozole with or without zoledronic acid.

ABSCG-12 is a randomized, controlled, open-label, two-by-two factorial, multicentre trial in 1803 premenopausal women with endocrine-receptor-positive early-stage (stage I-II) breast cancer receiving goserelin (3.6 mg Every 28 days), Comparing the efficacy and safety of anastrozole (1 mg per day) or tamoxifen (20 mg per day) with or without zoledronic acid (4 mg everytime 6 months) for 3 years. Randomisation (1:1:1:1 ratio) was based on the computerized and Pocock and Simon minimization method to balance the four treatment arms across eight Prognostic variables (age, neoadjuvant chemotherapy, Pathological tumor stage, lymph node involvement, type of surgery or locoregional therapy, complete axillary dissection, intraoperative radiation therapy, and Geographical region). Treatment allocation was not masked. The primary endpoint was disease-free survival (defined as disease Recurrence or death) and analysis was by intention to treat. This trial is registered with ClinicalTrials.gov , number NCT00295646 ; follow-up is ongoing.

At a median follow-up of 62 months (range 0-114 • 4 months), More Than 2 years after treatment completion, 186 disease-free survival was bone Reported events (53 events in 450 patients on tamoxifen alone, 57 in 453 patients on anastrozole alone, 36 in 450 patients on tamoxifen plus zoledronic acid, and 40 in 450 patients on anastrozole plus zoledronic acid). Zoledronic acid Reduced risk of disease-free survival events overall (HR 0.68, 95% CI 0.51 -0 ° 91, p = 0.009), although the difference was not significant in the tamoxifen (HR 0.67, 95% CI 0.44 -1 ° 03, p = 0.067) and anastrozole arm (HR 0.68, 95% CI 0.45 -1 ° 02, p = 0.061) assessed Separately. Zoledronic acid did not significantly affect risk of death (30 deaths with zoledronic acid vs 43 deaths without, HR 0.67, 95% CI 0.41 -1 · 07, p = 0.09). There was no difference in disease-free survival Between Patients on tamoxifen alone versus anastrozole alone (HR 1.08, 95% CI 0.81 -1 · 44, p = 0.591), but overall survival was worse with anastrozole with Than tamoxifen (46 vs. 27 deaths: HR 1.75, 95% CI 1.08 -2 ° 83, p = 0.02). Treatments Were Generally well tolerated, with no reports of renal failure or osteonecrosis of the jaw. Bone pain was Reported in 601 patients (33%, 349 patients on zoledronic acid vs 252 not on the drug), fatigue in 361 (20%, 192 vs. 169), headache in 280 (16%, 147 vs. 133), and arthralgia in 266 (15%, 145 vs. 121).

Addition of zoledronic acid improved disease-free survival in the anastrozole or tamoxifen takingcare patiënten. There was no difference in disease-free survival Between Patients receiving anastrozole and tamoxifen overall, but Those on anastrozole alone had inferior overall survival. These data show persistent benefits with zoledronic acid and ITS support to adjuvant endocrine therapy in addition under premenopausal patients with early-stage breast cancer.