Zoledronic acid combined with adjuvant endocrine therapy of tamoxifen versus anastrozol plus ovarian function suppression in premenopausal early breast cancer: final analysis of the Austrian Breast and Colorectal Cancer Study Group Trial 12

Ann Oncol. 2015 Feb;26(2):313-20. doi: 10.1093/annonc/mdu544. Epub 2014 Nov 17.


Background: Zoledronic acid (ZOL) plus adjuvant endocrine therapy significantly improved disease-free survival (DFS) at 48- and 62-month follow-up in the ABCSG-12 trial. We present efficacy results of a final additional analysis after 94.4 months.

Patients and methods: Patients were premenopausal women who had undergone primary surgery for stage I/II estrogen-receptor-positive and/or progesterone-receptor-positive breast cancer with <10 positive lymph nodes, and were scheduled for standard goserelin therapy. All 1803 patients received goserelin (3.6 mg every 28 days) and were randomized to tamoxifen (20 mg/days) or anastrozole (1 mg/days), both with or without ZOL (4 mg every 6 months) for 3 years. The primary end point was DFS; recurrence-free survival and overall survival (OS) were secondary end points.

Results: After 94.4-month median follow-up (range, 0-114 months), relative risks of disease progression [hazard ratio (HR) = 0.77; 95% confidence interval (CI) 0.60-0.99; P = 0.042] and of death (HR = 0.66; 95% CI 0.43-1.02; P = 0.064) are still reduced by ZOL although no longer significant at the predefined significance level. Overall, 251 DFS events and 86 deaths were reported. Absolute risk reductions with ZOL were 3.4% for DFS and 2.2% for OS. There was no DFS difference between tamoxifen alone versus anastrozole alone, but there was a pronounced higher risk of death for anastrozole-treated patients (HR = 1.63; 95% CI 1.05-1.45; P = 0.030). Treatments were generally well tolerated, with no reports of renal failure or osteonecrosis of the jaw.

Conclusion: These final results from ABCSG 12 suggest that twice-yearly ZOL enhances the efficacy of adjuvant endocrine treatment, and this benefit is maintained long-term.

Clinicaltrialsgov: NCT00295646 (http://www.clinicaltrials.gov/ct2/results?term=00295646).

Keywords: LHRH agonists; anastrozol; bisphosphonates; early breast cancer; tamoxifen; zoledronic acid.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anastrozole
  • Antineoplastic Agents, Hormonal / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Bone Density Conservation Agents / administration & dosage*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / mortality
  • Diphosphonates / administration & dosage
  • Disease-Free Survival
  • Female
  • Follow-Up Studies
  • Goserelin / administration & dosage
  • Humans
  • Imidazoles / administration & dosage
  • Kaplan-Meier Estimate
  • Middle Aged
  • Nitriles / administration & dosage
  • Premenopause
  • Tamoxifen / administration & dosage
  • Triazoles / administration & dosage
  • Zoledronic Acid


  • Antineoplastic Agents, Hormonal
  • Bone Density Conservation Agents
  • Diphosphonates
  • Imidazoles
  • Nitriles
  • Triazoles
  • Tamoxifen
  • Goserelin
  • Anastrozole
  • Zoledronic Acid

Associated data

  • ClinicalTrials.gov/NCT00295646