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Previous Volume 360:679-691 February 12, 2009 Number 7 Next

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ABSTRACT

Background Ovarian suppression plus tamoxifen is a standard adjuvant treatment in premenopausal women with endocrine-responsive breast cancer. Aromatase inhibitors are superior to tamoxifen in postmenopausal patients, and preclinical data suggest that zoledronic acid has antitumor properties.

Methods We examined the effect of adding zoledronic acid to a combination of either goserelin and tamoxifen or goserelin and anastrozole in premenopausal women with endocrine-responsive early breast cancer. We randomly assigned 1803 patients to receive goserelin (3.6 mg given subcutaneously every 28 days) plus tamoxifen (20 mg per day given orally) or anastrozole (1 mg per day given orally) with or without zoledronic acid (4 mg given intravenously every 6 months) for 3 years. The primary end point was disease-free survival; recurrence-free survival and overall survival were secondary end points.

Results After a median follow-up of 47.8 months, 137 events had occurred, with disease-free survival rates of 92.8% in the tamoxifen group, 92.0% in the anastrozole group, 90.8% in the group that received endocrine therapy alone, and 94.0% in the group that received endocrine therapy with zoledronic acid. There was no significant difference in disease-free survival between the anastrozole and tamoxifen groups (hazard ratio for disease progression in the anastrozole group, 1.10; 95% confidence interval [CI], 0.78 to 1.53; P=0.59). The addition of zoledronic acid to endocrine therapy, as compared with endocrine therapy without zoledronic acid, resulted in an absolute reduction of 3.2 percentage points and a relative reduction of 36% in the risk of disease progression (hazard ratio, 0.64; 95% CI, 0.46 to 0.91; P=0.01); the addition of zoledronic acid did not significantly reduce the risk of death (hazard ratio, 0.60; 95% CI, 0.32 to 1.11; P=0.11). Adverse events were consistent with known drug-safety profiles.

Conclusions The addition of zoledronic acid to adjuvant endocrine therapy improves disease-free survival in premenopausal patients with estrogen-responsive early breast cancer. (ClinicalTrials.gov number, NCT00295646 [ClinicalTrials.gov] .)

Source Information

From the Medical University of Vienna (M.G., R.J., M. Seifert, G.S., P.D., F.F.), Hanusch Hospital (M. Stierer), and the Austrian Breast and Colorectal Cancer Study Group (E.R.) — all in Vienna; Paracelsus Medical University Salzburg, Salzburg (B.M., C.M., R.G.); Medical University of Graz, Graz (W.S., G.L.-E., V.B.-R., H.S.); Hospital of the Sisters of Mercy (S.P., C.T.) and General Hospital Linz (M.F.) — both in Linz; Medical University of Innsbruck, Innsbruck (M.H.); and Wiener Neustadt Hospital, Wiener Neustadt (W.K.) — all in Austria; and the University of Schleswig-Holstein, Kiel, Germany (H.E.).

This article (10.1056/NEJMoa0806285) was updated on May 27, 2009, at NEJM.org.

Address reprint requests to Dr. Gnant at the Medical University of Vienna, Währinger Gürtel 18-20, A-1090 Vienna, Austria, or at michael.gnant{at}meduniwien.ac.at.

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