Endocrine Therapy plus Zoledronic Acid in Premenopausal Breast Cancer

被引：836

作者：

Gnant, Michael ^{[1
]}

Mlineritsch, Brigitte ^{[4
]}

Schippinger, Walter ^{[5
]}

Luschin-Ebengreuth, Gero ^{[5
]}

Poestlberger, Sabine ^{[6
]}

Menzel, Christian ^{[4
]}

Jakesz, Raimund ^{[1
]}

Seifert, Michael ^{[1
]}

Hubalek, Michael ^{[8
]}

Bjelic-Radisic, Vesna ^{[5
]}

Samonigg, Hellmut ^{[5
]}

Tausch, Christoph ^{[6
]}

Eidtmann, Holger ^{[10
]}

Steger, Guenther ^{[1
]}

Kwasny, Werner ^{[9
]}

Dubsky, Peter ^{[1
]}

Fridrik, Michael ^{[7
]}

Fitzal, Florian ^{[1
]}

Stierer, Michael ^{[2
]}

Rucklinger, Ernst ^{[3
]}

Greil, Richard ^{[4
]}

机构：

[1] Med Univ Vienna, A-1090 Vienna, Austria

[2] Hanusch Hosp, Vienna, Austria

[3] Austrian Breast & Colorectal Canc Study Grp, Vienna, Austria

[4] Paracelsus Med Univ Salzburg, Salzburg, Austria

[5] Med Univ Graz, Graz, Austria

[6] Hosp Sisters Mercy, Linz, Austria

[7] Gen Hosp Linz, Linz, Austria

[8] Med Univ Innsbruck, Innsbruck, Austria

[9] Wiener Neustadt Gen Hosp, Wiener Neustadt, Austria

[10] Univ Schleswig Holstein, Kiel, Germany

来源：

NEW ENGLAND JOURNAL OF MEDICINE | 2009年 / 360卷 / 07期

关键词：

BISPHOSPHONATE-ASSOCIATED OSTEONECROSIS; DELTA T-CELLS; POSTMENOPAUSAL WOMEN; ADJUVANT THERAPY; AUSTRIAN BREAST; BONE LOSS; SOLID TUMORS; TAMOXIFEN; METASTASES; RECEPTOR;

D O I：

10.1056/NEJMoa0806285

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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 endocrineresponsive 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.).

引用

页码：679 / 691

页数：13

共 52 条

[1]

AFT R, 2008, J CLIN ONCOL S, V26, pS46

[2] NEW LOOK AT STATISTICAL-MODEL IDENTIFICATION [J].