Phase III randomized adjuvant study of tamoxifen alone versus sequential tamoxifen and anastrozole in Japanese postmenopausal women with hormone-responsive breast cancer: N-SAS BC03 study
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Clinical trials conducted in Western countries have shown that aromatase inhibitors are associated with better disease-free survival (DFS) than tamoxifen in postmenopausal early breast cancer. Because pharmacogenetic differences in drug-metabolizing genes may cause ethnic differences, assessment of the efficacy and tolerability of aromatase inhibitors in non-white women is warranted. This open-label, randomized clinical trial included 706 postmenopausal Japanese women with hormone-receptor-positive breast cancer, who had received tamoxifen for 1 to 4 years as adjuvant therapy. This study was closed early after entry of ~28% of the initially planned patients. They were randomly assigned to either switch to anastrozole or to continue tamoxifen for total treatment duration of 5 years. Primary endpoints were DFS and adverse events. At a median follow-up of 42 months, the unadjusted hazard ratio was 0.69 (95% confidence interval, 0.42–1.14; P = 0.14) for DFS and 0.54 (95% CI, 0.29–1.02; P = 0.06) for relapse-free survival (RFS), both in favor of anastrozole. The incidence of thromboembolic events in the tamoxifen group and bone fractures in the anastrozole group was not excessively high. Switching from tamoxifen to anastrozole was likely to decrease disease recurrence in postmenopausal Japanese breast cancer patients. Ethnic differences in major adverse events may be attributable to a low baseline risk of these events in Japanese.
KeywordsAdjuvant therapy Anastrozole Breast cancer Ethnic difference Hormonal therapy Tamoxifen
We are indebted to all women who participated in the study. We thank all physicians contributing to this trial. We thank Mizuki Yamauchi and Yumiko Nomura for data management, and Hitoshi Masuda for his editorial assistance. This study was funded by Comprehensive Support Project for Oncology Research (CSPOR) of Public Health Research Foundation. The corporate and individual sponsors of this study are listed on the CSPOR website (http://www.csp.or.jp/cspor/kyousan_e.html). The pharmaceutical manufacturer/distributor who had provided financial contribution as a corporate sponsor took no part in this study other than providing information relevant to proper use of the study drugs. All decisions concerning the planning, implementation and publication of this study were made by the executive committee of this study.
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