Clinical trial

Breast Cancer Research and Treatment

, Volume 121, Issue 2, pp 379-387

First online:

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

  • Tomohiko AiharaAffiliated withBreast Center, Aihara Hospital Email author 
  • , Yuichi TakatsukaAffiliated withDepartment of Breast Surgery, Kansai Rosai Hospital
  • , Shozo OhsumiAffiliated withDepartment of Breast Oncology, National Hospital Organization Shikoku Cancer Center
  • , Kenjiro AogiAffiliated withDepartment of Breast Oncology, National Hospital Organization Shikoku Cancer Center
  • , Yasuo HozumiAffiliated withDepartment of Breast and General Surgery, Jichi Medical University
  • , Shigeru ImotoAffiliated withDepartment of Breast Surgery, School of Medicine, Kyorin University
  • , Hirofumi MukaiAffiliated withDivision of Oncology and Hematology, National Cancer Center Hospital East
  • , Hiroji IwataAffiliated withDepartment of Breast Oncology, Aichi Cancer Center Hospital
  • , Toru WatanabeAffiliated withDepartment of Medical Oncology, Hamamatsu Oncology Center
    • , Chikako ShimizuAffiliated withDivision of Breast and Medical Oncology, National Cancer Center Hospital
    • , Kazuhiko NakagamiAffiliated withDepartment of Breast Surgery, Shizuoka General Hospital
    • , Motoshi TamuraAffiliated withDepartment of Surgery, KKR Sapporo Medical Center
    • , Toshikazu ItoAffiliated withDepartment of Surgery, Rinku General Medical Center
    • , Norikazu MasudaAffiliated withDepartment of Surgery, Breast Oncology, Osaka National Hospital
    • , Nobuo OginoAffiliated withDepartment of Surgery, Tondabayashi Hospital
    • , Kazufumi HisamatsuAffiliated withDepartment of Surgery, Hiroshima City Asa Hospital
    • , Shoshu MitsuyamaAffiliated withDepartment of Surgery, Kitakyushu Municipal Medical Center
    • , Hajime AbeAffiliated withDepartment of Surgery, Shiga University of Medical Science
    • , Shiro TanakaAffiliated withDivision of Clinical Trial Design & Management, Translational Research Center, Kyoto University
    • , Takuhiro YamaguchiAffiliated withDepartment of Clinical Trial Data Management, Graduate School of Medicine, University of Tokyo
    • , Yasuo OhashiAffiliated withDepartment of Biostatistics, School of Public Health, University of Tokyo

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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.


Adjuvant therapy Anastrozole Breast cancer Ethnic difference Hormonal therapy Tamoxifen