Breast Cancer Research and Treatment

, Volume 121, Issue 2, pp 379–387 | Cite as

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 AiharaEmail author
  • Yuichi Takatsuka
  • Shozo Ohsumi
  • Kenjiro Aogi
  • Yasuo Hozumi
  • Shigeru Imoto
  • Hirofumi Mukai
  • Hiroji Iwata
  • Toru Watanabe
  • Chikako Shimizu
  • Kazuhiko Nakagami
  • Motoshi Tamura
  • Toshikazu Ito
  • Norikazu Masuda
  • Nobuo Ogino
  • Kazufumi Hisamatsu
  • Shoshu Mitsuyama
  • Hajime Abe
  • Shiro Tanaka
  • Takuhiro Yamaguchi
  • Yasuo Ohashi
Clinical trial


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 



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 ( 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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Copyright information

© Springer Science+Business Media, LLC. 2010

Authors and Affiliations

  • Tomohiko Aihara
    • 1
    Email author
  • Yuichi Takatsuka
    • 2
  • Shozo Ohsumi
    • 3
  • Kenjiro Aogi
    • 3
  • Yasuo Hozumi
    • 4
  • Shigeru Imoto
    • 5
  • Hirofumi Mukai
    • 6
  • Hiroji Iwata
    • 7
  • Toru Watanabe
    • 8
  • Chikako Shimizu
    • 9
  • Kazuhiko Nakagami
    • 10
  • Motoshi Tamura
    • 11
  • Toshikazu Ito
    • 12
  • Norikazu Masuda
    • 13
  • Nobuo Ogino
    • 14
  • Kazufumi Hisamatsu
    • 15
  • Shoshu Mitsuyama
    • 16
  • Hajime Abe
    • 17
  • Shiro Tanaka
    • 18
  • Takuhiro Yamaguchi
    • 19
  • Yasuo Ohashi
    • 20
  1. 1.Breast Center, Aihara HospitalMinohJapan
  2. 2.Department of Breast SurgeryKansai Rosai HospitalAmagaskiJapan
  3. 3.Department of Breast OncologyNational Hospital Organization Shikoku Cancer CenterMatsuyamaJapan
  4. 4.Department of Breast and General SurgeryJichi Medical UniversityShimotsukeJapan
  5. 5.Department of Breast Surgery, School of MedicineKyorin UniversityMitakaJapan
  6. 6.Division of Oncology and HematologyNational Cancer Center Hospital EastKashiwaJapan
  7. 7.Department of Breast OncologyAichi Cancer Center HospitalNagoyaJapan
  8. 8.Department of Medical OncologyHamamatsu Oncology CenterHamamatsuJapan
  9. 9.Division of Breast and Medical OncologyNational Cancer Center HospitalTokyoJapan
  10. 10.Department of Breast SurgeryShizuoka General HospitalShizuokaJapan
  11. 11.Department of SurgeryKKR Sapporo Medical CenterSapporoJapan
  12. 12.Department of SurgeryRinku General Medical CenterIzumiotsuJapan
  13. 13.Department of Surgery, Breast OncologyOsaka National HospitalOsakaJapan
  14. 14.Department of SurgeryTondabayashi HospitalTondabayashiJapan
  15. 15.Department of SurgeryHiroshima City Asa HospitalHiroshimaJapan
  16. 16.Department of SurgeryKitakyushu Municipal Medical CenterKitakyushuJapan
  17. 17.Department of SurgeryShiga University of Medical ScienceOtsuJapan
  18. 18.Division of Clinical Trial Design & Management, Translational Research CenterKyoto UniversityKyotoJapan
  19. 19.Department of Clinical Trial Data Management, Graduate School of MedicineUniversity of TokyoTokyoJapan
  20. 20.Department of Biostatistics, School of Public HealthUniversity of TokyoTokyoJapan

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