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Anastrozole versus tamoxifen as adjuvant therapy for Japanese postmenopausal patients with hormone-responsive breast cancer: efficacy results of long-term follow-up data from the N-SAS BC 03 trial

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Abstract

Aromatase inhibitors are superior to tamoxifen as adjuvant therapy in postmenopausal patients with hormone-responsive breast cancer. We report the follow-up efficacy results from the N-SAS BC 03 trial (UMIN CTRID: C000000056) where anastrozole was compared with tamoxifen as adjuvant therapy in postmenopausal Japanese patients with hormone-responsive early breast cancer. The full analysis set contained 696 patients (anastrozole arm, n = 345; tamoxifen arm, n = 351). The log-rank test was used to compare the two groups in terms of disease-free survival (DFS) and relapse-free survival (RFS); Kaplan–Meier estimates were calculated. The treatment effects were estimated by Cox’s proportional hazards model. To examine time-varying effect of hazard ratios, we estimated time-varying hazard ratios at time t [HR(t)] using data from time t up to 12 months. After a median follow-up of 98.5 months, hazard ratios (95 % CIs) were 0.90 (0.65–1.24; log-rank p = 0.526) for DFS and 0.83 (0.56–1.23; log-rank p = 0.344) for RFS. Hazard ratios (95 % CIs) for DFS and RFS up to 36 months were 0.69 (0.40–1.17) and 0.54 (0.27–1.06) and those after 36 months were 1.06 (0.70–1.59) and 1.05 (0.64–1.73), respectively. Time-varying hazard ratios for both DFS and RFS showed that hazard ratios were initially in favor of anastrozole and approached 1.0 at around 36 months. Superior efficacy of anastrozole to tamoxifen suggested by the initial analysis was not confirmed in the present analysis after a long-term follow-up period. Advantage of anastrozole was the greatest immediately after switching from tamoxifen and then decreased thereafter.

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References

  1. Cuzick J, Sestak I, Baum M, Buzdar A, Howell A, Dowsett M, Forbes JF (2010) Effect of anastrozole and tamoxifen as adjuvant treatment for early-stage breast cancer: 10-year analysis of the ATAC trial. Lancet Oncol 11:1135–1141

    Article  CAS  PubMed  Google Scholar 

  2. Regan MM, Neven P, Giobbie-Hurder A, Goldhirsch A, Ejlertsen B, Mauriac L, Forbes JF, Smith I, Láng I, Wardley A, Rabaglio M, Price KN, Gelber RD, Coates AS, Thürlimann B (2011) Assessment of letrozole and tamoxifen alone and in sequence for postmenopausal women with steroid hormone receptor-positive breast cancer: the BIG 1-98 randomised clinical trial at 8·1 years median follow-up. Lancet Oncol 12:1101–1108

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  3. van de Velde CJ, Rea D, Seynaeve C, Putter H, Hasenburg A, Vannetzel JM, Paridaens R, Markopoulos C, Hozumi Y, Hille ET, Kieback DG, Asmar L, Smeets J, Nortier JW, Hadji P, Bartlett JM, Jones SE (2011) Adjuvant tamoxifen and exemestane in early breast cancer (TEAM): a randomised phase 3 trial. Lancet 377:321–331

    Article  PubMed  Google Scholar 

  4. Boccardo F, Guglielmini P, Bordonaro R, Fini A, Massidda B, Porpiglia M, Roagna R, Serra P, Orzalesi L, Ucci G, Rubagotti A (2013) Switching to anastrozole versus continued tamoxifen treatment of early breast cancer: long term results of the Italian Tamoxifen Anastrozole trial. Eur J Cancer 49:1546–1554

    Article  CAS  PubMed  Google Scholar 

  5. Kaufmann M, Jonat W, Hilfrich J, Eidtmann H, Gademann G, Zuna I, von Minckwitz G (2007) Improved overall survival in postmenopausal women with early breast cancer after anastrozole initiated after treatment with tamoxifen compared with continued tamoxifen: the ARNO 95 Study. J Clin Oncol 25:2664–2670

    Article  CAS  PubMed  Google Scholar 

  6. Dubsky PC, Jakesz R, Mlineritsch B, Pöstlberger S, Samonigg H, Kwasny W, Tausch C, Stöger H, Haider K, Fitzal F, Singer CF, Stierer M, Sevelda P, Luschin-Ebengreuth G, Taucher S, Rudas M, Bartsch R, Steger GG, Greil R, Filipcic L, Gnant M (2012) Tamoxifen and anastrozole as a sequencing strategy: a randomized controlled trial in patients with postmenopausal endocrine-responsive early breast cancer from the Austrian Breast and Colorectal Cancer Study Group. J Clin Oncol 30:722–728

    Article  CAS  PubMed  Google Scholar 

  7. Bliss JM, Kilburn LS, Coleman RE, Forbes JF, Coates AS, Jones SE, Jassem J, Delozier T, Andersen J, Paridaens R, van de Velde CJ, Lønning PE, Morden J, Reise J, Cisar L, Menschik T, Coombes RC (2012) Disease-related outcomes with long-term follow-up: an updated analysis of the intergroup exemestane study. J Clin Oncol 30:709–717

    Article  CAS  PubMed  Google Scholar 

  8. Ma CX, Adjei AA, Salavaggione OE, Coronel J, Pelleymounter L, Wang L, Eckloff BW, Schaid D, Wieben ED, Adjei AA, Weinshilboum RM (2005) Human aromatase: gene resequencing and functional genomics. Cancer Res 65:11071–11082

    Article  CAS  PubMed  Google Scholar 

  9. Aihara T, Takatsuka Y, Ohsumi S, Aogi K, Hozumi Y, Imoto S, Mukai H, Iwata H, Watanabe T, Shimizu C, Nakagami K, Tamura M, Ito T, Masuda N, Ogino N, Hisamatsu K, Mitsuyama S, Abe H, Tanaka S, Yamaguchi T, Ohashi Y (2010) 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. Breast Cancer Res Treat 121:379–387

    Article  CAS  PubMed  Google Scholar 

  10. Early Breast Cancer Trialists’ Collaborative Group (2005) Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomized trials. Lancet 365:1687–1717

    Article  Google Scholar 

  11. van Houwelingen HC (2007) Dynamic prediction by landmarking in event history analysis. Scand J Stat 34:70–85

    Article  Google Scholar 

  12. Coombes RC, Hall E, Gibson LJ, Paridaens R, Jassem J, Delozier T, Jones SE, Alvarez I, Bertelli G, Ortmann O, Coates AS, Bajetta E, Dodwell D, Coleman RE, Fallowfield LJ, Mickiewicz E, Andersen J, Lønning PE, Cocconi G, Stewart A, Stuart N, Snowdon CF, Carpentieri M, Massimini G, Bliss JM, van de Velde C; Intergroup Exemestane Study (2004) A randomized trial of exemestane after two to three years of tamoxifen therapy in postmenopausal women with primary breast cancer. N Engl J Med 350:1081–1092

    Article  Google Scholar 

  13. Coombes RC, Kilburn LS, Snowdon CF, Paridaens R, Coleman RE, Jones SE, Jassem J, Van de Velde CJ, Delozier T, Alvarez I, Del Mastro L, Ortmann O, Diedrich K, Coates AS, Bajetta E, Holmberg SB, Dodwell D, Mickiewicz E, Andersen J, Lønning PE, Cocconi G, Forbes J, Castiglione M, Stuart N, Stewart A, Fallowfield LJ, Bertelli G, Hall E, Bogle RG, Carpentieri M, Colajori E, Subar M, Ireland E, Bliss JM; Intergroup Exemestane Study (2007) Survival and safety of exemestane versus tamoxifen after 2–3 years’ tamoxifen treatment (Intergroup Exemestane Study): a randomised controlled trial. Lancet 369:559–570

    Article  Google Scholar 

  14. Goss PE, Ingle JN, Martino S, Robert NJ, Muss HB, Piccart MJ, Castiglione M, Tu D, Shepherd LE, Pritchard KI, Livingston RB, Davidson NE, Norton L, Perez EA, Abrams JS, Therasse P, Palmer MJ, Pater JL (2003) A randomized trial of letrozole in postmenopausal women after 5 years of tamoxifen therapy for early-stage breast cancer. N Engl J Med 349:1793–1802

    Article  CAS  PubMed  Google Scholar 

  15. Davies C, Pan H, Godwin J, Gray R, Arriagada R, Raina V, Abraham M, Medeiros Alencar VH, Badran A, Bonfill X, Bradbury J, Clarke M, Collins R, Davis SR, Delmestri A, Forbes JF, Haddad P, Hou MF, Inbar M, Khaled H, Kielanowska J, Kwan WH, Mathew BS, Mittra I, Müller B, Nicolucci A, Peralta O, Pernas F, Petruzelka L, Pienkowski T, Radhika R, Rajan B, Rubach MT, Tort S, Urrútia G, Valentini M, Wang Y, Peto R, Adjuvant Tamoxifen: Longer Against Shorter (ATLAS) Collaborative Group (2013) Long-term effects of continuing adjuvant tamoxifen to 10 years versus stopping at 5 years after diagnosis of oestrogen receptor-positive breast cancer: ATLAS, a randomised trial. Lancet 381:805–816

    Article  CAS  PubMed Central  PubMed  Google Scholar 

Download references

Acknowledgments

We thank Yumiko Nomura and her team for the excellent data management. We are indebted to all the patients and the investigators who participated in this trial, especially, to the investigators who have contributed to the data updating listed in the Appendix. This study was funded by the 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 provided financial contribution as a corporate sponsor took no part in this study other than providing information relevant to the proper use of study drugs. All decisions concerning the planning, implementation, and publication of this study were made by the executive committee of this study. This clinical trial complies with the current laws in Japan.

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Authors and Affiliations

  1. Breast Center, Aihara Hospital, 3-4-30, Makiochi, Minoh, Osaka, 562-0004, Japan

    Tomohiko Aihara

  2. Department of Biostatistics, The University of Tokyo, Tokyo, Japan

    Isao Yokota

  3. Department of Breast Oncology, Jichi Medical University, Shimotsuke, Tochigi, Japan

    Yasuo Hozumi

  4. Department of Breast Oncology, National Hospital Organization Shikoku Cancer Center, Matsuyama, Ehime, Japan

    Kenjiro Aogi

  5. Department of Breast Oncology, Aichi Cancer Center Hospital, Nagoya, Aichi, Japan

    Hiroji Iwata

  6. Department of Breast Surgery, Hokkaido Cancer Center, Hokkaido, Japan

    Motoshi Tamura

  7. Department of Surgery, Mitsui Memorial Hospital Tokyo, Tokyo, Japan

    Atsushi Fukuuchi

  8. Division of Breast Surgery, Niigata City General Hospital, Niigata, Japan

    Haruhiko Makino

  9. Department of Breast Surgery, Hiroshima Mark Clinic, Hiroshima, Japan

    Ryungsa Kim

  10. Department of Medical Oncology, Aichi Cancer Center Hospital, Nagoya, Aichi, Japan

    Masashi Andoh

  11. Division of Breast and Endocrine Surgery, Department of Surgery, St. Marianna University School of Medicine, Kawasaki, Kanagawa, Japan

    Koichiro Tsugawa

  12. Clinical Cancer Institute, National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan

    Shinji Ohno

  13. Department of Biostatistics, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan

    Takuhiro Yamaguchi

  14. Department of Integrated Science and Engineering for Sustainable Society, Chuo University, Tokyo, Japan

    Yasuo Ohashi

  15. Department of Medical Oncology, Hamamatsu Oncology Center, Shizuoka, Japan

    Toru Watanabe

  16. Department of Breast Surgery, Kansai Rosai Hospital, Amagasaki, Hyogo, Japan

    Yuichi Takatsuka

  17. Division of Oncology and Hematology, National Cancer Center Hospital East, Chiba, Japan

    Hirofumi Mukai

Authors
  1. Tomohiko Aihara
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  2. Isao Yokota
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  3. Yasuo Hozumi
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  4. Kenjiro Aogi
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  5. Hiroji Iwata
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  6. Motoshi Tamura
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  7. Atsushi Fukuuchi
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  8. Haruhiko Makino
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  9. Ryungsa Kim
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  10. Masashi Andoh
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  11. Koichiro Tsugawa
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  12. Shinji Ohno
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  13. Takuhiro Yamaguchi
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  14. Yasuo Ohashi
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  15. Toru Watanabe
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  16. Yuichi Takatsuka
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  17. Hirofumi Mukai
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Corresponding author

Correspondence to Tomohiko Aihara.

Appendix

Appendix

K. Aogi (NHO Shikoku Cancer Center), Y. Hozumi (Jichi Medical University Hospital), N. Wada (National Cancer Center Hospital East), C. Egawa (Kansai Rosai Hospital), H. Iwata (Aichi Cancer Center Hospital), Y. Fujiwara (National Cancer Center Hospital), K. Nakagami (Shizuoka General Hospital), M. Takahashi (NHO Hokkaido Cancer Center), T. Ito (Rinku General Medical Center), N. Ogino (Osaka Saiseikai Tondabayashi Hospital), M. Funakoshi (Hiroshima City Asa Hospital), S. Mitsuyama (Kitakyushu Municipal Medical Center), H. Abe (Shiga University of Medical Science), N. Masuda (NHO Osaka National Hospital), H. Tokura (Ashikaga Red Cross Hospital), S. Maeda (NHO Nagasaki Medical Center), S. Kamigaki (Sakai Municipal Hospital), S. Ohno (NHO National Kyushu Cancer Center), H. Yagata (St. Luke’s International Hospital), H. Arioka (Yokohama Rosai Hospital), S. Karamatsu (Toyokawa City Hospital), H. Kawaguchi (Matsuyama Red Cross Hospital), A. Fukuuchi (Mitsui Memorial Hospital), T. Sugimoto (Kochi Medical School Hospital), Y. Katayose (Akita City Hospital), N. Yamamoto (Chiba Cancer Center), S. Kuze (Chutoen General Medical Center), M. Okada (Hiroshima University Hospital), H. Matsumoto (Saitama Cancer Center), T. Saito (Saitma Red Cross Hospital), Y. Tokuda (Tokai University Hospital), H. Tomita (Niigata Prefectural Sakamachi Hospital), S. Hojo (Osaka Saiseikai Senri Hospital), R. Nishimura (Kumamoto Municipal Hospital), G. Amano (Nihonkai General Hospital), M. Yoshida (Seirei Hamamatsu General Hospital), Y. Park (Toho University Sakura Medical Center), T. Toyama (Nagoya City University Hospital), Y. Komoike (Kinki University Hospital, Faculty of Medicine), F. Tsukamoto (Osaka Koseinenkin Hospital), T. Kunihisa (Yodogawa Christian Hospital), M. Ochi (Miyoshi Central Hospital), A. Matsui (NHO Tokyo Medical Center), M. Inaba (Kanagawa Cancer Center), S. Nakano (Aichi Medical University Hospital), K. Hashimoto (Shimane Prefectural Central Hospital), H. Doihara (Okayama University Hospital), T. Watanabe (Sendai Medical Center), H. Tahara (The Institute of Medical Science, The University of Tokyo), Y. Tamaki (Osaka Medical Center for Cancer and Cardiovascular Diseases), S. Ozaki (Kochi Prefectural Hata Kenmin Hospital), M. Kitada (Asahikawa Medical University Hospital), K. Kuroi (Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital), M. Iguchi (Kanazawa University Hospital), F. Tanaka (Fukui Red Cross Hospital), N. Sonoda (Yurin Koseikai Fuji Hospital), A. Naito (Nagoya Kyouritsu Hospital), K. Kobayashi (Kinki Central Hospital), Y. Maehara (Kyushu University Hospital), M. Hashimoto (Iizuka Hospital), H. Kimura (Okayama Saiseikai General Hospital), S. Imoto (School of Medicine Kyorin University), T. Ri (Kyoto First Red Cross Hospital), S. Hara (Sasebo Municipal General Hospital), K. Okada (Uwajima City Hospital), J. Ando (Tochigi Cancer Center), K. Sakakibara (Nagoya City West Medical Center), M. Kuranami (Yamato Municipal Hospital)

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Aihara, T., Yokota, I., Hozumi, Y. et al. Anastrozole versus tamoxifen as adjuvant therapy for Japanese postmenopausal patients with hormone-responsive breast cancer: efficacy results of long-term follow-up data from the N-SAS BC 03 trial. Breast Cancer Res Treat 148, 337–343 (2014). https://doi.org/10.1007/s10549-014-3155-8

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