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Outcomes of trastuzumab therapy in HER2-positive early breast cancer patients

  • Original Article
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International Journal of Clinical Oncology Aims and scope Submit manuscript

An Erratum to this article was published on 14 March 2015

Abstract

Background

Previous large trials with trastuzumab (TZM) showed improved outcome in patients with HER2-positive early-stage breast cancer. However, the efficacy and safety of TZM in Japanese patients have not been fully evaluated. We have therefore conducted an observational study in Japan.

Methods

This was a retrospective and a prospective observational study in which data on women with histologically confirmed HER2-positive invasive breast cancer who received TZM for stage I–IIIC disease were collected from 56 institutions that participated in the Japan Breast Cancer Research Group and the efficacy of each treatment regimen analyzed.

Results

A total of 2,024 patients treated between July 2009 and June 2011 were initially enrolled in this study; in August 2013, the patient cohort comprised 2,009 patients. Of these, 142 (7.5 %) were aged ≥70 years, 1,097 (58.1 %) had clinically node-negative (cN0) breast cancer, and 883 (47.4 %) were estrogen receptor-positive. Treatment options were neoadjuvant therapy (662 patients) and adjuvant therapy with TZM (1,228 patients). Three-year overall survival (OS) rates in the entire cohort and in the neoadjuvant and adjuvant cohorts, respectively, were 98.9 [95 % confidence interval (CI) 98.2–99.3], 98.3 (95 % CI 96.8–99.1 %), and 99.2 % (95 % CI 98.4–99.6), respectively. Three-year disease-free survival (DFS) rates in the entire cohort and in the neoadjuvant and adjuvant cohorts, respectively were 94.2 (95 % CI 93.0–95.2), 94.8 (95 % CI 93.0–95.9), and 93.1 (95 % CI 90.7–94.9 %), respectively. Multivariate analysis showed that age and nodal status negatively correlated with DFS. Age was the only factor which correlated with OS rate. Adverse events (AEs) associated with TZM and grade 3/4 AEs were reported in 356 (18.8 %) and 14 (0.6 %) patients, respectively. Grade 3/4 cardiac toxicities were reported in 11 patients.

Conclusion

Based on data from our patient cohort of Japanese women with HER2-positive early-stage breast cancer, the efficacy and safety of systemic therapy with TZM are comparable to data from previously conducted large trials. Progress in anti-HER2 therapy for patients aged ≥70 years who have a poorer prognosis is needed.

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Acknowledgments

The authors are grateful to all of the co-investigators and patients for their cooperation in the JBCRG C-01 study. They also thank the following additional investigators for their contributions to this study: K. Yamagami (Shinko Hospital), T. Morimoto (Yao Municipal Hospital), Y. Hasegawa (Hirosaki Municipal Hospital), H. Shigematsu (Hiroshima University Hospital), M. Hosoda (Hokkaido University Hospital), H. Abe (Bell Land General Hospital), D. Yotsumoto (Social Medical Corporation Hakuaikai Sagara Hospital), H. Tanino (Kitasato University Hospital), Y. Yamamoto (Kumamoto University Hospital), K. Hisamatsu (Oikawa Hospital), T. Aihara (Aihara Hospital), H. Bando (University of Tsukuba Hospital), H. Yoshibayashi (Japanese Red Cross Wakayama Medical Center), N. Tagaya (Dokkyo Medical University), H. Doihara (Okayama University Hospital), K. Narui (Yokohama City University Medical Center), H. Mukai (National Cancer Center Higashi Hospital), K. Aogi (National Hospital Organization Shikoku Cancer Center), S. Tsuyuki (Osaka Red Cross Hospital), Y. Kawabuchi (Hiroshima General Hospital), Y. Wada (National Hospital Organization Himeji Medical Center), Y. Kakugawa (Miyagi Cancer Center), Y. Moriguchi (Kyoto City Hospital), Y. Kawaguchi (Murakami Memorial Hospital Asahi University), H. Suwa (Hyogo Prefectural Tsukaguchi Hospital), F. Tanaka (Fukui Red Cross Hospital), H. Nakagomi (Yamanashi Prefectural Central Hospital), T. Ito (Rinku General Medical Center), S. Nakamura (Showa University Hospital), H. Takeuchi (Beppu Medical Center), M. Inokuchi (Kanazawa University Hospital), Y. Teramura (Hikone Municipal Hospital), K. Ito (Shinshu University School of Medicine), S. Sato (Ichinomiya Municipal Hospital), F. Yotsumoto (Shiga Medical Center for Adults), T. Okino (Kohka Public Hospital), Y. Mitsudo (Mitsubishi Kyoto Hospital), K. Yoshidome (Osaka Police Hospital), and Y. Tokunaga (Osakakita Teishin Hospital). The authors also thank Tetsuo Takeuchi for statistical work, Sachiko Inoue and Miyoko Hasebe for data management, and Kiyomi Kashiwa and Nobuko Aoki for secretarial work.

Conflict of interest

This study was conducted using our own funds from JBCRG. The Department of EBM Research, Institute for Advancement of Clinical and Translational Science was partially funded from Chugai Pharmaceutical Co., Ltd. H. Yamshiro and S. Ohno received an honorarium from Chugai, Novartis, and AstraZeneca. H. Iwata and R. Nishimura, N. Sato, T. Takano, S. Morita and M. Toi received an honorarium from from Chugai. N. Masuda received an honorarium from Chugai, Eisai and AstraZeneca. M. Takada received an honorarium from Eisai. H. Iwata, T. Takano, S. Yasuno, S. Morita and M. Toi received research funding from Chugai. N. Yamamoto received research funding from Pfizer Japan and Bayer. S. Yasuno received research funding from Pfizer Japan. H. Iwata recieved research funding from GSK. All other authors declare no conflicts of interest.

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Authors and Affiliations

  1. Department of Breast Surgery, Tenri Hospital, 200 Mishima-cho, Tenri, Nara, 632-8552, Japan

    Hiroyasu Yamshiro

  2. Department of Breast Oncology, Aichi Cancer Center Hospital, 1-1 Kanokoden, Chikusa-ku, Nagoya, Aichi, 464-8681, Japan

    Hiroji Iwata

  3. Surgery, Breast Oncology, NHO Osaka National Hospital, 2-1-14 Hohenzaka, Chuo-ku, Osaka, 540-0006, Japan

    Norikazu Masuda

  4. Division of Breast Surgery, Chiba Cancer Center, 666-2 Nitona-cho, Chuo-ku, Chiba, 260-8717, Japan

    Naohito Yamamoto

  5. Department of Breast and Endocrine Surgery, Kumamoto City Hospital, 1-1-60 Kotoh, Higashi-ku, Kumamoto City, Kumamoto, 862-8505, Japan

    Reiki Nishimura

  6. Breast Surgery, Hiroshima City Hospital, 7-33 Motomachi, Naka-ku, Hiroshima-sh, Hiroshima, 730-8518, Japan

    Shoichiro Ohtani

  7. Department of Breast Oncology, Niigata Cancer Center Hospital, 2-15-3 Kawagishi Town, Chuo-ku, Niigata, 951-8566, Japan

    Nobuki Sato

  8. Department of Breast Surgery, NHO Hokkaido Cancer Center, 4-2 Kikusui, Shiroishi-ku, Sapporo, Hokkaido, 090-0011, Japan

    Masato Takahashi

  9. Department of Surgery II, Tokyo Women’s Medical University, 8-1 Kawadacho, Shinjuku-ku, Tokyo, 162-8666, Japan

    Takako Kamio

  10. Japanese Red Cross Hokkaido, College of Nursing, 664-1 Akebono-cho, Kitami, Hokkaido, 090-0011, Japan

    Kosuke Yamazaki

  11. Department of Breast Surgery, Saitama Red Cross Hospital, 8-3-33 Kamiochiai, Chuo-ku, Saitama-shi, Saitama, 338-8553, Japan

    Tsuyoshi Saito

  12. Kato Breast Surgery Clinic, 8-12 Nishiojicho, Kusatsu, Shiga, 525-0037, Japan

    Makoto Kato

  13. Department of Breast Surgery, Japanese Red Cross Kyoto Daiichi Hospital, 15-749 Honmachi, Higashiyama-ku, Kyoto, 605-0981, Japan

    Tecchuu Lee

  14. Clinical Research Institute, NHO Kyusyu Cancer Center, 3-1-1 Notame, Minami-ku, Fukuoka, 811-1395, Japan

    Shinji Ohno

  15. Department of Breast Surgery, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, 3-18-22 Honkomagome, Bunkyo-ku, Tokyo, 113-8677, Japan

    Katsumasa Kuroi

  16. Department of Medical Oncology, Toranomon Hospital, 2-2-2 Toranomon, Minato-ku, Tokyo, 105-8470, Japan

    Toshimi Takano

  17. Department of Surgery (Breast Surgery), Kyoto University Hospital, 54 Kawaharacho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan

    Masahiro Takada

  18. Department of EBM Research, Institute for Advancement of Clinical and Translational Science, Kyoto University Hospital, 54 Kawaharacho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan

    Shinji Yasuno

  19. Department of Biomedical Statistics and Bioinformatics, Kyoto University Graduate School of Medicine, 54 Kawaharacho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan

    Satoshi Morita

  20. Department of Surgery (Breast Surgery), Graduate School of Medicine, Kyoto University, 54 Kawaharacho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan

    Masakazu Toi

Authors
  1. Hiroyasu Yamshiro
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  2. Hiroji Iwata
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  3. Norikazu Masuda
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  4. Naohito Yamamoto
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  5. Reiki Nishimura
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  6. Shoichiro Ohtani
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  7. Nobuki Sato
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  8. Masato Takahashi
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  9. Takako Kamio
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  10. Kosuke Yamazaki
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  11. Tsuyoshi Saito
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  12. Makoto Kato
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  13. Tecchuu Lee
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  14. Shinji Ohno
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  15. Katsumasa Kuroi
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  16. Toshimi Takano
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  17. Masahiro Takada
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  18. Shinji Yasuno
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  19. Satoshi Morita
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  20. Masakazu Toi
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Corresponding author

Correspondence to Hiroyasu Yamshiro.

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Yamshiro, H., Iwata, H., Masuda, N. et al. Outcomes of trastuzumab therapy in HER2-positive early breast cancer patients. Int J Clin Oncol 20, 709–722 (2015). https://doi.org/10.1007/s10147-015-0785-8

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  • DOI: https://doi.org/10.1007/s10147-015-0785-8

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