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Survival of HER2-positive primary breast cancer patients treated by neoadjuvant chemotherapy plus trastuzumab: a multicenter retrospective observational study (JBCRG-C03 study)

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Abstract

We investigated the disease-free survival (DFS) of HER2-positive primary breast cancer patients treated with neoadjuvant chemotherapy plus trastuzumab, as well as predictive factors for DFS and pathologic response. Data from 829 female patients treated between 2001 and 2010 were collected from 38 institutions in Japan. Predictive factors were evaluated using multivariate analyses. The 3-year DFS rate was 87 % [95 % confidence interval (CI) 85–90]. The pathologic complete response (pCR: ypT0/is + ypN0) rate was 51 %. The pCR rate was higher in the ER/PgR-negative patients than in the ER/PgR-positive patients (64 vs. 36 %, P < 0.001). Patients with pCR showed a higher DFS rate than patients without pCR (93 vs. 82 %, P < 0.001). Multivariate analysis revealed three independent predictors for poorer DFS: advanced nodal stage [hazard ratio (HR) 2.63, 95 % CI 1.36–5.21, P = 0.004 for cN2–3 vs. cN0], histological/nuclear grade 3 (HR 1.81, 95 % CI 1.15–2.91, P = 0.011), and non-pCR (HR 1.98, 95 % CI 1.22–3.24, P = 0.005). In the ER/PgR-negative dataset, non-pCR (HR 2.63, 95 % CI 1.43–4.90, P = 0.002) and clinical tumor stage (HR 2.20, 95 % CI 1.16–4.20, P = 0.017 for cT3–4 vs. cT1–2) were independent predictors for DFS, and in the ER/PgR-positive dataset, histological grade of 3 (HR 3.09, 95 % CI 1.48–6.62, P = 0.003), clinical nodal stage (HR 4.26, 95 % CI 1.53–13.14, P = 0.005 for cN2–3 vs. cN0), and young age (HR 2.40, 95 % CI 1.12–4.94, P = 0.026 for ≤40 vs. >40) were negative predictors for DFS. Strict pCR (ypT0 + ypN0) was an independent predictor for DFS in both the ER/PgR-negative and -positive datasets (HR 2.66, 95 % CI 1.31–5.97, P = 0.006 and HR 3.86, 95 % CI 1.13–24.21, P = 0.029, respectively). These results may help assure a more accurate prognosis and personalized treatment for HER2-positive breast cancer patients.

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Acknowledgments

We thank the patients who participated in this study. We also thank our colleagues who participated in this study and are not included in the list of authors, in alphabetical order: Y. Hasegawa (Hirosaki Municipal Hospital), K. Hisamatsu (Oikawa Hospital), Y. Horimoto (Juntendo University School of Medicine), Y. Kakugawa (Miyagi Cancer Center), A. Kitani (Tokyo Kyosai Hospital), Y. Kokawa (Wakayama Medical University), G. Kutomi (Sapporo Medical University School of Medicine), Y. Moriguchi (Kyoto City Hospital), T. Morimoto (Yao Municipal Hospital), H. Nakagomi (Yamanashi Prefectural Central Hospital), K. Narui (Yokohama City University Medical Center), M. Ohara (Hiroshima Prefectural Hospital), T. Saito (Saitama Red Cross Hospital), T. Sato (Niigata Prefectural Central Hospital), H. Shigematsu (Research Institute for Radiation Biology and Medicine, Hiroshima University), K. Shingu (Iida Municipal Hospital), H. Sugiura (Nagoya City West Medical Center), M. Takahashi (Hokkaido Cancer Center), H. Takeuchi (National Hospital Organization Beppu Medical Center), K. Yamagami (Shinko Hospital), K. Yamazaki (Sapporo-Kotoni Breast Clinic), and K. Yoshida (Gifu University Hospital). We appreciate the contributions to data management of Tetsuhiro Sakai and Aya Maruyama from the JBCRG data canter. This work was supported by research grants from the Ministry of Health, Labour and Welfare of Japan (Nos. H18-3JIGAN-IPPAN-007 and H22-GANRINSHO-IPPAN-039).

Conflict of interest

H. Iwata, S. Ohno, N. Masuda, and S. Morita received honorarium from Chugai Pharmaceutical Co., Ltd. N. Masuda received honorarium from Eisai Co., Ltd. M. Toi is currently conducting research sponsored by Chugai Pharmaceutical Co., Ltd. and received donation from Chugai Pharmaceutical Co., Ltd. All remaining authors have declared no conflicts of interest.

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Authors and Affiliations

  1. Department of Breast Surgery, Graduate School of Medicine, Kyoto University, 54 Kawaracho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan

    M. Takada & M. Toi

  2. Outpatient Oncology Unit, Kyoto University Hospital, Kyoto, Japan

    H. Ishiguro

  3. Department of Breast Oncology, Saitama Cancer Center, Saitama, Japan

    S. Nagai

  4. Department of Breast Surgery, Hiroshima City Hospital, Hiroshima, Japan

    S. Ohtani

  5. Department of Breast and Endocrine Surgery, Toranomon Hospital, Tokyo, Japan

    H. Kawabata

  6. Department of Breast Oncology, Gunma Prefectural Cancer Center, Ota, Japan

    Y. Yanagita

  7. Department of Breast Oncology, Jichi Medical University Hospital, Shimotsuke, Japan

    Y. Hozumi

  8. Breast and Medical Oncology Division, National Cancer Center Hospital, Tokyo, Japan

    C. Shimizu

  9. Department of Breast Surgery, Hyogo Cancer Center, Akashi, Japan

    S. Takao

  10. Department of Breast Oncology, Niigata Cancer Center Hospital, Niigata, Japan

    N. Sato

  11. Department of Surgery, Kitasato University School of Medicine, Sagamihara, Japan

    Y. Kosaka

  12. Breast Surgical Oncology, Social Medical Corporation Hakuaikai, Sagara Hospital, Kagoshima, Japan

    Y. Sagara

  13. Department of Breast Oncology, Aichi Cancer Center, Nagoya, Japan

    H. Iwata

  14. Clinical Cancer Center, National Kyushu Cancer Center, Fukuoka, Japan

    S. Ohno

  15. Department of Surgery, Tokyo Metropolitan Cancer and Infectious Diseases Centre, Komagome Hospital, Tokyo, Japan

    K. Kuroi

  16. Department of Surgery, Breast Oncology, Osaka National Hospital, Osaka, Japan

    N. Masuda

  17. Department of Breast Surgery, National Hospital Organization Kure Medical Center, Kure, Japan

    H. Yamashiro

  18. Institute for Advanced Biosciences, Keio University, Tsuruoka, Japan

    M. Sugimoto & Y. Naito

  19. Department of Health Care Policy and Health Economics, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan

    M. Kondo

  20. Department of Environment and Information Studies, Keio University, Fujisawa, Japan

    Y. Naito

  21. Systems Biology Program, Graduate School of Media and Governance, Keio University, Fujisawa, Japan

    Y. Naito

  22. Department of Pathology, Tohoku University Hospital and School of Medicine, Sendai, Japan

    H. Sasano

  23. Faculty of Health Care, Tenri Health Care University, Tenri, Japan

    T. Inamoto

  24. Department of Biomedical Statistics and Bioinformatics, Kyoto University Graduate School of Medicine, Kyoto, Japan

    S. Morita

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  1. M. Takada
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  2. H. Ishiguro
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  3. S. Nagai
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  4. S. Ohtani
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  5. H. Kawabata
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  6. Y. Yanagita
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  7. Y. Hozumi
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  8. C. Shimizu
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  9. S. Takao
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  10. N. Sato
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  11. Y. Kosaka
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  12. Y. Sagara
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  13. H. Iwata
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  14. S. Ohno
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  15. K. Kuroi
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  16. N. Masuda
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  17. H. Yamashiro
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  18. M. Sugimoto
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  19. M. Kondo
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  20. Y. Naito
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  21. H. Sasano
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  22. T. Inamoto
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  23. S. Morita
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  24. M. Toi
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Correspondence to M. Toi.

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On behalf of the JBCRG-C03 Collaborative Group.

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Takada, M., Ishiguro, H., Nagai, S. et al. Survival of HER2-positive primary breast cancer patients treated by neoadjuvant chemotherapy plus trastuzumab: a multicenter retrospective observational study (JBCRG-C03 study). Breast Cancer Res Treat 145, 143–153 (2014). https://doi.org/10.1007/s10549-014-2907-9

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