Skip to main content

Advertisement

SpringerLink
Log in

Durable complete response in HER2-positive breast cancer: a multicenter retrospective analysis

  • Clinical trial
  • Published:
Breast Cancer Research and Treatment Aims and scope Submit manuscript

Abstract

Purpose

Though advanced and metastatic epidermal growth factor receptor 2 (HER2)-positive disease is not curable, a small proportion of patients with HER2-positive metastatic breast cancer remain in prolonged complete remission with anti-HER2 treatment. We hypothesized that some cases of HER2-positive metastatic breast cancer may be curable. In this large, multicenter retrospective study, we aimed to assess the long-term outcomes for patients with a durable response to trastuzumab.

Methods

We retrospectively evaluated the data of patients diagnosed with HER2-positive metastatic breast cancer who received trastuzumab for more than 2 years as the first-line treatment. Patients diagnosed between April 1, 2001 and December 31, 2014 at 19 institutions in Japan were included in the analysis. From 124 potential subjects, 16 were excluded and 108 were evaluated.

Results

The median follow-up length was 7.7 years. Disease progression occurred in 44/108 (40.7%) patients and 13/108 (12%) patients died. The median progression-free survival was 11.2 years, and as more than 80% of patients were alive 10 years after metastatic breast cancer diagnosis. Of the 108 patients, 57 achieved a clinical complete response. Trastuzumab therapy was interrupted for 27 (47.4%) of these patients (based on the doctor’s recommendation for 19 patients, owing to adverse events for 4 patients, owing to unknown reasons for 3 patients, and at the request of 1 patient). Disease progression occurred in 4 of the 27 patients after the interruption of trastuzumab treatment. The median duration of trastuzumab therapy for all 27 patients was 5.1 years (0.9–9.3 years).

Conclusion

We found that some patients showed no evidence of disease after the interruption of trastuzumab therapy. Discontinuation of maintenance trastuzumab in this patient population after a limited time should be explored cautiously while awaiting a global collaborative effort for a randomized trial.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Iwamoto T, Fukui N, Kinoshita T et al (2015) Comprehensive prognostic report of the Japanese Breast Cancer Society registry in 2006. Breast Cancer 23(1):62–72

    Article  PubMed Central  Google Scholar 

  2. Cardoso F, Fallowfield L, Costa A et al (2011) Locally recurrent or metastatic breast cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 22(Suppl 6):vi25–vi30

    PubMed  Google Scholar 

  3. Giordano SH, Temin S, Kirshner JJ et al (2014) Systemic therapy for patients with advanced human epidermal growth factor receptor 2-positive breast cancer: American Society of Clinical Oncology clinical practice guideline. J Clin Oncol 32:2078–2099

    Article  CAS  PubMed  Google Scholar 

  4. Harano K, Lei X, Gonzalez-Angulo AM et al (2016) Clinicopathological and surgical factors associated with long-term survival in patients with HER2-positive metastatic breast cancer. Breast Cancer Res Treat 159:367–374

    Article  CAS  PubMed  Google Scholar 

  5. Yardley DA, Tripathy D, Brufsky AM et al (2014) Long-term survivor characteristics in HER2-positive metastatic breast cancer from registHER. Br J Cancer 110:2756–2764

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Swain SM, Baselga J, Kim SB et al (2015) Pertuzumab, trastuzumab, and docetaxel in HER2-positive metastatic breast cancer. N Engl J Med 372:724–734

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Witzel I, Muller V, Abenhardt W et al (2014) Long-term tumor remission under trastuzumab treatment for HER2 positive metastatic breast cancer—results from the HER-OS patient registry. BMC Cancer 14:806

    Article  PubMed  PubMed Central  Google Scholar 

  8. Beda M, Basso U, Ghiotto C, Monfardini S (2007) When should trastuzumab be stopped after achieving complete response in HER2-positive metastatic breast cancer patients? Tumori 93:491–492

    CAS  PubMed  Google Scholar 

  9. The World Health Organization (1983) Histological typing of breast tumors. Neoplasma 30:113–123

    Google Scholar 

  10. Tripathy D, Kaufman PA, Brufsky AM et al (2013) First-line treatment patterns and clinical outcomes in patients with HER2-positive and hormone receptor-positive metastatic breast cancer from registHER. Oncologist 18:501–510

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Clavarezza M, Puntoni M, Gennari A et al (2016) Dual block with lapatinib and trastuzumab versus single-agent trastuzumab combined with chemotherapy as neoadjuvant treatment of HER2-positive breast cancer: a meta-analysis of randomized trials. Clin Cancer Res 22:4594–4603

    Article  CAS  PubMed  Google Scholar 

  12. Gullo G, Zuradelli M, Sclafani F et al (2012) Durable complete response following chemotherapy and trastuzumab for metastatic HER2-positive breast cancer. Ann Oncol 23:2204–2205

    Article  CAS  PubMed  Google Scholar 

  13. Haq R, Gulasingam P (2016) Duration of trastuzumab in patients with HER2-positive metastatic breast cancer in prolonged remission. Curr Oncol 23:91–95

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Slamon DJ, Leyland-Jones B, Shak S et al (2001) Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med 344:783–792

    Article  CAS  PubMed  Google Scholar 

  15. von Minckwitz G, du Bois A, Schmidt M et al (2009) Trastuzumab beyond progression in human epidermal growth factor receptor 2-positive advanced breast cancer: a german breast group 26/breast international group 03-05 study. J Clin Oncol 27:1999–2006

    Article  Google Scholar 

  16. Tripathy D, Slamon DJ, Cobleigh M et al (2004) Safety of treatment of metastatic breast cancer with trastuzumab beyond disease progression. J Clin Oncol 22:1063–1070

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We would like to thank the following individuals for providing us with data on patients: Nobusuke Sasada; Hiroshima University Hospital, Mayumi Ishida; National Kyushu Cancer Center, Fukuoka, Japan, Keisei Anan; Kitakyushu Municipal Medical Center; Yasuyuki Kojima, St Marianna University School of Medicine, Hideaki Shigematsu; National Hospital Organization Kure Medical Center; and Hideaki Komatsu, Iwate Medical University School of Medicine. We would also like to thank Editage for providing editorial assistance.

Funding

This research is partially supported by the Practical Research for Innovative Cancer Control (15ck0106049h0002, 17ck0106307h0001) from the Japan Agency for Medical Research and Development, AMED, National Cancer Center Research and Development Fund (26-A-4).

Disclosure

Shigehira Saji received a research grant from Chugai Pharmaceutical Co. Ltd. Yutaka Tokuda received a research grant from Chugai Pharmaceutical Co., Ltd, Eisai Co. Ltd, and Novartis Pharma L.K. Hiroji Iwata holds honorarium in Chugai Pharmaceutical Co. Ltd. Norikazu Masuda holds honoraria in Chugai Pharmaceutical Co. Ltd and AstraZeneca. The other authors have declared no conflicts of interest.

Author information

Authors and Affiliations

  1. Departments of Breast and Endocrine Surgery, Tokai University School of Medicine, Kanagawa, 143 Shimokasuya, Isehara, Kanagawa, 259-1193, Japan

    Naoki Niikura, Rin Ogiya & Yutaka Tokuda

  2. Department of Breast and Medical Oncology, National Cancer Center, Tokyo, Japan

    Akihiko Shimomura & Kenji Tamura

  3. Department of Breast Surgical Oncology, St. Luke’s International Hospital, Tokyo, Japan

    Yumi Fukatsu

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

    Masataka Sawaki & Hhiroji Iwata

  5. Department of Surgery, Breast Oncology, National Hospital Organization Osaka National Hospital, Osaka, Japan

    Hiroyuki Yasojima & Norikazu Masuda

  6. Department of Breast Surgery, Gunma Prefectural Cancer Center, Gunma, Japan

    Tomomi Fujisawa

  7. Department of Breast Surgery, Hokkaido Cancer Center, Sapporo, Japan

    Mitsugu Yamamoto

  8. Department of Breast Surgery, Shizuoka General Hospital, Shizuoka, Japan

    Michiko Tsuneizumi

  9. Department of Breast Oncology, Sagara Hospital, Kagoshima, Japan

    Akira Kitani

  10. Division of Breast Oncology, Shizuoka Cancer Center, Shizuoka, Japan

    Junichiro Watanabe

  11. Department of Surgery, National Hospital Organization, Tokyo Medical Center, Tokyo, Japan

    Akira Matsui

  12. Departments of Breast and Endocrine Surgery, Okayama University Hospital, Okayama, Japan

    Yuko Takahashi & Tadatoshi Shien

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

    Seiki Takashima

  14. Department of Medical Oncology, Fukushima Medical University, Fukushima, Japan

    Shigehira Saji

Authors
  1. Naoki Niikura
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Akihiko Shimomura
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yumi Fukatsu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Masataka Sawaki
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Rin Ogiya
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Hiroyuki Yasojima
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Tomomi Fujisawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Mitsugu Yamamoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Michiko Tsuneizumi
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Akira Kitani
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Junichiro Watanabe
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Akira Matsui
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Yuko Takahashi
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Seiki Takashima
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Tadatoshi Shien
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Kenji Tamura
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. Shigehira Saji
    View author publications

    You can also search for this author in PubMed Google Scholar

  18. Norikazu Masuda
    View author publications

    You can also search for this author in PubMed Google Scholar

  19. Yutaka Tokuda
    View author publications

    You can also search for this author in PubMed Google Scholar

  20. Hhiroji Iwata
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Naoki Niikura.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Niikura, N., Shimomura, A., Fukatsu, Y. et al. Durable complete response in HER2-positive breast cancer: a multicenter retrospective analysis. Breast Cancer Res Treat 167, 81–87 (2018). https://doi.org/10.1007/s10549-017-4489-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10549-017-4489-9

Keywords

Search

Navigation