Skip to main content

Advertisement

SpringerLink
Log in

Dose-dense adjuvant chemotherapy: a systematic review and meta-analysis of the Japanese Breast Cancer Society Clinical Practice Guideline, 2018 edition

  • Special Feature
  • Meta-analyses from the Japanese Breast Cancer Society: clinical practice guidelines for breast cancer
  • Published:
Breast Cancer Aims and scope Submit manuscript

Abstract

Increasing the dose intensity of cytotoxic therapy by shortening the intervals between cycles may enhance efficacy. Dose-dense chemotherapy, which is adopted as adjuvant chemotherapy of high-risk breast cancer, is addressed in the Japanese Breast Cancer Society Clinical Practice Guideline for breast cancer, 2018 edition (in Japanese). To evaluate the benefits and safety of dose-dense adjuvant chemotherapy described in the guideline, we performed a systematic review and meta-analysis of data of randomized trials using the same drugs, doses, and numbers of cycles. The PubMed, Cochrane Library, and Ichushi-Web databases were searched for relevant publications reporting randomized trials published until November 2016. Overall survival (OS), disease-free survival (DFS), and toxicity were assessed. Three trials comprising 5190 patients were included. Compared with conventional chemotherapy, dose-dense chemotherapy lengthened OS (RR = 0.76; 95% CI = 0.64–0.90) and DFS (RR = 0.83; 95% CI = 0.75–0.92) and increased the risk of anemia (RR = 4.56; 95% CI = 2.01–10.34). We conclude that dose-dense chemotherapy can be highly recommended as adjuvant chemotherapy for patients with breast cancer with a high risk of recurrence risk and sufficient bone marrow function.

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
Fig. 4

Similar content being viewed by others

References

  1. Early Breast Cancer Trialists’ Collaborative Group (EBCTCG), Peto R, Davies C, Godwin J, Gray R, et al. Comparisons between different polychemotherapy regimens for early breast cancer: meta-analyses of long-term outcome among 100,000 women in 123 randomised trials. Lancet. 2012;379:432–44.

    Article  Google Scholar 

  2. Norton L, Simon R. Tumor size, sensitivity to therapy, and design of treatment schedules. Cancer Treat Rep. 1977;61:1307–17.

    CAS  PubMed  Google Scholar 

  3. Norton LA. A Gompertzian model of human breast cancer growth. Cancer Res. 1988;48(24, pt 1):7067.

    CAS  PubMed  Google Scholar 

  4. Del Mastro L, De Placido S, Bruzzi P, De Laurentiis M, Boni C, et al. Fluorouracil and dose-dense chemotherapy in adjuvant treatment of patients with early-stage breast cancer: an open-label, 2  ×  2 factorial, randomised phase 3 trial. Lancet. 2015;385:1863–72.

    Article  Google Scholar 

  5. Venturini M, Del Mastro L, Aitini E, Baldini E, Caroti C, et al. Dose-dense adjuvant chemotherapy in early breast cancer patients: results from a randomized trial. J Natl Cancer Inst. 2005;97:1724–33.

    Article  CAS  Google Scholar 

  6. Citron ML, Berry DA, Cirrincione C, Hudis C, Winer EP, et al. Randomized trial of dose-dense versus conventionally scheduled and sequential versus concurrent combination chemotherapy as postoperative adjuvant treatment of node-positive primary breast cancer: first report of Intergroup Trial C9741/Cancer and Leukemia Group B Trial 9741. J Clin Oncol. 2003;21:1431–9.

    Article  CAS  Google Scholar 

  7. Foukakis T, von Minckwitz G, Bengtsson NO, Brandberg Y, Wallberg B, et al. Effect of tailored dose-dense chemotherapy vs standard 3-weekly adjuvant chemotherapy on recurrence-free survival among women with high-risk early breast cancer: a randomized clinical trial. JAMA. 2016;316:1888–96.

    Article  CAS  Google Scholar 

  8. Burnell M, Levine MN, Chapman JA, Bramwell V, Gelmon K, et al. Cyclophosphamide, epirubicin, and fluorouracil versus dose-dense epirubicin and cyclophosphamide followed by paclitaxel versus doxorubicin and cyclophosphamide followed by paclitaxel in node-positive or high-risk node-negative breast cancer. J Clin Oncol. 2010;28:77–82.

    Article  CAS  Google Scholar 

  9. Therasse P, Mauriac L, Welnicka-Jaskiewicz M, Bruning P, Cufer T, et al. Final results of a randomized phase III trial comparing cyclophosphamide, epirubicin, and fluorouracil with a dose-intensified epirubicin and cyclophosphamide + filgrastim as neoadjuvant treatment in locally advanced breast cancer: an EORTC-NCIC-SAKK multicenter study. J Clin Oncol. 2003;21:843–50.

    Article  CAS  Google Scholar 

  10. von Minckwitz G, Raab G, Caputo A, Schütte M, Hilfrich J, et al. Doxorubicin with cyclophosphamide followed by docetaxel every 21 days compared with doxorubicin and docetaxel every 14 days as preoperative treatment in operable breast cancer: the GEPARDUO study of the German Breast Group. J Clin Oncol. 2005;23:2676–85.

    Article  Google Scholar 

  11. Kojimahara N, Nakayama T, Morizane T, Yamaguchi N, Yoshida M. Minds manual for guideline development. Ver. 2.0. Tokyo: Japan Council for Quality Health Care; 2016.

    Google Scholar 

  12. Shea BJ, Hamel C, Wells GA, Bouter LM, Kristjansson E, et al. AMSTAR is a reliable and valid measurement tool to assess the methodological quality of systematic reviews. J Clin Epidemiol. 2009;62:1013–20.

    Article  Google Scholar 

  13. Bonilla L, Ben-Aharon I, Vidal L, Gafter-Gvili A, Leibovici L, et al. Dose-dense chemotherapy in nonmetastatic breast cancer: a systematic review and meta-analysis of randomized controlled trials. J Natl Cancer Inst. 2010;102:1845–54.

    Article  CAS  Google Scholar 

Download references

Funding

This meta-analysis was performed as one of the activities by Japanese Breast Cancer Society.

Author information

Authors and Affiliations

  1. Department of Breast and Endocrine Surgery, Osaka University Graduate School of Medicine, 2-2-E10 Yamadaoka, Suita, Osaka, 565-0871, Japan

    Tetsuhiro Yoshinami

  2. First Department of Surgery, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu, Shizuoka, 431-3192, Japan

    Kei Koizumi

  3. Department of Breast Oncology, Saitama Cancer Center, 780 Komuro, Ina-machi, Kitaadachi-gun, Saitama, 362-0806, Japan

    Shigenori E. Nagai

  4. Department of Breast Surgery, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, 467-8601, Japan

    Tatsuya Toyama

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

    Hiroji Iwata

Authors
  1. Tetsuhiro Yoshinami
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kei Koizumi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Shigenori E. Nagai
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Tatsuya Toyama
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Hiroji Iwata
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Tetsuhiro Yoshinami.

Ethics declarations

Conflict of interest

Tetsuhiro Yoshinami received honoraria from Chugai, Kyowa Kirin, Novartis and Pfizer. Kei Koizumi received honoraria from Pfizer, Chugai, Eisai, Eli Lilly, Novartis, AstraZeneca, Merck Serono, Genomic Health, Allergan Japan, Kyowa Kirin, Daiichi Sankyo and Taiho. Shigenori E. Nagai received research funding from Chugai and Nippon Kayaku, and honoraria from Chugai, Novartis, Pfizer, Eli Lilly, Eisai and Taiho. Tatsuya Toyama received research funding from Chugai, Novartis, Eisai and AstraZeneca and honoraria from Chugai, Novartis, Eisai, AstraZeneca, Lilly, Kyowa Hakko Kirin, Taiho, Daiichi Sankyo, Nippon Kayaku, Pizer and Takeda. Hiroji Iwata received research funding from Chugai, Novartis, MSD and Lilly, honoraria from Chugai, AstraZeneca and Daiichi Sankyo, and serves as an advisory board to Daiichi Sankyo, Chugai, Lilly, Kyowa Hakko Kirin, Pfizer, Novartis and AstraZeneca.

Ethical approval

For this type of study, formal consent is not required.

Informed consent

For this type of study, formal consent is not required.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Tetsuhiro Yoshinami, Kei Koizumi, Shigenori E. Nagai, Tatsuya Toyama, Hiroji Iwata: the Japanese Breast Cancer Society Clinical Practice Guideline for systemic treatment of breast cancer panel membership.

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Yoshinami, T., Koizumi, K., Nagai, S.E. et al. Dose-dense adjuvant chemotherapy: a systematic review and meta-analysis of the Japanese Breast Cancer Society Clinical Practice Guideline, 2018 edition. Breast Cancer 27, 334–339 (2020). https://doi.org/10.1007/s12282-019-01039-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12282-019-01039-1

Keywords

Search

Navigation