Skip to main content
Top
Published in: Breast Cancer 1/2017

01-01-2017 | Original Article

Docetaxel and cyclophosphamide as neoadjuvant chemotherapy in HER2-negative primary breast cancer

Authors: Katsuhiko Nakatsukasa, Hiroshi Koyama, Yoshimi Oouchi, Seiichi Imanishi, Naruhiko Mizuta, Kouichi Sakaguchi, Yoshifumi Fujita, Ikuya Fujiwara, Tatsuya Kotani, Takayuki Matsuda, Kenichirou Fukuda, Midori Morita, Sadao Kawakami, Yayoi Kadotani, Eiichi Konishi, Akio Yanagisawa, Tetsuya Taguchi

Published in: Breast Cancer | Issue 1/2017

Login to get access

Abstract

Background

Docetaxel plus cyclophosphamide (TC) has recently been established as a standard adjuvant chemotherapy regimen for HER2-negative (HER2−) operable breast cancer. However, the efficacy and tolerability of TC as neoadjuvant chemotherapy (NAC) remain unclear. We, therefore, conducted a prospective study to evaluate the efficacy of TC NAC in HER2− primary breast cancer.

Methods

Patients who were diagnosed with HER2−, N0–N1, invasive breast cancer between July 2011 and February 2014 and had tumors measuring 1–7 cm were eligible. The subtypes were classified using a core-needle or vacuum-assisted breast biopsy. The efficacy and safety of NAC comprising TC (75 mg/m2 docetaxel and 600 mg/m2 cyclophosphamide, four cycles every 3 weeks) were investigated in a prospective study in patients with HER2− breast cancer.

Results

Fifty-two patients were enrolled. Of these, 94.2 % (49/52) completed four cycles of TC. The overall pCR rate was 16.3 % (8/49). The pCR rates for patients with luminal A-like breast cancer [estrogen receptor-positive (ER+), Ki67 index of <20 %, and HER2−], luminal B-like breast cancer (ER+, Ki67 index of >20 %, and HER2−), and triple-negative breast cancer [ER-negative (ER−) and HER2−] were 0 % (0/12), 4.3 % (1/23), and 50.0 % (7/14), respectively. Almost all pCRs occurred in triple-negative breast cancer patients.

Conclusions

The pCR rate of TC NAC was not very high despite the high completion rate. TC NAC was effective against the triple-negative subtype, resulting in a higher pCR rate. Therefore, our results indicated that TC NAC showed limited efficacy in luminal subtype breast cancer with the exception of the triple-negative subtype.
Literature
1.
go back to reference Wolmark N, Wnag J, Mamounas E, Bryant J, Fisher B. Prospective chemotherapy in patients with operable breast cancer: nine-year results from National Surgical Adjuvant Breast and Bowel Project B-18. J Natl Cancer Inst Monogr. 2001;30:96–102.CrossRef Wolmark N, Wnag J, Mamounas E, Bryant J, Fisher B. Prospective chemotherapy in patients with operable breast cancer: nine-year results from National Surgical Adjuvant Breast and Bowel Project B-18. J Natl Cancer Inst Monogr. 2001;30:96–102.CrossRef
2.
go back to reference Bear HD, Anderson S, Brown A, Smith R, Mamounas EP, Fisher B, et al. The effect on tumor response of adding sequential preoperative docetaxel to preoperative doxorubicin and cyclophosphamide: preliminary results from National Surgical Adjuvant Breast and Bowel Project Protocol B-27. J Clin Oncol. 2003;21:4165–74.CrossRefPubMed Bear HD, Anderson S, Brown A, Smith R, Mamounas EP, Fisher B, et al. The effect on tumor response of adding sequential preoperative docetaxel to preoperative doxorubicin and cyclophosphamide: preliminary results from National Surgical Adjuvant Breast and Bowel Project Protocol B-27. J Clin Oncol. 2003;21:4165–74.CrossRefPubMed
3.
go back to reference Heys SD, Hutcheon AW, Sarkar TK, Ogston KN, Miller ID, Payne S, et al. Neoadjuvant docetaxel in breast cancer: 3-year survival results from the Aberdeen trial. Clin Breast Cancer. 2002;3(Suppl 2):S69–74.CrossRefPubMed Heys SD, Hutcheon AW, Sarkar TK, Ogston KN, Miller ID, Payne S, et al. Neoadjuvant docetaxel in breast cancer: 3-year survival results from the Aberdeen trial. Clin Breast Cancer. 2002;3(Suppl 2):S69–74.CrossRefPubMed
4.
go back to reference Henderson IC, Berry DA, Demetri GD, Cirrincione CT, Goldstein LJ, Martino S, et al. Improved outcomes from adding sequential paclitaxel but not from escalating doxorubicin dose in an adjuvant chemotherapy regimen for patients with node-positive primary breast cancer. J Clin Oncol. 2003;21:976–83.CrossRefPubMed Henderson IC, Berry DA, Demetri GD, Cirrincione CT, Goldstein LJ, Martino S, et al. Improved outcomes from adding sequential paclitaxel but not from escalating doxorubicin dose in an adjuvant chemotherapy regimen for patients with node-positive primary breast cancer. J Clin Oncol. 2003;21:976–83.CrossRefPubMed
5.
go back to reference Jones S, Holmes FA, O’Shaughnessy J, Blum JL, Vukelja SJ, McIntyre KJ, et al. Docetaxel with cyclophosphamide is associated with an overall survival benefit compared with doxorubicin and cyclophosphamide: 7-year follow-up of US Oncology Research Trial 9735. J Clin Oncol. 2009;27:1177–83.CrossRefPubMed Jones S, Holmes FA, O’Shaughnessy J, Blum JL, Vukelja SJ, McIntyre KJ, et al. Docetaxel with cyclophosphamide is associated with an overall survival benefit compared with doxorubicin and cyclophosphamide: 7-year follow-up of US Oncology Research Trial 9735. J Clin Oncol. 2009;27:1177–83.CrossRefPubMed
6.
go back to reference von Minckwitz G, Costa SD, Raab G, Blohmer JU, Eidtmann H, Hilfrich J, et al. Dose-dense doxorubicin, docetaxel, and granulocyte colony-stimulating factor support with or without tamoxifen as preoperative therapy in patients with operable carcinoma of the breast: a randomized, controlled, open phase IIb study. J Clin Oncol. 2001;19:3506–15. von Minckwitz G, Costa SD, Raab G, Blohmer JU, Eidtmann H, Hilfrich J, et al. Dose-dense doxorubicin, docetaxel, and granulocyte colony-stimulating factor support with or without tamoxifen as preoperative therapy in patients with operable carcinoma of the breast: a randomized, controlled, open phase IIb study. J Clin Oncol. 2001;19:3506–15.
7.
go back to reference Dieras V, Fumoleau P, Romieu G, Tubiana-Hulin M, Namer M, Mauriac L, et al. Randomized parallel study of doxorubicin plus paclitaxel and doxorubicin plus cyclophosphamide as neoadjuvant treatment of patients with breast cancer. J Clin Oncol. 2004;22:4958–65.CrossRefPubMed Dieras V, Fumoleau P, Romieu G, Tubiana-Hulin M, Namer M, Mauriac L, et al. Randomized parallel study of doxorubicin plus paclitaxel and doxorubicin plus cyclophosphamide as neoadjuvant treatment of patients with breast cancer. J Clin Oncol. 2004;22:4958–65.CrossRefPubMed
8.
go back to reference Buzdar AU. Preoperative chemotherapy treatment of breast cancer—a review. Cancer. 2007;110:2394–407.CrossRefPubMed Buzdar AU. Preoperative chemotherapy treatment of breast cancer—a review. Cancer. 2007;110:2394–407.CrossRefPubMed
9.
go back to reference von Minckwitz G, Untch M, Blohmer JU, Costa SD, Eidtmann H, Fasching PA, et al. Definition and impact of pathologic complete response on prognosis after neoadjuvant chemotherapy in various intrinsic breast cancer subtypes. J Clin Oncol. 2012;30:1796–804.CrossRef von Minckwitz G, Untch M, Blohmer JU, Costa SD, Eidtmann H, Fasching PA, et al. Definition and impact of pathologic complete response on prognosis after neoadjuvant chemotherapy in various intrinsic breast cancer subtypes. J Clin Oncol. 2012;30:1796–804.CrossRef
10.
go back to reference Carey LA, Dees EC, Sawyer L, Gatti L, Moore DT, Collichio F, et al. The triple negative paradox: primary tumor chemosensitivity of breast cancer subtypes. Clin Cancer Res. 2007;13:2329–34.CrossRefPubMed Carey LA, Dees EC, Sawyer L, Gatti L, Moore DT, Collichio F, et al. The triple negative paradox: primary tumor chemosensitivity of breast cancer subtypes. Clin Cancer Res. 2007;13:2329–34.CrossRefPubMed
11.
go back to reference Liedtke C, Mazouni C, Hess KR, Andre F, Tordai A, Mejia JA, et al. Response to neoadjuvant therapy and long-term survival in patients with triple-negative breast cancer. J Clin Oncol. 2008;26:1275–81.CrossRefPubMed Liedtke C, Mazouni C, Hess KR, Andre F, Tordai A, Mejia JA, et al. Response to neoadjuvant therapy and long-term survival in patients with triple-negative breast cancer. J Clin Oncol. 2008;26:1275–81.CrossRefPubMed
12.
go back to reference Toi M, Nakamura S, Kuroi K, Iwata H, Ohno S, Masuda N, et al. Phase II study of preoperative sequential FEC and docetaxel predicts of pathological response and disease free survival. Breast Cancer Res Treat. 2008;110:531–9.CrossRefPubMed Toi M, Nakamura S, Kuroi K, Iwata H, Ohno S, Masuda N, et al. Phase II study of preoperative sequential FEC and docetaxel predicts of pathological response and disease free survival. Breast Cancer Res Treat. 2008;110:531–9.CrossRefPubMed
13.
go back to reference Goldhirsch A, Winer EP, Coates AS, Gelber RD, Piccart-Gebhart M, Thurlimann B, et al. Personalizing the treatment of women with early breast cancer: highlights of the St. Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2013. Ann Oncol. 2013;24:2206–23.CrossRefPubMedPubMedCentral Goldhirsch A, Winer EP, Coates AS, Gelber RD, Piccart-Gebhart M, Thurlimann B, et al. Personalizing the treatment of women with early breast cancer: highlights of the St. Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2013. Ann Oncol. 2013;24:2206–23.CrossRefPubMedPubMedCentral
14.
go back to reference Cortazar P, Zhang L, Untch M, Mehta K, Costantino JP, Wolmark N, et al. Pathological complete response and long-term clinical benefit in breast cancer: the CTNeoBC pooled analysis. Lancet. 2014;384:164–72.CrossRefPubMed Cortazar P, Zhang L, Untch M, Mehta K, Costantino JP, Wolmark N, et al. Pathological complete response and long-term clinical benefit in breast cancer: the CTNeoBC pooled analysis. Lancet. 2014;384:164–72.CrossRefPubMed
15.
go back to reference Fujii T, Le Du F, Xiao L, Kogawa T, Carlos H, et al. Effectiveness of an adjuvant chemotherapy regimen for early-stage breast cancer: a systematic review and network meta-analysis. JAMA Oncol. 2015;1(9):1311–18.CrossRefPubMed Fujii T, Le Du F, Xiao L, Kogawa T, Carlos H, et al. Effectiveness of an adjuvant chemotherapy regimen for early-stage breast cancer: a systematic review and network meta-analysis. JAMA Oncol. 2015;1(9):1311–18.CrossRefPubMed
16.
go back to reference Takabatake D, Taira N, Hara F, Sien T, Kiyoto S, Takashima S, et al. Feasibility study of docetaxel with cyclophosphamide as adjuvant chemotherapy for Japanese breast cancer patients. Jpn J Clin Oncol. 2009;39:478–83.CrossRefPubMed Takabatake D, Taira N, Hara F, Sien T, Kiyoto S, Takashima S, et al. Feasibility study of docetaxel with cyclophosphamide as adjuvant chemotherapy for Japanese breast cancer patients. Jpn J Clin Oncol. 2009;39:478–83.CrossRefPubMed
17.
Metadata
Title
Docetaxel and cyclophosphamide as neoadjuvant chemotherapy in HER2-negative primary breast cancer
Authors
Katsuhiko Nakatsukasa
Hiroshi Koyama
Yoshimi Oouchi
Seiichi Imanishi
Naruhiko Mizuta
Kouichi Sakaguchi
Yoshifumi Fujita
Ikuya Fujiwara
Tatsuya Kotani
Takayuki Matsuda
Kenichirou Fukuda
Midori Morita
Sadao Kawakami
Yayoi Kadotani
Eiichi Konishi
Akio Yanagisawa
Tetsuya Taguchi
Publication date
01-01-2017
Publisher
Springer Japan
Published in
Breast Cancer / Issue 1/2017
Print ISSN: 1340-6868
Electronic ISSN: 1880-4233
DOI
https://doi.org/10.1007/s12282-016-0666-7

Other articles of this Issue 1/2017

Breast Cancer 1/2017 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine