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Tamoxifen versus tamoxifen plus doxorubicin and cyclophosphamide as adjuvant therapy for node-positive postmenopausal breast cancer: results of a Japan Clinical Oncology Group Study (JCOG9401)

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Abstract

Background

Cancer subtype has recently become an increasingly important consideration when deciding the treatment strategy for breast cancer. For the estrogen receptor positive (ER+) subtype, the efficacy of adjuvant endocrine therapy is definitive, but that of adjuvant chemotherapy is controversial.

Methods

In order to evaluate the effect of adding doxorubicin (A) and cyclophosphamide (C) to tamoxifen (TAM) (ACT) on the overall survival (OS) of node-positive postmenopausal breast cancer (PMBC) patients, we conducted a randomized trial. Eligibility criteria included pathologically node-positive (n = 1–9) PMBC, stage I–IIIA disease. Patients were randomized to receive either TAM (20 mg daily) for 2 years or A (40 mg/m2) and C (500 mg/m2) plus TAM (ACT) as adjuvant therapy following surgery.

Results

One hundred twenty-nine patients were recruited (TAM 64, ACT 65) between October 1994 and July 1999. The hazard ratios for OS and relapse-free survival (RFS) were 0.58 (95 % CI 0.24–1.39; log-rank p = 0.22) and 0.45 (95 %CI 0.24–0.86; log-rank p = 0.013), respectively, in favor of ACT. The 5-year OS and RFS were 76.9 % (ER+ 87.1 %, ER− 53.3 %) and 54.9 % (ER+ 59.3 %, ER− 42.9 %) for TAM and 85.0 % (ER+ 90.0 %, ER− 77.1 %) and 76.7 % (ER+ 76.9 %, ER− 76.0 %) for ACT. A higher proportion of the patients receiving ACT than those receiving TAM experienced grade 3 decreased white blood cell count and grade 2–3 nausea.

Conclusion

The efficacy of adding AC to TAM was not high for ER+, node-positive PMBC. However, adjuvant ACT therapy was considered to be effective for ER−, node-positive PMBC.

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Acknowledgments

We thank Ms. Kyoko Minamoto and Kazumi Kubota for data management, Dr. Naoki Ishizuka and Mr. Junki Mizusawa for statistical analyses, and Dr. Kenichi Nakamura for the preparation of the manuscript. This study was supported by a National Cancer Center Research and Development Fund (23-A-16 and 23-A-17) and Grants-in-Aid for Cancer Research (5S-1, 8S-1, 11S-1, 11S-4, 14S-1, 14S-4, 17S-1, 17S-5, 20S-1 and 20S-6) from the Ministry of Health, Labour and Welfare, Japan.

Conflict of interest

Hiroji Iwata received honoraria for speaking events from Chugai Pharmaceutical Co., Ltd. Tadahiko Shien, Kenjiro Aogi, Takashi Fukutomi, Kenichi Inoue, Takayuki Kinoshita, Masato Takahashi, Akira Matsui, Taro Shibata, Haruhiko Fukuda had no conflicts of interest.

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Correspondence to Tadahiko Shien.

Additional information

On behalf of the JCOG Breast Cancer Study Group. The 22 institutions that belong to the JCOG Breast Cancer Study Group are listed in Appendix.

Appendix: Participating institutions (from north to south)

Appendix: Participating institutions (from north to south)

The 22 institutions that belonged to the JCOG Breast Cancer Study Group and participated in this trial are as follows: National Sapporo Hospital, International Medical Center of Japan, Tochigi Cancer Center, Metropolitan Komagome Hospital, National Cancer Center, National Cancer Center East, Tokai University Hospital, National Atami Hospital, Hamamatsu Medical Center, Aichi Cancer Center, Osaka National Hospital, Kinki University Hospital, National Shikoku Cancer Center, National Kure Medical Center, National Nagasaki Medical Center, Saitama Cancer Center, St Luke’s International Hospital, Hyogo Medical Center, Shizuoka Cancer Center, Niigata Cancer Center Hospital, Kawasaki Medical School Hospital, and Kitakyushu Municipal Medical Center.

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Shien, T., Iwata, H., Aogi, K. et al. Tamoxifen versus tamoxifen plus doxorubicin and cyclophosphamide as adjuvant therapy for node-positive postmenopausal breast cancer: results of a Japan Clinical Oncology Group Study (JCOG9401). Int J Clin Oncol 19, 982–988 (2014). https://doi.org/10.1007/s10147-013-0657-z

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  • DOI: https://doi.org/10.1007/s10147-013-0657-z

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