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)

Abstract

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. 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/m(2)) and C (500 mg/m(2)) plus TAM (ACT) as adjuvant therapy following surgery. 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. 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.