title: 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: 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/m(2)) and C (500 mg/m(2)) 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Breast and Endocrine Surgery, Okayama University Hospital, Okayama, 700-8558, Japan, tshien@md.okayama-u.ac.jp.
authors.forename: Tadahiko
authors.initials: T
authors.lastname: Shien
authors.forename: Hiroji
authors.initials: H
authors.lastname: Iwata
authors.forename: Kenjiro
authors.initials: K
authors.lastname: Aogi
authors.forename: Takashi
authors.initials: T
authors.lastname: Fukutomi
authors.forename: Kenichi
authors.initials: K
authors.lastname: Inoue
authors.forename: Takayuki
authors.initials: T
authors.lastname: Kinoshita
authors.forename: Masato
authors.initials: M
authors.lastname: Takahashi
authors.forename: Akira
authors.initials: A
authors.lastname: Matsui
authors.forename: Taro
authors.initials: T
authors.lastname: Shibata
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Fukuda
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D017024:Chemotherapy, Adjuvant / Q000379:methods; D003520:Cyclophosphamide / Q000008:administration & dosage; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D006801:Humans; D007564:Japan; D008207:Lymphatic Metastasis / Q000473:pathology; D008495:Medical Oncology; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000473:pathology; D017698:Postmenopause; D011960:Receptors, Estrogen / Q000235:genetics; D013629:Tamoxifen / Q000008:administration & dosage
chemical_list: D011960:Receptors, Estrogen; D013629:Tamoxifen; D004317:Doxorubicin; D003520:Cyclophosphamide