title: Randomized trial of high-dose chemotherapy and autologous hematopoietic stem cell support for high-risk primary breast carcinoma: follow-up at 12 years.
abstract: BACKGROUND
  The authors previously reported results from a randomized trial of standard-dose chemotherapy with combined 5-fluorouracil (1000 mg/m2 per cycle), doxorubicin (50 mg/m2 per cycle), and cyclophosphamide (500 mg/m2 per cycle) (FAC) versus FAC followed by high-dose chemotherapy (HDCT) and autologous stem cell support (ASCS) for patients with high-risk primary breast carcinoma. After a median follow-up of 6.5 years, no significant differences were observed in recurrence-free survival (RFS) or overall survival (OS) between the 2 arms. This report updates the survival analyses.
  
  
  METHODS
  Patients with >or=10 positive axillary lymph nodes after primary surgery or >or=4 positive lymph nodes at surgery after neoadjuvant chemotherapy were eligible. All patients were to receive 8 cycles of FAC. Patients were assigned randomly to receive either no further chemotherapy or 2 cycles of combined high-dose cyclophosphamide (5250 mg/m2 per cycle), etoposide (1200 mg/m2 per cycle), and cisplatin (165 mg/m2 per cycle) with ASCS. Primary endpoints were RFS and OS. RFS and OS were calculated by using the Kaplan-Meier method. The log-rank statistic was used to compare treatment arms.
  
  
  RESULTS
  Between 1990 and 1997, 78 patients were registered, and 39 patients were assigned randomly to each arm. The median follow-up for all patients who were alive at last follow-up was 142.5 months (range, 45-169 months). An intention-to-treat analysis showed no significant difference between the 2 arms in terms of RFS (at 10 years: 40% with FAC vs. 26% with FAC plus HDCT; P=.11) or OS (at 10 years: 47% with FAC vs. 42% with FAC plus HDCT; P=.13).
  
  
  CONCLUSIONS
  With a median follow-up of nearly 12 years for patients who remained alive, this trial continued to demonstrate no RFS or OS advantage for patients with high-risk primary breast carcinoma treated with HDCT after standard-dose FAC chemotherapy.
authors.affiliation: Department of Breast Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas.
authors.forename: Emer O
authors.initials: EO
authors.lastname: Hanrahan
authors.forename: Kristine
authors.initials: K
authors.lastname: Broglio
authors.forename: Deborah
authors.initials: D
authors.lastname: Frye
authors.forename: Aman U
authors.initials: AU
authors.lastname: Buzdar
authors.forename: Richard L
authors.initials: RL
authors.lastname: Theriault
authors.forename: Vicente
authors.initials: V
authors.lastname: Valero
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Booser
authors.forename: Sonja E
authors.initials: SE
authors.lastname: Singletary
authors.forename: Eric A
authors.initials: EA
authors.lastname: Strom
authors.forename: James L
authors.initials: JL
authors.lastname: Gajewski
authors.forename: Richard E
authors.initials: RE
authors.lastname: Champlin
authors.forename: Gabriel N
authors.initials: GN
authors.lastname: Hortobagyi
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D017024:Chemotherapy, Adjuvant; D002945:Cisplatin / Q000008:administration & dosage; D003520:Cyclophosphamide / Q000008:administration & dosage; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D005500:Follow-Up Studies; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D015996:Survival Rate; D014182:Transplantation, Autologous; D016896:Treatment Outcome
chemical_list: D005047:Etoposide; D003520:Cyclophosphamide; D002945:Cisplatin