title: High-dose chemotherapy with autologous stem-cell support as adjuvant therapy in breast cancer: overview of 15 randomized trials.
abstract: OBJECTIVE
  Adjuvant high-dose chemotherapy (HDC) with autologous hematopoietic stem-cell transplantation (AHST) for high-risk primary breast cancer has not been shown to prolong survival. Individual trials have had limited power to show overall benefit or benefits within subsets.
  
  
  METHODS
  We assembled individual patient data from 15 randomized trials that compared HDC versus control therapy without stem-cell support. Prospectively defined primary end points were relapse-free survival (RFS) and overall survival (OS). We compared the effect of HDC versus control by using log-rank tests and proportional hazards regression, and we adjusted for clinically relevant covariates. Subset analyses were by age, number of positive lymph nodes, tumor size, histology, hormone receptor (HmR) status, and human epidermal growth factor receptor 2 (HER2) status.
  
  
  RESULTS
  Of 6,210 total patients (n = 3,118, HDC; n = 3,092 control), the median age was 46 years; 69% were premenopausal, 29% were postmenopausal, and 2% were unknown menopausal status; 49.5% were HmR positive; 33.5% were HmR negative, and 17% were unknown HmR status. The median follow-up was 6 years. After analysis was adjusted for covariates, HDC was found to prolong relapse-free survival (RFS; hazard ratio [HR], 0.87; 95% CI, 0.81 to 0.93; P < .001) but not overall survival (OS; HR, 0.94; 95% CI, 0.87 to 1.02; P = .13). For OS, no covariates had statistically significant interactions with treatment effect, and no subsets evinced a significant effect of HDC. Younger patients had a significantly better RFS on HDC than did older patients.
  
  
  CONCLUSIONS
  Adjuvant HDC with AHST prolonged RFS in high-risk primary breast cancer compared with control, but this did not translate into a significant OS benefit. Whether HDC benefits patients in the context of targeted therapies is unknown.
authors.affiliation: Division of Quantitative Sciences, Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX 77230-1402, USA. dberry@mdanderson.org
authors.forename: Donald A
authors.initials: DA
authors.lastname: Berry
authors.forename: Naoto T
authors.initials: NT
authors.lastname: Ueno
authors.forename: Marcella M
authors.initials: MM
authors.lastname: Johnson
authors.forename: Xiudong
authors.initials: X
authors.lastname: Lei
authors.forename: Jean
authors.initials: J
authors.lastname: Caputo
authors.forename: Sjoerd
authors.initials: S
authors.lastname: Rodenhuis
authors.forename: William P
authors.initials: WP
authors.lastname: Peters
authors.forename: Robert C
authors.initials: RC
authors.lastname: Leonard
authors.forename: William E
authors.initials: WE
authors.lastname: Barlow
authors.forename: Martin S
authors.initials: MS
authors.lastname: Tallman
authors.forename: Jonas
authors.initials: J
authors.lastname: Bergh
authors.forename: Ulrike A
authors.initials: UA
authors.lastname: Nitz
authors.forename: Alessandro M
authors.initials: AM
authors.lastname: Gianni
authors.forename: Russell L
authors.initials: RL
authors.lastname: Basser
authors.forename: Axel R
authors.initials: AR
authors.lastname: Zander
authors.forename: R Charles
authors.initials: RC
authors.lastname: Coombes
authors.forename: Henri
authors.initials: H
authors.lastname: Roché
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Tokuda
authors.forename: Elisabeth G E
authors.initials: EG
authors.lastname: de Vries
authors.forename: Gabriel N
authors.initials: GN
authors.lastname: Hortobagyi
authors.forename: John P
authors.initials: JP
authors.lastname: Crown
authors.forename: Paolo
authors.initials: P
authors.lastname: Pedrazzoli
authors.forename: Marco
authors.initials: M
authors.lastname: Bregni
authors.forename: Taner
authors.initials: T
authors.lastname: Demirer
mesh_terms: D000328:Adult; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001943:Breast Neoplasms / Q000188:drug therapy / Q000401:mortality / Q000628:therapy*; D017024:Chemotherapy, Adjuvant; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008875:Middle Aged; D016609:Neoplasms, Second Primary; D016032:Randomized Controlled Trials as Topic; D014182:Transplantation, Autologous
chemical_list: D000970:Antineoplastic Agents