title: High-dose chemotherapy for high-risk primary and metastatic breast cancer: is another look warranted?
abstract: OBJECTIVE
  The controversy surrounding high-dose chemotherapy (HDC) for breast cancer seems to have given place to skepticism about its efficacy, regardless of regimen or schedule, for any subset of patients with high-risk primary breast cancer (HRPBC) or metastatic disease. We review here the main publications in this field since 2006, focusing on updates of randomized trials comparing HDC with standard-dose chemotherapy.
  
  
  RESULTS
  A meta-analysis of all 15 randomized HRPBC trials (n = 6102) has detected an absolute 13% event-free survival benefit in favor of HDC (P = 0.0001) at a median 6-year follow-up. The absolute differences in breast cancer-specific (7%) and overall survival (5%) did not reach statistical significance. Several retrospective subset analyses suggest that HDC may be particularly effective among patients with HER2-negative tumors, particularly if also hormone receptor negative (triple negative).
  
  
  CONCLUSIONS
  A global event-free survival advantage favoring HDC has been shown in HRPBC trials, which seems to affect particularly patients with triple negative tumors. Event-free survival is a clinically relevant endpoint in the adjuvant setting, in which the goal of any treatment should be cure. Therefore, it seems that the current broad skepticism about HDC is unduly dismissive of this benefit. HDC remains a valid research strategy in appropriate subpopulations such as triple-negative HRPBC or oligometastatic disease.
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 423, Houston, TX 77030, USA. ynieto@mdanderson.org
authors.forename: Yago
authors.initials: Y
authors.lastname: Nieto
authors.forename: Elizabeth J
authors.initials: EJ
authors.lastname: Shpall
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality / Q000556:secondary*; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D015201:Meta-Analysis as Topic; D016032:Randomized Controlled Trials as Topic; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics
chemical_list: D000970:Antineoplastic Agents; D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human