title: Prognostic factors for prolonged progression-free survival with high-dose chemotherapy with autologous stem-cell support for advanced breast cancer.
abstract: OBJECTIVE
  With a median observation time of 50 months from transplant, 13 (22%) of 62 women with metastatic breast cancer treated with high-dose chemotherapy at the Dana-Farber Cancer Institute (DFCI)/Beth Israel Hospital (BIH) remain progression-free. This study determined factors prognostic for prolonged progression-free survival (PFS).
  
  
  METHODS
  From June 1988 to January 1992, women who responded to standard chemotherapy received high-dose cyclophosphamide, thiotepa, and carboplatin with autotransplantation. Data encompassing initial breast cancer diagnosis, metastatic presentation, and response to induction treatment were examined for correlations with improved PFS.
  
  
  RESULTS
  The 5-year PFS rate for the entire group is estimated to be 21% (95% confidence interval [CI], 10% to 32%). For those patients who attained a complete response (CR) to induction therapy, the 5-year PFS rate is estimated to be 31% (95% CI, 0% to 63%). In univariate analyses, a single metastatic site, CR to induction therapy, prolonged interval from primary diagnosis to first metastases, estrogen receptor (ER)-negative tumors, and older age (> or = 40 years) were associated with prolonged PFS. In multivariate analyses, single metastatic site (P = .002) and attainment of a CR to induction chemotherapy (P = .04) were the most significant predictors for PFS, with a strong trend observed for an interval from primary diagnosis to onset of metastatic disease of 24+ months (P = .066).
  
  
  CONCLUSIONS
  We and others have shown that 10% to 25% of women with metastatic breast cancer are progression-free after high-dose chemotherapy with autotransplantation. Those with chemosensitive disease, minimal tumor bulk, and a prolonged disease-free interval appear to benefit most. Emphasis should continue to focus on the development of more effective cytotoxic regimens and biologic approaches to increase the percentage of patients who may benefit from this approach.
authors.affiliation: Dana-Farber Cancer Institute, Beth Israel Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: L J
authors.initials: LJ
authors.lastname: Ayash
authors.forename: C
authors.initials: C
authors.lastname: Wheeler
authors.forename: D
authors.initials: D
authors.lastname: Fairclough
authors.forename: G
authors.initials: G
authors.lastname: Schwartz
authors.forename: E
authors.initials: E
authors.lastname: Reich
authors.forename: D
authors.initials: D
authors.lastname: Warren
authors.forename: L
authors.initials: L
authors.lastname: Schnipper
authors.forename: K
authors.initials: K
authors.lastname: Antman
authors.forename: E
authors.initials: E
authors.lastname: Frei
authors.forename: A
authors.initials: A
authors.lastname: Elias
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016026:Bone Marrow Transplantation; D001943:Breast Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000628:therapy*; D016190:Carboplatin / Q000008:administration & dosage; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage; D018572:Disease-Free Survival; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008875:Middle Aged; D015999:Multivariate Analysis; D009362:Neoplasm Metastasis; D011379:Prognosis; D016016:Proportional Hazards Models; D012074:Remission Induction; D013852:Thiotepa / Q000008:administration & dosage; D014182:Transplantation, Autologous
chemical_list: D003520:Cyclophosphamide; D013852:Thiotepa; D016190:Carboplatin