Conventional adjuvant chemotherapy with or without high-dose chemotherapy and autologous stem-cell transplantation in high-risk breast cancer

N Engl J Med. 2003 Jul 3;349(1):17-26. doi: 10.1056/NEJMoa030684.

Abstract

Background: The prognosis for women with primary breast cancer and 10 or more involved axillary lymph nodes is poor. High-dose chemotherapy with autologous hematopoietic stem-cell transplantation has been reported to be effective in the adjuvant setting for patients at high risk for relapse.

Methods: We randomly assigned 540 female patients with primary breast cancer and at least 10 involved ipsilateral axillary lymph nodes to receive either six cycles of adjuvant chemotherapy with cyclophosphamide, doxorubicin, and fluorouracil (CAF) or the same adjuvant chemotherapy followed by high-dose chemotherapy with cyclophosphamide and thiotepa and autologous hematopoietic stem-cell transplantation.

Results: Among the 511 eligible patients, there was no significant difference in disease-free survival, overall survival, or the time to recurrence between those who received CAF alone and those who received CAF plus high-dose chemotherapy and stem-cell transplantation. Among 417 patients fulfilling strict eligibility criteria, the time to recurrence was longer for patients who underwent stem-cell transplantation than for those who received CAF alone. In the transplantation group, nine patients died of transplantation-related complications and a myelodysplastic syndrome or acute myeloid leukemia developed in nine.

Conclusions: The addition of high-dose chemotherapy and autologous hematopoietic stem-cell transplantation to six cycles of adjuvant chemotherapy with CAF may reduce the risk of relapse but does not improve the outcome among patients with primary breast cancer and at least 10 involved axillary lymph nodes. Conventional-dose adjuvant chemotherapy remains the standard of care for such patients.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / mortality
  • Breast Neoplasms / therapy
  • Chemotherapy, Adjuvant
  • Cyclophosphamide / administration & dosage
  • Disease-Free Survival
  • Doxorubicin / administration & dosage
  • Female
  • Fluorouracil / administration & dosage
  • Hematopoietic Stem Cell Transplantation* / adverse effects
  • Humans
  • Lymphatic Metastasis
  • Middle Aged
  • Neoplasm Recurrence, Local / prevention & control
  • Prognosis
  • Survival Analysis
  • Tamoxifen / administration & dosage
  • Thiotepa / administration & dosage
  • Transplantation, Autologous

Substances

  • Tamoxifen
  • Doxorubicin
  • Cyclophosphamide
  • Thiotepa
  • Fluorouracil