Factors predicting long-term survival for metastatic breast cancer patients treated with high-dose chemotherapy and bone marrow support

Cancer. 1994 Apr 15;73(8):2157-67. doi: 10.1002/1097-0142(19940415)73:8<2157::aid-cncr2820730821>3.0.co;2-1.


Background: Poor prognosis of Stage IV breast cancer patients have at best a 10% 3-year survival rate with conventional chemotherapy. Dose-intensive chemotherapy improved survival rates for some of these patients.

Methods: All patients were Stage IV estrogen receptor-negative or estrogen receptor-positive hormonal refractory and received conventional chemotherapy (induction phase) to the point of achieving maximal response; if disease was stable or the patients responded, they entered high-dose chemotherapy (intensive phase). Seventy-six percent of the patients received two high-dose treatments with cyclophosphamide (4.5-6.0 g/m2), etoposide (750-1500 mg/m2), and cisplatin (120-180 mg/m2). Patients were randomized to receive or not receive autologous marrow. To identify prognostic factors for survival, univariate statistical analysis and multivariate models were applied to patient subsets.

Results: Univariate analysis identified a number of factors whose presence indicates improvement in overall survival rates. These include: (1) absence of liver relapse (P = 0.001); (2) absence of soft tissue relapse (P = 0.001); (3) a smaller number of metastatic sites at the time of detecting Stage IV disease (P = 0.026); and (4) disease-free interval greater than 1 year from initial diagnosis to Stage IV disease (P = 0.011). Multivariate models were fitted to the data, and three variables were identified as independent negative predictors for overall survival: (1) liver site (P = 0.001); (2) soft tissue site (P = 0.039); and (3) prior adjuvant chemotherapy (P = 0.028).

Conclusions: Shorter survival after high-dose chemotherapy is predicted independently by patients pretreated with adjuvant chemotherapy, by disease distributed to the liver or the soft tissue.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Analysis of Variance
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Bone Marrow Transplantation*
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / therapy*
  • Breast Neoplasms / ultrastructure
  • Cisplatin / administration & dosage
  • Combined Modality Therapy
  • Cyclophosphamide / administration & dosage
  • Dose-Response Relationship, Drug
  • Etoposide / administration & dosage
  • Female
  • Follow-Up Studies
  • Humans
  • Middle Aged
  • Neoplasm Metastasis
  • Neoplasm Staging
  • Neoplasms, Hormone-Dependent / drug therapy
  • Neoplasms, Hormone-Dependent / therapy*
  • Neoplasms, Hormone-Dependent / ultrastructure
  • Prognosis
  • Proportional Hazards Models
  • Receptors, Estrogen / physiology
  • Risk Factors


  • Receptors, Estrogen
  • Etoposide
  • Cyclophosphamide
  • Cisplatin