Randomized trial of low-dose chemotherapy added to tamoxifen in patients with receptor-positive and lymph node-positive breast cancer

J Clin Oncol. 1999 Jun;17(6):1701-9. doi: 10.1200/JCO.1999.17.6.1701.

Abstract

Purpose: To evaluate the outcome in patients with stage II hormone receptor-positive breast cancer treated or not treated with low-dose, short-term chemotherapy in addition to tamoxifen in terms of disease-free and overall survival.

Patients and methods: A total of 613 patients were randomized to receive either low-dose chemotherapy (doxorubicin 20 mg/m(2) and vincristine 1 mg/m(2) on day 1; cyclophosphamide 300 mg/m(2); methotrexate 25 mg/m(2); and fluorouracil 600 mg/m(2) on days 29 and 36 intravenously) or no chemotherapy in addition to 20 mg of tamoxifen orally for 2 years. A third group without any treatment (postmenopausal patients only) was terminated after the accrual of 79 patients due to ethical reasons.

Results: After a median follow-up period of 7.5 years, the addition of chemotherapy did not improve the outcome in patients as compared with those treated with tamoxifen alone, neither with respect to disease-free nor overall survival. Multivariate analysis of prognostic factors for disease-free survival revealed menopausal status, in addition to nodal status, progesterone receptor, and histologic grade as significant. Both untreated postmenopausal and tamoxifen-treated premenopausal patients showed identical prognoses significantly inferior to the tamoxifen-treated postmenopausal cohort. Prognostic factors for overall survival in the multivariate analysis showed nodal and tumor stage, tumor grade, and hormone receptor level as significant.

Conclusion: Low-dose chemotherapy in addition to tamoxifen does not improve the prognosis of stage II breast cancer patients with hormone-responsive tumors. Tamoxifen-treated postmenopausal patients show a significantly better prognosis than premenopausal patients, favoring the hypothesis of a more pronounced effect of tamoxifen in the older age groups.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial

MeSH terms

  • Age Factors
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Breast Neoplasms / diagnosis
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / mortality
  • Carcinoma / diagnosis
  • Carcinoma / drug therapy*
  • Carcinoma / metabolism
  • Carcinoma / mortality
  • Cyclophosphamide / administration & dosage
  • Disease-Free Survival
  • Doxorubicin / administration & dosage
  • Female
  • Fluorouracil / administration & dosage
  • Humans
  • Lymphatic Metastasis
  • Methotrexate / administration & dosage
  • Middle Aged
  • Neoplasm Recurrence, Local
  • Prognosis
  • Receptors, Estrogen / metabolism
  • Receptors, Progesterone / metabolism
  • Recurrence
  • Survival Rate
  • Tamoxifen / administration & dosage
  • Tamoxifen / therapeutic use*
  • Vincristine / administration & dosage

Substances

  • Receptors, Estrogen
  • Receptors, Progesterone
  • Tamoxifen
  • Vincristine
  • Doxorubicin
  • Cyclophosphamide
  • Fluorouracil
  • Methotrexate

Supplementary concepts

  • CMFDV protocol