Is chemotherapy alone adequate for young women with oestrogen-receptor-positive breast cancer?

Lancet. 2000 May 27;355(9218):1869-74. doi: 10.1016/s0140-6736(00)02292-3.


Background: The prognosis of breast cancer in very young women is generally considered to be unfavourable. Therefore, the outcome of adjuvant therapy was analysed in a population of young (<35 years) premenopausal patients treated in four randomised controlled trials.

Methods: Between 1978 and 1993 the International Breast Cancer Study Group (IBCSG) treated 3700 premenopausal and perimenopausal patients with various timing and duration of adjuvant cyclophosphamide, methotrexate, and fluorouracil (CMF with or without low-dose prednisone and oophorectomy). 314 of these women were less than 35 years old at randomisation.

Findings: Relapse and death occurred earlier and more often in younger (<35 years) than in older (> or = 35) patients with a 10 year disease-free survival of 35% (SE 3) versus 47% (1) (hazard ratio 1.41 [95% CI 1.22-1.62], p<0.001) and overall survival of 49% (3) versus 62% (1) (1.50 [1.28-1.77], p<0.001). Younger patients with oestrogen-receptor positive tumours had a significantly worse disease-free survival than younger patients with oestrogen-receptor negative tumours. By contrast, among older patients the disease-free survival was similar irrespective of oestrogen-receptor status.

Interpretation: Young premenopausal breast cancer patients treated with adjuvant CMF chemotherapy had higher risk of relapse and death than older premenopausal patients, especially if their tumours expressed oestrogen receptors. The endocrine effects of chemotherapy alone are insufficient for the younger age group and these patients should strongly consider additional endocrine therapies (tamoxifen or ovarian ablation) if their tumours express oestrogen receptors.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Adult
  • Age Factors
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / mortality
  • Chemotherapy, Adjuvant
  • Combined Modality Therapy
  • Cyclophosphamide / administration & dosage
  • Disease-Free Survival
  • Female
  • Fluorouracil / administration & dosage
  • Humans
  • Methotrexate / administration & dosage
  • Multicenter Studies as Topic
  • Ovariectomy
  • Prednisone / administration & dosage
  • Premenopause
  • Prognosis
  • Randomized Controlled Trials as Topic
  • Receptors, Estrogen / metabolism*
  • Risk Factors


  • Receptors, Estrogen
  • Cyclophosphamide
  • Fluorouracil
  • Prednisone
  • Methotrexate

Supplementary concepts

  • CMF regimen