Dose-response effect of adjuvant chemotherapy in breast cancer

N Engl J Med. 1981 Jan 1;304(1):10-5. doi: 10.1056/NEJM198101013040103.


We retrospectively analyzed the role of the dose level of CMF (cyclophosphamide, methotrexate, and fluorouracil) in postoperative adjuvant chemotherapy for breast cancer and in chemotherapy for metastatic breast cancer. There was a clear dose-response effect, indicating that CMF was useful only when given in a full or nearly full dose (greater than or equal to 85 per cent of the planned dose). Those given adjuvant therapy with 12 cycles of CMF at this dose level had a five-year relapse-free survival of 77 per cent, as compared with 45 per cent of patients treated only with radical mastectomy (P = 0.0001). In contrast, a subgroup receiving less than 65 per cent of the planned dose had a five-year survival without relapses of 48 per cent and a five-year survival with relapses of 67 per cent. These results are similar to those observed in a control group. With each dose level, the results at five years were influenced by the number of axillary lymph nodes involved but not by menopausal status. Our findings indicate that it is necessary to administer combination chemotherapy at a full dose to achieve clinical benefit.

Publication types

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

MeSH terms

  • Aged
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / mortality
  • Breast Neoplasms / surgery
  • Cyclophosphamide / administration & dosage*
  • Cyclophosphamide / therapeutic use
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Drug Therapy, Combination
  • Female
  • Fluorouracil / administration & dosage*
  • Fluorouracil / therapeutic use
  • Follow-Up Studies
  • Humans
  • Mastectomy
  • Menopause
  • Methotrexate / administration & dosage*
  • Methotrexate / therapeutic use
  • Middle Aged
  • Neoplasm Metastasis


  • Cyclophosphamide
  • Fluorouracil
  • Methotrexate