Adjuvant Therapy for Early Breast Cancer: A Time to Refine

Adjuvant endocrine therapy and chemotherapy are now being used extensively to treat primary breast cancer and are probably beginning to have an impact on national mortality data in the U.K. ( 1 , 2 ). The main difficulty at present is identifying those patients who may require such treatment. The widespread use and evaluation of adjuvant combination chemotherapy started in 1976 after Bonadonna et al. ( 3 ) reported the results of an innovative trial using cyclophosphamide, methotrexate, and fluorouracil (CMF) after mastectomy for the treatment of patients with axillary lymph node-positive primary breast cancer. Their results showed that such treatment could substantially reduce the risk of relapse. Many trials have since confirmed these initial results, and, in 1985, an overview metaanalysis of these trials ( 4 ) showed a statistically significant reduction in mortality for women under the age of 50 years who were given adjuvant combination chemotherapy. Similarly, early trials of endocrine therapy using ovarian ablation had shown reductions in the rates of relapse ( 5 , 6 ) and were followed in 1977 by the start of the NATO (Nolvadex Adjuvant Trial Organization) trial of adjuvant tamoxifen, which subsequently showed that tamoxifen given for 2 years after mastectomy reduced the risk of relapse and death ( 7 ). Since then, other trials have shown similar results, and the 1985 overview ( 4 ) confirmed that there was a significant reduction in mortality in women aged 50 years or older who received adjuvant tamoxifen.