High dose chemotherapy for breast cancer: the case for trials in adjuvant therapy

Adjuvant polychemotherapy reduces the annual mortality for breast cancer, the effect being seen for at least the first decade after primary treatment for stage II disease. However, the overall benefit is modest with an annual reduction in the odds of death of the order of 20%-30%. For patients at standard or low risk of recurrence this appears to be an acceptable benefit given low toxicity of treatment. However, some patients have a very much worse prognosis identifiable on the basis of the number of involved axillary nodes at surgery. Patients with more than 10 lymph nodes, for example, have a predicted survival of less than 30% at 5 years and around 10% at 10 years. High dose chemotherapy has shown immediate benefits in terms of complete response rates in advanced breast cancer. Potential benefits of this treatment could be even higher in the adjuvant setting given the patient's fitness and the fact that micrometastatic disease represents the best clinical analogue of the successful laboratory experimental conditions. Now that the safety factors appear to be favourable with a treatment-related mortality of less than 5% it would appear that stage II poor risk disease is an appropriate setting to test high dose chemotherapy against the best conventional therapy in randomized trials.