After several decades in which the scope and intensity of regional therapies increased, without a corresponding increase in cure rates, attention has turned to systemic treatments. Adjuvant therapy for carcinoma is use in an attempt to destroy micrometastases thus preventing the development of clinical metastases. Initial results have been encouraging and an understanding of tumor cell kinetics has led to the use of better schedules and combinations of drugs that have substantially decreased the probability or treatment failure and prolonged survival compared with the results of operation alone.
Good clinical judgment requires a balanced assessment of both a therapy's benefits and its costs, especially in terms of toxicity, in each patient. During early clinical evaluation of a new therapy, the toxic effects may be obvious and the benefits uncertain. As a result, both physician and patient may be understandably reluctant to use the therapy or even to participate in the experiment. After the first report of benefit, on the other hand, there is a danger that the new therapy may be used for every affected patient without due regard for toxicity. Many physicians have leaned alternately toward one . . .
Systemic therapy for operable breast cancer can delay the time to recurrence. Recurrence of breast cancer can follow a variable clinical course but will lead to death in virtually all cases. This delay is reflected in an accompanying improvement in overall survival with treatment. Almost 35 years have passed since the introduction of adjuvant chemotherapy, whereas adjuvant tamoxifen trials were begun 17 years ago. In that time, only in a minority of patients has a clear consensus emerged on the appropriate use of adjuvant therapies. Overview analysis from large numbers of controlled clinical trials has produced a much larger data base for examining the effects of hormonal and cytotoxic therapy on the outcome of patients with early-stage breast cancer and provides greater statistical power to detect small differences in particular subgroups of patients, which may not have been apparent in individual studies. Patients with involved lymph nodes are now routinely treated with chemotherapy if they are premenopausal and with tamoxifen if they are postmenopausal, especially if their tumors contain estrogen receptor. More recent trials attempt to examine the use of these therapies outside of these prescribed groups as well as the introduction of new chemotherapeutic agents and dosage regimens, some of which are based on biologic principles of alternating, non-cross-resistant therapy and dose responsiveness. Treatment of node-negative breast cancer remains controversial. Small but real differences in odds of relapse have emerged with adjuvant treatment, although the nature of the risks and benefits remains to be defined.