Controversial issues in adjuvant systemic therapy of early breast cancer.

Although it has been shown that adequate local therapy of primary breast cancer decreases the risk of distant failure and death due to the disease, treatment results with local therapy alone are clearly inadequate with c. 30-40% of patients developing a disease recurrence within the first ten years after primary diagnosis. In the past 10-15 years there has been significant progress in the field of systemic adjuvant therapy of breast cancer. It is now reliably established that the concept is valid; that is, that early treatment with either cytotoxic chemotherapy or endocrine therapy does result in improved survival compared with treatment deferred until relapse. Despite considerable progress, several controversial issues remain. These include the optimal timing and sequencing of treatment, optimal drug doses, and the role of new drugs such as taxanes and new endocrine agents. The identification of more powerful prognostic and/or predictive tests might have substantial clinical implications but major breakthroughs in this field of research are still to come. A relatively new and important issue in clinical decision-making regarding the use of different adjuvant therapies is long-term toxicity such as leukemia with some types of chemotherapy and endometrial cancer (and possibly other malignancies) with long-term tamoxifen. Further progress in the field of adjuvant therapy of breast cancer continues to rely on well-designed, prospective, controlled clinical trials and overviews of such studies.