Adjuvant anthracycline-based chemotherapy for early breast cancer: do the dose and schedule matter?

The rationale to justify the use of anthracyclines as adjuvant therapy for breast cancer is their proven superiority over CMF. Indeed, this has been demonstrated by a number of randomised clinical trials and recently confirmed by the Oxford meta-analysis. Nevertheless, the absolute benefit is modest (on average 4%), and with the cost of increased toxicity. Interestingly, many individual trials were unable to confirm the role of anthracyclines in early breast cancer, though most of these were either underpowered to show such small differences, or had inappropriate experimental arms. On the other hand, several trials included in the meta-analysis also had inadequate control arms. So far, probably only three trials were able to individually confirm this benefit: the American INT 0102, the Canadian MA5 and more recently, the British NEAT/NCTBG. Numerous different anthracycline schedules have been used as adjuvant therapy, many of these having never been compared to CMF. Unfortunately, as research is moving towards other more important questions, many of these uncertainties may never be clarified. In this paper, we review the current evidence behind some of the most commonly used anthracycline schedules.