Adjuvant chemotherapy in early breast cancer: optimal and suboptimal anthracycline-containing regimens

We hypothesized that the advantage of adjuvant anthracycline-containing regimens over the conventional CMF combination found by the Early Breast Cancer Trialists' Collaborative Group overview may depend on the 'additive' or 'substitutive' nature of the administration of anthracycline in the experimental arm. The aim of this study was to explore this hypothesis. By means of computerized and hand searches, we identified 21 published randomized trials comparing early breast cancer adjuvant chemotherapies with and without anthracycline, and divided them into those in which the use of anthracycline was substantially 'additive' or substantially 'substitutive'. The trial results were then judged 'positive' or 'negative' depending on whether they showed statistically significant differences in disease-free or overall survival in favor of the anthracycline-containing regimen. Anthracycline was substantially 'additive' in 14 trials, eight of which were 'positive', and substantially 'substitutive' in seven, all of which were 'negative': this difference is statistically significant (P = 0.018). In conclusion this trial classification, an attempt to test a very simple unifying concept with the aim of explaining the different results of trials involving the administration of anthracyclines in the adjuvant setting of early breast cancer, significantly correlated with patient outcome. It therefore seems that anthracycline-containing chemotherapeutic regimens can be considered optimal or suboptimal depending on whether or not they reflect the potential benefit offered by anthracycline administration.