New data on chemotherapy in the adjuvant setting

In the last few months, there have been three sets of new, provocative data that might have important implications for the daily prescription of adjuvant chemotherapy (CT) in the future. (1) Urokinase-type plasminogen activator (UPA) and type 1 plasminogen activator inhibitor (PAI-1), two molecular markers of invasion already known for their powerful prognostic value in node-negative breast cancer, seem to predict for enhanced benefit from adjuvant CT, while the benefit from adjuvant endocrine therapy seems independent of them. The predictive value of these markers, however, remains suboptimal and an important limitation lies in their evaluation through a cytosolic assay, which is compromised for small tumours (< 1 cm). (2) Breast cancer 'gene expression profiles' have been identified through DNA-microarray technology and seem to be better predictors of clinical outcome in young women (less than 55 years old) with stage I or II breast cancer, when compared to the currently used clinical-pathological criteria. Remarkably, these molecular data suggest that the prognostic profile of breast cancer does not depend on lymph node status and that it is possible to identify a group of node-positive breast cancer patients with an unexpectedly good prognosis. Prospective and independent confirmation is needed, but these data are fascinating and carry the hope that CT decision-making in breast cancer will be greatly facilitated in the future. (3) The recently reported CALGB 9741 (or INT 69741) trial shakes our belief that 'one cycle of CT every 3 weeks' is the adequate adjuvant treatment for node-positive breast cancer. Launched in 1999, it aimed to test two novel concepts based on mathematical models of tumour cell growth kinetics. Concept 1 implies that dose-densification of CT, i.e., delivering drugs at reduced intervals, will maximize the chances of eradicating the tumour; and concept 2 extends the first one to encompass situations of heterogeneous drug sensitivity through the use of sequential dose-dense, non-cross-resistant single agents or regimens. The 3-year results of this trial strongly support concept 1; a longer follow-up and a confirmation study are desirable before recommending changes in routine patient care. (C) 2003 Elsevier Ltd. All rights reserved.