EVALUATING THE POTENTIAL USEFULNESS OF NEW PROGNOSTIC AND PREDICTIVE INDICATORS IN NODE-NEGATIVE BREAST-CANCER PATIENTS

The incidence of breast cancer is increasing in all Western countries. Due both to a more widespread public education and to early diagnosis by mammography screening programs, the percentage of patients with no de-negative breast cancer has gone up to 70%. Thus, node-negative brea st cancer is a major public health problem and, consequently, clinical research in this setting is an expanding field. A recent overview ana lysis confirmed the results of rive prospective randomized clinical tr ials suggesting that systemic adjuvant therapy can benefit node-negati ve breast cancer patients. Because of the heterogeneity of node-negati ve breast cancer, it is reasonable to attempt to avoid excessive treat ment morbidity and costs by using selective prognostic markers to iden tify patients at high risk for disease recurrence who are eligible for postsurgical systemic adjuvant therapy. It is also desirable to use p redictive markers in selecting the therapy to which each patient is mo re likely to respond. The need for additional prognostic and predictiv e factors has led to identification of a plethora of potentially usefu l markers. As a result, the selection of patients at different risks o f developing node-negative breast cancer and the choice for appropriat e therapy remain difficult and confusing for the clinician. Moreover, the majority of studies have examined new markers individually rather than by multivariate analysis and retrospectively rather than prospect ively. Thus, there are also important methodologic biases in such stud ies. This analysis consists of (a) defining the clinical ''problem,'' (b) defining the terms of prognostic and predictive factors, (c) sugge sting more appropriate laboratory and clinical approaches to properly evaluate a new indicator, (d) identifying the subsets of patients in w hom the use of new prognosticators is warranted and of particular impo rtance, and (e) providing some direction for future research on this t opic. Our ultimate goals are to facilitate the understanding of node-n egative breast cancer prognostic markers among clinicians. to help the m select the most appropriate indicator for specific situations, and t o recommend methodology for future research.