Biomolecular prognostic factors in breast cancer

To update clinicians on recent findings concerning the clinical usefulness of biomarkers in breast cancer, this review examines recently published papers dealing with promising prognostic/predictive biological factors. These factors can be classified according to their involvement in the main alterations characterizing tumor cells: self-sufficiency in growth signals, insensitivity to anti-growth signals, evasion of apoptosis, limitless replicative potential, sustained angiogenesis, and tissue invasion and metastasis.

Despite relevant research efforts and the identification of many putative good prognosticators, few of these factors are proving clinically useful for identifying patients at minimal risk of relapse, patients with a worse prognosis, or patients likely to benefit from specific treatments. Most of them, such as HER-2/neu, epidermal growth factor receptor, cyclin E, p53, bcl-2, vascular endothelial growth factor, urokinase-type plasminogen activator-1 and the recently discovered anti-apoptosis protein survivin, are suggested for possible inclusion in the category of biomarkers with a high level of clinico-laboratory effectiveness. However, no single biomarker was able to identify those patients with the best (or worst) prognosis or those which would be responsive to a given therapy. Novel findings derived from gene-expression analysis indicate that the simultaneous consideration of molecular alterations contributing to the hallmarks of cancer might provide clinically useful prognostic, and perhaps therapeutic, information.

Rapid translation of laboratory findings to clinical practice was hampered by many difficulties, including technical and statistical concerns, a lack of assay standardization and comparability, and the modest design of translational studies. Many studies are performed on too small series of patients to provide reliable results; the studies are often heterogeneous in terms of treatment, patients and tumor characteristics, and data may be evaluated using different analytical approaches and are thus not easily comparable. Adequately planned prospective studies are required to assess the clinical utility of biomarker determinations.