Prognostic and predictive factors revisited.

Standard prognostic factors include clinical and pathological staging, especially lymph node status and tumor size. Tumor grade and estimates of lymphatic invasion appear to be moderately strong predictive factors, but reproducibility is poor, especially for grade 2 tumors. Standard predictive factors include hormone receptor status and HER-2 amplification and/or over-expression for selection of endocrine therapy and, at least for clinical trials and in the metastatic setting, of trastuzumab, respectively. Three new markers appear particularly promising: detection of bone marrow metastases, either at baseline or after 2-4 years of follow-up; expression of UPA/PAI-1 by the primary cancer; and recognition of simultaneous multiple gene expression patterns, or "signatures." Important caveats exist for each of these. Although new technologies offer exciting and promising new approaches to determining a patient's prognosis and whether she will or will not benefit from specific therapies, few have been validated in well-designed, Level of Evidence I studies. In particular, available data are often confounded by patient selection and the effects of systemic therapy, which are often not determined prospectively, not included in analyses, and not reported adequately.