Conventional and new emerging prognostic factors in breast cancer: an update

This article reviews the conventional clinicopathological, as well as the principal new emerging prognostic factors of breast cancer and proposes a tumor marker utility grading system for their use. In spite of the many advances in molecular biology toward better defining the biological aggressiveness of the primary malignancy, the conventional node-negative status, tumor size and grade are still the strongest predictors of relapse-free survival and/or overall survival. Microvessel count and bone-marrow micrometastases, among the more recently studied clinicopathological prognostic factors, and amplification and/or p53 mutation and S-phase fraction among the biological ones must be considered investigational, although, with enough documentation recommending their usefulness. Estrogen and/or progesterone expression, c-erbB-2 amplification and/or mutation are the prognostic factors currently included in the principal clinical guidelines. They also enable probable forecast of the response to endocrine treatment or chemotherapy. In particular, c-erbB-2 is used to define the different risk categories of node-negative operated breast cancer patients. In recent years, microarray and quantitative reverse-transcription PCR technologies have enabled the study of multiple genetic alterations and computer algorithms have been developed for visual recognition of tumors that share so-called 'signatures'. So far, different gene-expression patterns with different prognoses have been identified but methodological problems remain to be solved prior to routine use.