Alterations in protooncogenes and tumor-suppressor genes at the DNA and/or protein level indicate the biological properties of individual breast cancers. Information on these genetic and protein alterations is considered to be useful diagnostically and these alterations are now being applied in routine diagnosis or are under investigation for diagnostic application in the areas of: 1) determination of indications for specific therapies for advanced or metastatic breast cancers; 2) prediction of the response of primary tumors to adjuvant or neoadjuvant systemic therapies; and 3) identification of patient groups at high or low risk of recurrence from node-negative breast cancer.