• Cell cycle analysis. Both normal and malignant cells go through a complete cell cycle known as mitosis . During one phase of the cycle (the S-phase), new DNA is synthesized in preparation for the division of one cell into two. Flow cytometry as well as other techniques are used to measure the S-phase fraction, or growth rate. The percentage of tumor cells in this S-phase is an indication of how rapidly a tumor is trying to grow. As might be expected, tumors with a high S-phase fraction (over 7 percent when measured by flow cytometry) in other words, growing rapidly—have a less favorable prognosis . The S-phase fraction for breast cancer can range from less than 1 percent to more than 20 percent of the cells. • Immunohistochemical detection of abnormal tumor proteins, including secreted enzymes and stress proteins, are under investigation. Lower levels of the enzyme cathepsin-D or specific "heat-shock" proteins, for example, are associated with better survival in some studies. There are also abnormal oncogene and growth factor-related products. The product of the HER-2/neu oncogene is overproduced in about one-third of breast cancers. The overproduction appears to be associated with earlier tumor relapses and lower survival rates. Another promising marker is the epidermal growth factor (EGF) receptor. • Several studies have shown that the number and density of tiny blood vessels in the tumor could be correlated with the risk of metastasis .