Angiogenesis and breast cancer.

Antiangiogenesis is an appealing therapeutic modality for the treatment of a number of clinically important diseases, including human malignancies and specifically breast cancer. For years, such an approach has remained little more than good theory. However, recent studies have suggested that specific antiangiogenic agents might be effective and safe, and preliminary clinical trials are now being planned to test these drugs. Although early studies will be designed to test the safety of these agents, it seems most likely that they will have their greatest efficacy early in the course of the disease, for example, in the adjuvant setting. Moreover, they will almost certainly be most active when used in combination, both with other antiangiogenic agents and with other modalities such as classic chemotherapy or endocrine therapies or both. Given the potential for monitoring tissue neovascularization and circulating angiogenic factors, one might also speculate that therapies might be chosen based on specific, individual characteristics, not unlike the current use of tumor steroid hormone receptor content to determine the appropriate use of endocrine therapy. In fact, individual responses to antiangiogenic molecules may be important. For example, one group of investigators investigated antiangiogenic activity of a large, polyglycosylated lipid, maltose tetrapalmitate (MTP). They found that the genetic ability of inbred mice to respond to MTP is specifically related to the antiangiogenic and antitumor effects of MTP. Mice genetically unable to respond to MTP were not protected from tumor-graft growth by MTP, whereas responders survived for long periods of time. Although the clinical field of antiangiogenic therapy remains in its infancy, physicians in the future may be as concerned about the "angiogenic profile" of individual patients as they are today about clinical staging and ER status.