Laboratory Results Suggest Tamoxifen May Inhibit Angiogenesis

NEW ORLEANS—A laboratory study suggests that tamoxifen (Nolvadex) could inhibit angiogenesis at higher dose levels than currently used for adjuvant therapy of breast cancer.

Tamoxifen, which blocks the estrogen receptors on breast cancer cells, has been most efficacious in breast cancer patients whose tumors are estrogen-receptor positive. However, it has also been beneficial to a minority of patients whose tumors are estrogen-receptor negative. This led investigators at Louisiana State University Medical Center to speculate that the agent might have an antitumor effect other than its known hormonal effect.

The researchers developed a model of angiogenesis using human placental veins, said Michael O. Meyers, MD, who presented the study at the 88th Annual Meeting of the American Association for Cancer Research (AACR).

The placental vein disks were cultured in a 0.3% fibrin clot overlaid with media containing fetal bovine serum (FBS), and then exposed to tamoxifen at various concentrations. The incidence of angiogen-esis was evaluated six, nine and 12 days later, and compared with control disks containing just FBS.

At the highest tamoxifen concentration (10–4 molar), the agent significantly inhibited the initiation of angiogenesis in the model at all three evaluation periods. This level, Dr. Meyers noted, is much higher than the typical plasma drug concentration achieved with the standard adjuvant tamoxifen dose for breast cancer of 20 mg/day.

“Our study findings suggest that tamoxifen at high doses is an inhibitor of angiogenesis,” Dr. Meyers commented. “By administering tamoxifen at higher doses than those currently used in the treatment of breast cancer, we may be able to produce better response rates in patients.”

The investigator plan to conduct animal studies to explore tamoxifen’s antian-giogenesis effects further, and eventually hope to study this approach in clinical trials.