Operation of Major Breast Cancer Drug Explained


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Prof. Degani and Furman-Haran imaged tumor with MRI

One of the most puzzling aspects of the widely used breast cancer drug tamoxifen -- which shrinks estrogen-sensitive tumors yet is unable to kill cells from these tumors in tissue culture -- has been clarified by Weizmann Institute scientists working with doctors at the Sheba Medical Center near Tel Aviv.

The investigators found that tamoxifen destroys tumors by preventing them from maintaining their blood-capillary network. Without an adequately functioning life-support network, cancer cells die and the tumor regresses in size.

Participating in this study were group leader Prof. Hadassa Degani and graduate student Edna Furman-Haran of the Weizmann Institute's Department of Chemical Physics, Dr. Ada Horowitz and Iris Goldberg of the Department of Pathology of the Sheba Medical Center, and Dr. Antonio F. Maretzek, a visiting scientist from the University of Bremen.

Interest in tamoxifen stems from its wide use to prevent the recurrence of breast cancer in women who have undergone surgery to remove an estrogen-sensitive tumor. It is also being tested in patients in the United States and United Kingdom as an anticancer prophylactic in high-risk women.

Because only about half of breast tumors are estrogen dependent and potentially responsive to tamoxifen, the new Weizmann-Sheba study suggests seeking other drugs that destabilize the tumor capillary support system, and perhaps using them to control estrogen-independent breast tumors. Such new approaches could also complement tamoxifen therapy itself, as long-term treatment with the drug often leads to the appearance of estrogen-independent growths.

Using advanced magnetic resonance imaging (MRI) at high spatial resolution coupled with immunohistochemical techniques, Weizmann Institute and Sheba Medical Center researchers have studied how tamoxifen affects the growth of human breast carcinomas implanted in laboratory mice. They found that shortly after initiation of tamoxifen treatment, the tumors stopped growing and after two weeks, they showed an average 26% reduction in size and significant increase in the extent of necrosis. Specific histological staining of the endothelial cells comprising the microcapillaries showed a two-fold decrease in their density, indicating a reduced capacity of this tissue to deliver oxygen and vital nutrients.

This study was partially supported by the U.S.-Israel Binational Science Foundation and by the Israel Academy of Sciences and Humanities.