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15-YEAR ROAD TAKES DRUG TO MARKETPLACE UM researcher finds treatment for breast cancer


If patience is a virtue, Angela M. Brodie has waited long enough to be a saint.

After more than 15 years of painstaking work, the University of Maryland biochemist and pharmacologist has just seen her research move to the marketplace as a drug to treat breast cancer in post-menopausal women. The drug is aimed at stemming the course of the disease in women whose tumors have failed to shrink after conventional treatments.

Over the winter, Ciba-Geigy Corp. received approval to begin marketing the drug, called formestane, in Britain.

"I am really pleased to see something come from the science that is a direct help for patients with breast cancer," said Dr.

Brodie, a thin woman with long, wavy red hair, green eyes and an English accent.

The discovery of the drug also has helped point scientists and drug companies toward other drugs that help block the growth of breast cancer.

Her work began at the Worcester Foundation for Experimental Biology, where she went after a postdoctoral stint at the National Institutes of Health in Bethesda. Her research, which has always centered on reproductive health issues, particularly for women, began as an interest in the link between breast cancer and the hormone estrogen.

Previous research had shown that estrogen seemed to increase the growth of breast tumors in women. When some women with the cancer had their ovaries removed, the tumors diminished because the ovaries are a center of estrogen production, Dr. Brodie said.

So Dr. Brodie looked for compounds that would block the production of estrogen anywhere in the body, particularly in post-menopausal women, who appear to be more sensitive to estrogen.

The idea was to inhibit an estrogen-producing enzyme that is not only in the ovaries, but also in fatty tissues and other places in the body.

With her husband, Harry Brodie, a bio-organic chemist who was also working at the foundation, she experimented with various ,, compounds looking, in effect, for the key that fit the enzyme lock.

In 1979, she moved to the University of Maryland, where she continued the research; her husband moved to the NIH, where he is an administrator.

She tried several compounds in laboratory rats to determine whether the tumors would diminish. But the research was

momentarily stalled because there was no way to test the compound knownas 4 hydroxyandrostenedione, or 4-OHA, in women.

Dr. Brodie's luck changed at a Rome conference, where she met Dr. Charles Coombes of St. George's Hospital in England. He was persuaded by the lab data to set up a clinical trial at the hospital for patients whose treatment with radiation and other drugs had failed.

Those studies showed that the drug causes remission in about 30 percent of post-menopausal patients, a reasonable success given the fact that the women failed to respond to other types of treatment.

And once the results were published in the medical journal Lancet, several pharmaceutical companies showed interest.

The process probably wouldn't be as long today. Drug companies now aggressively pursue research in the laboratories, and universities have set up technology transfer departments to move research from the laboratory to the bedside.

"I think times have changed a lot," Dr. Brodie said.

The drug has been well received by British physicians who treat cancer patients, but Ciba-Geigy does not intend to pursue approval in the United States, a company spokesman said.

The company is trying to get Food and Drug Administration approval for another drug to treat breast cancer.

Dr. Brodie would not discuss financial details of the arrangement, nor would the university or the company.

Dr. Brodie has continued searching for new compounds to treat cancer, including drugs for prostate cancer. But she says women's health issues remain a crucial interest.

Today, those issues have begun to get more research money from the NIH and other federal agencies, and she called that a welcome change, saying, "I certainly think there are areas that need a lot of research."

In particular, she believes women being treated with estrogen after menopause should be closely followed by their physicians.

Such studies would tell doctors whether the estrogen might make women more susceptible to breast cancer or decrease their chances of having heart attacks and contracting other forms of cancer.

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