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Cancer researcher honored

THE BALTIMORE SUN

The good-news phone call came on her birthday.

It was Sept. 28, 1982. At the time, cancer researcher Angela Brodie had already spent years battling scientific skepticism that she had found a better way to treat breast cancer. Her lab studies suggested she had synthesized a drug that could limit the production of estrogen, the hormone that usually makes breast cancer tumors grow in older women.

But she needed human proof. While teaching at the University of Maryland School of Medicine, Brodie searched for an opportunity for a clinical trial and found one in England.

She remembers the excitement she felt when she learned from her British collaborator that the drug she had prepared and shipped from her lab in Baltimore had arrested tumors in a British woman whose cancer was resistant to the standard therapy.

"I remember seeing the first patients," she recalls. "They were middle-aged ladies - and they were doing fine. I was even more ecstatic than they were."

Recently the 70-year-old researcher received another golden phone call: She was chosen by an international panel of scientists, including Nobel laureates, to receive the Charles F. Kettering Prize, an honor that recognizes "the most outstanding recent contribution to the diagnosis or treatment of cancer."

Along with the medal and $250,000 award she will receive next month, Brodie has also earned the distinction of becoming the first woman to receive this prize.

"Dr. Brodie played a pivotal role in the development of a group of compounds referred to as aromatase inhibitors," says Sam Wells, president of the General Motors Cancer Research Foundation, which sponsors the award, one of three prizes it has presented annually since 1979.

"These agents are particularly effective in the treatment of post-menopausal women with metastatic carcinoma of the breast," Wells adds, "and appear to be more effective than estrogen-blocking agents such as tamoxifen."

Last year, in fact, several studies - one an international study of 9,000 older women with localized breast cancer - demonstrated that aromatase inhibitors are not only more effective than tamoxifen at preventing a recurrence of breast cancer but also freer of side effects. These FDA-approved drugs, known generically as anastrozole, exemstane and letrozole, are now used worldwide.

Determined researcher

"What Angela has done is arguably one of the most important advances in the treatment of breast cancer in the last decades," says Kevin Cullen, director of the University of Maryland Greenebaum Cancer Center. "She's also one of the world's most humble and unassuming researchers."

Since 1979, when Brodie began teaching at the University of Maryland medical school, she has raised a family, taught hundreds of students and mentored post-doctoral fellows while pushing for ways to get aromatase inhibitors to women suffering from breast cancer.

"It was a little bit of an uphill battle," she says in a soft voice laced with a British accent. "Getting it from the lab to the clinic was definitely tough. But I was always sure we were right - that things were improving, step by step; that this didn't have to be the cure for cancer as long as it would provide some benefits to patients.

"Now that we've finally proved it to be very valuable," she adds, "it's wonderful to know it's helping the lives of so many women."

Brodie grew up near Manchester, England, in a family familiar with scientific innovation. Her late father, organic chemist Herbert Hartley, helped develop the industry for polyurethanes, plastic used in liquid coatings and paints. But he got an award from Prime Minister Winston Churchill for designing the antitank hand grenade used in World War II.

She says he inspired her love of science and life outdoors: As a child, she became an accomplished rock climber and accompanied her father on mountaineering trips in England and Europe. A petite, slender woman with wavy strawberry blond hair, Brodie still enjoys running and riding her Morgan horse on trails near her Howard County home.

When she was 10, Brodie began studying at a Quaker boarding school where she was "inspired to be of use to the community." She also discovered the work of British scientist Kathleen Lonsdale, a pioneer in the use of X-ray crystallography.

In 1961, after Brodie received her doctorate in biochemistry, she came to the United States on a fellowship from the National Institutes of Health, which has supported her research ever since. She met and married Harry Brodie, a chemist from New York, and plunged into what would become her life's work at the then-Worcester (Mass.) Foundation for Experimental Biology.

When the Brodies' two sons were born, she worked part-time for a while, helping her husband with his studies of estrogen biosynthesis.

It was an exciting time: President Nixon had declared war on cancer, and female scientists were feeling the stirrings of feminism - especially at the Worcester Foundation, where the birth control pill was developed.

Brodie says she became interested in trying to improve treatment for breast cancer when she worked as a graduate student in a cancer hospital in Britain. The standard care at that time - such as the removal of ovaries and adrenal and pituitary glands - convinced her of the urgency of finding a better approach.

In the 1970s, medical researchers came up with one answer: tamoxifen. The drug, which prevents estrogen from binding to cancer cell receptors, is effective against the form of breast cancer that uses estrogen to grow.

Because tamoxifen also serves as a weak estrogen, however, Brodie realized that it might not block tumors sufficiently. Other researchers were concerned that it might also put patients at increased risk for endometrial cancer and stroke.

Rather than searching for a drug that would block estrogens, Brodie looked for a way to limit its production. Aromatase inhibitors, she discovered, undercut the body's ability to even create the hormone. Her husband synthesized the early inhibitors that became the basis for the compounds she used. Later, when he moved on to an administrative post at the National Institutes of Health, Brodie continued her research at the University of Maryland.

Many to benefit

The drug therapy she pioneered has proven to be most effective in post-menopausal women with breast cancer. Not only does that group represent the largest number of women with the disease but also the greatest number whose cancer is estrogen-sensitive and most likely to benefit from this treatment.

Some believe that aromatase inhibitors should be the first choice in treating as many as half of the 211,000 U.S. women who develop breast cancer every year.

When Brodie was at Worcester, she sometimes compared notes with fellow Brit Craig Jordan, a scientist who had grown up five miles away from her own home, but whom she met only after they both had moved to the United States. Two years ago, Jordan won the Kettering Prize for his contributions to combating breast cancer with tamoxifen.

Both scientists also have won the Brinker Award for their research from the Susan G. Komen Breast Cancer Foundation.

Jordan, who is sometimes called "the father of tamoxifen," has called Brodie "the mother of aromatase inhibitors."

"Her pioneering medicine ignited the interest of the pharmaceutical industry to make much better drugs today," he says. "She led the way to say there is a better way than tamoxifen."

"Research is a relay race," Jordan adds. "You keep passing the baton."

Angela Brodie shows no signs of slowing down. She is still teaching pharmacology and experimental therapeutics and supervising the lab work of a dozen post-doctoral fellows and graduate students while plowing through a stack of grant applications.

Extending the work she began more than a decade ago, she's looking at newer generations of drugs used not only for breast cancer but for prostate cancer as well.

"I've learned it's important to work hard and to stick to a project," she says. "To just stay with something when you think it's worthwhile."

Dr. Angela Brodie

Born: Sept. 28, 1934, near Manchester, England.

Education: Ph.D. in biochemistry.

Home: Fulton, Md.

Employment: Professor of pharmacology and experimental therapeutics at the University of Maryland School of Medicine and a researcher at the University of Maryland Greenebaum Cancer Center. Has published more than 200 scientific papers and serves as an editor for four journals, including Cancer Research.

Latest award: Charles F. Kettering Prize for her pioneering work at developing aromatase inhibitors, a new class of drugs that help prevent a recurrence of breast cancer in post-menopausal women by limiting the amount of estrogen their bodies produce.

Family: Married to retired chemist Harry Brodie. They have two sons - a physicist and a teacher - and two grandchildren.

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