Ricka Neuman says she hit the medical jackpot four years ago when, hoping to prevent the recurrence of her breast cancer, she enrolled in a clinical study to test a drug designed to block the production of estrogen, a hormone that can stimulate certain tumors.
The drug Neuman took inhibits an enzyme known as aromatase. Pioneered by Angela H. Brodie, professor of pharmacology and experimental therapeutics at the University of Maryland's Greenebaum Cancer Center, it has been shown to shrink tumors and significantly reduce the risk of breast cancer recurrence.
"I won the lottery -- but not the one you're thinking of," Neuman told her doctors. "I won the clinical study lottery."
She has continued to take the drug daily and has remained cancer free. Recently Neuman, who sits on the center's board with Brodie, had the opportunity to personally thank the scientist for "this amazing thing she's done for women, to help them feel as though they're in control and that they can do something to try to decrease their risk of recurrence."
In the United States alone, it is estimated that more than 211,000 women will be diagnosed with breast cancer in 2005, and many of them stand to benefit from Brodie's aromatase inhibitor.
Given the magnitude of her contribution, Brodie, 70, shouldn't have been surprised when she learned in May that she had been selected by an international panel of scientists to receive the Charles F. Kettering Prize for the most outstanding recent contribution to the diagnosis or treatment of cancer.
Brodie, who is the first woman to win the award, said she was shocked. She received a medal and $250,000. Brodie is "one of the most humble and unassuming individuals you would ever want to meet," said Kevin J. Cullen, director of Greenebaum Cancer Center.
The award is as much a testament to her determination and perseverance as it is to her scientific acumen. When the Manchester, England-born scientist first suggested in the early 1970s that there might be a drug that could limit the production of estrogen, she was met with skepticism throughout her field. At the time, cancer researchers were focused on a newly developed drug called tamoxifen, which prevents estrogen from binding to cancer cell receptors.
But tamoxifen itself is a weak estrogen, and Brodie questioned how well it could block tumors. Patients on tamoxifen also ran a higher risk of endometrial cancer and strokes. Brodie wanted to find a way to limit the production of estrogen, instead of blocking its effects. Leading medical journals were dubious -- editors at the medical journal Cancer Research rejected Brodie's first paper on the topic, saying the theory was "too obvious," Brodie recalls.
At the time, the only way to limit estrogen production was to remove a woman's ovaries, adrenal and pituitary glands. For a less invasive alternative, Brodie reasoned that there had to be a way to shut off the production of aromatase, an enzyme critical to making estrogen. She and her colleagues at the University of Maryland concocted roughly 200 compounds until they found one that effectively stymied the aromatase.
Her lab results looked good, but as Brodie said, "The clinical people and the pharmaceutical people, they weren't so interested in the animal data." She needed proof that the drug would work on humans.
In 1982, while Brodie was teaching and continuing research at the University of Maryland, researchers in London conducted a clinical trial using Brodie's initial aromatase inhibitor. The results were positive: Out of 11 patients, four responded quickly to the drug. After roughly three months, their tumors shrank to less than 50 percent of their original size.
Brodie got back on the phone with the pharmaceutical companies.
Brodie's feats -- inventing the drug, testing it and manufacturing a kilo of it for the 1982 trial -- were "an extraordinary amount of work for an individual investigator to do," Cullen said. "Most people would have found it too daunting to be realistic, but she was willing to put in superhuman effort to get it done. Now women from all over the world benefit from it."
Formestane, the initial aromatase inhibitor, was released for worldwide use in 1994. The latest version, letrozole, was proven to be so effective that clinical trials were stopped early so that patients who were taking a placebo could instead be given letrozole. The drugs are most effective in post-menopausal women with breast cancer, the population most susceptible to the disease and whose tumors are most affected by estrogen levels.
Brodie's aromatase inhibitors are "a major advance," said Samuel A. Wells Jr., president of the General Motors Cancer Research Foundation, which sponsors the award. "I'd say we're just at the start of understanding how useful these compounds are."
Brodie said she will continue to experiment with aromatase inhibitors and will study hormone therapy for prostate cancer as well.
She has interests outside of science: She's an avid rock climber and horseback rider, and two years ago she went sky diving -- activities that suggest that, despite her soft British accent and gentle demeanor, she's a thrill-seeker.
That's partly what keeps her tethered to cancer research -- the adrenaline that comes with discovering new ways to combat tumors and help save the lives of thousands of women.
"It's wonderful," Brodie said. "And yes, it's exciting, too."