The Breast Cancer Gene: a Woman's Dilemma

By Larry Thompson/Washington

Cancer stalks the women in Anna Fisher's family. Her grandmother died of "female cancer" -- probably ovarian -- in the 1940s. When Fisher was five, her mother developed breast cancer. After having a mastectomy, the mother survived for a decade, only to die from cancer originating in the other breast. Fisher also has a maternal aunt who had ovarian tumors, and five cousins contracted breast cancer. Malignancy is simply part of her pedigree.

So it was no big surprise, though still a shock, when in 1990 doctors found she had ovarian cancer. Thanks to aggressive surgery and intensive chemotherapy, Fisher, a 41-year-old dietitian living in Pittsburg, California, made a remarkable recovery and became tumor-free. But she knew her future was still menacing. Scientists had recognized for several years that ovarian and breast cancer sometimes ran together in families, as if linked in some way. Fisher's oncologist proposed a once unthinkable step: a "prophylactic" double mastectomy. Removing her breasts, the doctor said, could save her life.

At first Fisher would not even consider it. "I always lived in fear of getting breast cancer because most of the women in my family got it," she said. "But I was too busy trying to survive ovarian cancer to think about breast cancer." Too busy until she read about the work of Mary-Claire King, the University of California, Berkeley, geneticist who is searching for the gene that causes the inherited form of breast cancer and also increases the risk of ovarian cancer.

In a stunning announcement three years ago, King unveiled evidence that such a rogue gene exists. By analyzing chromosomes from women in families repeatedly hit by cancer, the scientist discovered that the victims shared on chromosome 17 a pattern of genetic markers -- stretches of identical DNA -- not found in those free of the disease. This did not mean that the markers caused cancer but that the gene responsible lurked somewhere nearby on the same chromosome.

After joining King's study group, Fisher learned that she carried the telltale pattern of markers. The agonizing question: What should she do? Huge numbers of women will eventually face the same dilemma. The inherited form of breast cancer accounts for 5% to 10% of cases, says King, meaning that "there might be half a million women who either already have or will develop the disease because of this gene." Carriers have an 85% chance of getting breast cancer by age 65.

King's research set off a race among many laboratories to pinpoint the location of the gene. Having joined forces with famed gene hunter Dr. Francis Collins, King hopes to track down the culprit within the next few months. That would lead to a simple blood test for the presence of the gene.

But not to simple answers about what to do. Should women with the gene have mastectomies quickly or should they have frequent mammograms to detect cancer early? Neither choice is foolproof, and no studies of survival rates have been completed. "The literature is full of anecdotal reports of women who had breast cancer even after prophylactic surgery," says King. "If a woman has a mastectomy, she is doing it based on common sense and logic, not on statistical proof."

Fisher's common sense told her that her breasts posed too great a risk, and she had them removed the week before Thanksgiving. "I did the best that I could to prevent breast cancer," she says. "I hope it will be enough."