Knowledge That Can Save You

It was a destiny Melodee stokes desperately wanted to avoid. The youngest of five girls, Melodee watched her oldest sister, Brenda, now 60, battle breast cancer twice. Last year another sister, Cindy, died of the disease at the age of 47. "She was a beautiful, vibrant woman, and when she died she was a very frail, sick person," says Melodee. "I didn't want to put my family through that." In April 2005, Melodee had a blood test to see if she, like her two sisters, carried a mutation in the breast-cancer gene, BRCA2, which increases the odds of both breast and ovarian cancer. She did. Two months later, Melodee had both her breasts removed; this past summer, she had a hysterectomy. "I'm going to do something that will make sure I'm never sick like Aunt Cindy," she explained to her daughters Heather, 11, and Danielle, 8. The girls responded, says Melodee, now 40, with "the biggest smiles."

It was 10 years ago this month that tests for mutations in two breast-cancer genes, BRCA1 and BRCA2, hit the market. Early on, many doctors worried that the tests would do more harm than good--patients might lose their insurance, maybe even their jobs, if the results came back positive. And they'd be emotionally devastated by the news. "There was a real concern that people might commit suicide," says Dr. Kenneth Offit, of New York's Memorial Sloan-Kettering Cancer Center. Today, those fears have been largely diminished, but new, wrenching and ethically complicated questions have emerged: Should healthy women undergo radical surgery? What do parents tell their children if they test positive? What if one family member wants to know and another doesn't? Women like Melodee, says Dr. James Evans, of the University of North Carolina at Chapel Hill, "are unwitting pioneers in a whole new era of medicine."

Genetic testing makes the most sense when, as in the case of breast cancer, mutations have a major impact on health and when steps can be taken to intervene. BRCA1 and 2 alterations (which account for 5 to 10 percent of breast cancers) don't guarantee that the disease will strike. But they do increase a woman's risk dramatically: from about 7 percent in the general population to as high as 87 percent in those who test positive. Now doctors can help patients manage their risk more aggressively than ever, says Sloan-Kettering's Offit, through frequent screenings, including MRI exams and preventive or "risk-reducing" surgeries. "Today, there's information and we understand what to do with it," says Dr. Louise Morrell of Boca Raton (Fla.) Community Hospital.

Genetic testing is still in its infancy, but as awareness grows, more people are opting in. Myriad Genetics, which owns the BRCA1 and 2 tests, has tested 100,000 patients and now screens more than 200 a day. They include Rivka From and her daughters, Courtney, 26, and Carlye, 22. Rivka's mother died of ovarian cancer at 40; two years ago, Rivka was diagnosed with breast cancer. Since then, she and her daughters, who now have routine screenings, have all tested positive for BRCA1 mutations. The knowledge has affected each one differently. Rivka was relieved to know the truth and had a double mastectomy. Courtney, who'll be married in February, was propelled into action. She plans to have two kids by her mid-30s. After that, she'll likely have her breasts removed. Carlye, a college junior, has mixed feelings. "It's very scary," she says. Among her concerns: When should she reveal her status to a potential boyfriend? And will he flee once he knows? At the same time, she feels fortunate to take control of her health. "I look at this test," she says, "as saving my life one day."

The decision to undergo prophylactic double mastectomy is exceedingly personal. The majority of women who have a mutation but are still healthy opt against it. Deborah Posner, 39, wouldn't even talk about it after she tested positive. "It was unbearable," she says. But a mammogram scare last spring made her reconsider and she had surgery in June. The procedure cuts the risk of breast cancer by at least 90 percent, but it's not foolproof. And major surgery carries risks. "There are physicians and women who believe this is too aggressive," says Marc Schwartz of Georgetown's Lombardi Comprehensive Cancer Center.

A double mastectomy is not the only surgical option. More women with BRCA1 or 2 choose to have their ovaries removed instead, especially after having kids. Some, like Posner, opt for both. An oophorectomy can be done laparoscopically and has a double benefit in premenopausal women: reducing the risk of ovarian cancer (which is much harder to screen than breast cancer) by at least 90 percent, and cutting the breast-cancer risk by half. The key for patients, says Schwartz, is in-depth genetic counseling so women can make informed decisions for themselves.

As genetic testing advances, questions are arising over how far the field should go. Should screening start before birth? Already, several clinics are using a technique called pre-implantation genetic diagnosis (PGD) to screen embryos created by couples who've tested positive for BRCA mutations. Only embryos without alterations are then selected for implantation. Dr. Mark Hughes, of Genesis Genetics Institute in Detroit, says PGD has resulted in 19 healthy babies at his clinic so far. The approach is controversial, especially for a disease that may or may not strike in adulthood. But Hughes says families have the right to seek help. "We want to prune this from our family tree forever," patients tell him. "We've seen enough."

Melodee Stokes has, too. "Why not use medical technology to make yourself healthier?" she asks. A question that will continue to loom large in the years ahead.