Living with Lethal Genes: Some Advice

By S.C. GWYNNE

Kristen, which is not her real name, is visibly distraught. She sits meekly and unhappily before her doctor and her genetic counselor, as though a world of trouble had just descended upon her frail shoulders. And in fact it has. A Duke-administered genetic test has revealed she has an extremely high risk of having a recurrence of the breast cancer she had three years before. The test has shown that a gene mutation is likely to run in her family. Kristen, who is in her 40s, is here to talk about what that means and what she must do about it. She has insisted upon anonymity because of the shattering implications of this news--for herself and many others.

"I'm feeling a lot of anxiety," she says glumly. "I'm not really sure I want to hear those numbers yet." Although she is deeply disturbed by the test results, her case nonetheless shows how Duke is able to move its cutting-edge research quickly into the realm of patient care. Kristen's gene mutation was diagnosed in a Duke laboratory run by Andrew Futreal, a researcher who had a hand in the discovery of one breast cancer-susceptibility gene--known as BRCA1--and who co-discovered a second, BRCA2. Her doctor is Dirk Iglehart, a surgeon who also runs a large tumor biology laboratory. The genetic counselor, Shelly Clark, advises patients on the far-reaching effects of such lethal genes.

Just how far-reaching is distressingly apparent in the ensuing conversation. Women with this gene mutation have an 85% lifetime risk of breast cancer and a 50% risk of ovarian cancer. Kristen faces as much as a 60% chance of cancer in her other breast. She must decide whether to have her breasts removed, or to pursue various other pre-emptive treatments. But that is just the beginning. Once a patient knows about her genetic predisposition to cancer, she must decide whether or not she is going to lie on the myriad forms and applications that ask her to divulge such conditions: life- and medical-insurance policies, job applications and so on.

Then there are the implications for Kristen's family. Because this is a familial gene, there is a good chance that her 20-year-old niece has the same problem. By telling her this news, Kristen will effectively shatter her world too. If the niece also tests positive, to whom should she divulge this? Her boyfriend; her fiance? Should the young woman have a mastectomy? Should she have children, when the chances of her daughters' having it are 50%? The niece too will be tempted to lie on official forms. Clark, Iglehart, Kristen and her husband talk about all this.

"How do you feel about the option of prophylactic mastectomy?" asks Clark. "I get the sense you're not quite ready to jump on the bandwagon."

"Not yet," says Kristen. "We're going to go home and think about this."

Iglehart reminds her gently that "the good news is that the survival rate with breast cancer exceeds 85%." Still, Kristen must decide: have both breasts removed; take the drug Tamoxifen, whose possible side effects include blood clots and endometrial cancer. Or, more frightening still: do nothing.

--By S.C. Gwynne