Genetic Frontiers

05.15.134:45 AM ET

Angelina Jolie’s Double Mastectomy Was the Right Medical Choice

Treatments still lag far behind the crystal ball provided by genetic tests, but Angelina Jolie was right to take action after discovering she had the faulty BRCA gene. Dr. Kent Sepkowitz on medicine’s remarkable achievement.

Angelina Jolie made news Tuesday with her sober, nontheatrical, and informative revelation that she had undergone a bilateral mastectomy to prevent development of breast cancer.

However radical-seeming the intervention, the medical evidence for bilateral preventive mastectomy is extremely sound. According to the National Cancer Institute, the reduction in risk of breast cancer among women at medium and high risk for breast cancer is about 90 percent, though the procedure is not a guarantee that no breast cancer will occur. The recommendation is based on many studies reaching back to the 1990s that have shown the same remarkable protection in every report. In an early study from the Mayo Clinic, 639 women with a strong family history of breast cancer underwent the procedure and had a 90 percent reduction in breast cancer compared to the expected rate. When the blood test for the BRCA genetic mutation became available, the same research team analyzed the risk and found that the same risk reduction occurred in this genetically similar group.

As she disclosed, Jolie inherited a “faulty gene” from her late mother, the actress Marcheline Bertrand, that predisposed Jolie to both breast and ovarian cancer. BRCA mutations have been an area of tremendous research focus and interest in the last 20 years since Dr. Mary-Claire King, a mathematician and geneticist, first posited their association with breast and ovarian cancer. The mutation is generally thought to be called BRCA to signify the first letters of “breast” and “cancer,” but according to King, who did the naming, BRCA commemorates the great 19th-century French neurologist Pierre Paul Broca, who in addition to his contributions to our understanding of language also described the first “breast cancer families.” King was limited by convention to “just four letters,” and so BRCA became the term used.

The mutation occurs in about one in every 400 to 800 people and is passed on via old-fashioned Mendelian genetics as an autosomal dominant trait, meaning that half the offspring of an affected person will receive the trait. The role of the normal BRCA gene is straightforward: it is a “caretaker” responsible for repairing the routine, everyday genetic flaws created by the (very sloppy) ongoing assembly line of DNA replication. A person with a BRCA gene mutation, however, may be unable to make these daily repairs, leading to the accumulation of genetic defects and perhaps development of cancer.

X-ray technician Martina Rosenow, right, and assistant medical technician Marianne Warnholz, left, demonstrate the mammogram screening program in Berlin, Thursday, April 16, 2007.
X-ray technician Martina Rosenow, right, and assistant medical technician Marianne Warnholz, left, demonstrate the mammogram screening program in Berlin, Thursday, April 16, 2007. (Franka Bruns/AP)

The net result is staggering: the risk of developing breast or ovarian cancer by age 70 in a woman with a BRCA mutation approaches and even exceeds 50 percent. Because these mutations are relatively rare, their total contribution to overall breast cancer rates is only 5 percent to 10 percent—but for a person with the mutant gene, knowing about the risk is a very loud call to action.

The exact action, though, is not as straightforward as modern medicine would like. We have created a situation where gene-based medicine, that great 21st-century miracle, has given us the exact crystal ball we wanted it to provide. Yet the remedy is anything but modern—rather, it’s the somewhat brutal 19th-century approach: mastectomy. Granted, these are not the old days of the radical mastectomy, where not only the breast tissue but the chest wall muscles, or “pecs,” were removed. Still, for some, the prospect of mastectomy is not attractive, even when the consequences are dire. According to family legend, my mother, who died of breast cancer as a young woman, said to the surgeon as she was being wheeled to the operating room, “leave my breast alone—how would you like it if I cut off your balls?”

Thankfully, medicine has progressed sufficiently since my mother’s day that breast reconstruction has become routine, and many women now accept the surgery without such trepidation and even perhaps with some relief. Yet the BRCA and preventive mastectomy story is likely to be replayed in various forms in the years ahead as new gene mutations are associated with other cancers. Unfortunately, genetic insights are not the same as genetic treatments. Diagnosis and treatment always have lurched forward independently, each at its own erratic pace, and nowhere is this truer than in genetic medicine, where clinically relevant mutations are found daily but treatments lag far behind. It may be that for now, a meaningful test such as BRCA, an effective if dramatic intervention such as mastectomy, and a brave public face such as that provided by Angelina Jolie are the best 21st-century genetic medicine can provide. But for the many women whose lives may be saved by a combination of these three ingredients, this is a true modern miracle.