One of the defining moments in the history of breast cancer occurred in 1974 when first lady Betty Ford spoke openly about her mastectomy, lifting a veil of secrecy from the disease and ushering in a new era of breast cancer awareness.
Now, four decades later, another leading lady – actress Angelina Jolie – has focused public attention on breast cancer again, this time with an even bolder message: A woman at genetic risk should feel empowered to remove both breasts as a way to prevent the disease.
Jolie revealed Tuesday that, because she carries a cancer-causing mutation, she has had a double mastectomy.
"She's the biggest name of all, and I think given her prominence and her visibility not only as a famous person but also a beautiful actress, it's going to carry a lot of weight for women," said Barron H. Lerner, a medical historian and the author of "The Breast Cancer Wars."
Breast cancer experts and advocates applauded the way Jolie explored her options and made informed decisions, saying it might influence some women with strong family histories of breast cancer to get genetic tests.
Some doctors also expressed worry, however, that her disclosure could be misinterpreted by other women, fueling the trend toward mastectomies that are not medically necessary for many early-stage breast cancers.
In recent years, doctors have reported a virtual epidemic of preventive mastectomies among women who have cancer in one breast and decide to remove the healthy one as well, even though they do not have genetic mutations that increase their risk and their odds of a second breast cancer are very low.
Jolie wrote on the op-ed page of the New York Times that she had tested positive for a genetic mutation known as BRCA1, which left her with an exceedingly high risk for developing breast and ovarian cancer. Her mother died at 56 after nearly a decade with cancer, though Jolie did not specify which type. Media reports said it was ovarian cancer.
After genetic counseling, Jolie opted to have both breasts removed and to undergo reconstructive surgery.
Jolie, who declined to be interviewed for this article, was treated at the Pink Lotus Breast Center in Beverly Hills, a clinic opened in 2009 by Dr. Kristi Funk, who is identified on the website as a former director of patient education at the breast center at Cedars-Sinai in Los Angeles.
Her condition is not common. Mutations in BRCA1 and another gene called BRCA2 are estimated to cause only 5 percent to 10 percent of breast cancers and 10 percent to 15 percent of ovarian cancers among white women in the United States. The mutations are found in other racial and ethnic groups as well, but it is not known how common they are in those groups.
About 30 percent of women who are found to have BRCA mutations choose preventive mastectomies, said Dr. Kenneth Offit, chief of clinical genetics at Memorial Sloan-Kettering Cancer Center in New York. Those who have seen family members die young from the disease are most likely to opt for the surgery.
"It's important to make it clear that a BRCA mutation is a special, high-risk situation," said Dr. Monica Morrow, chief of the breast surgical service at Memorial Sloan Kettering. For women at very high risk, preventive mastectomy makes sense, but few women fall into that category, she said.
Jolie's decision highlights the painful dilemma facing women with BRCA mutations.
"She is a special case, and you can completely understand why she did it," said Dr. Susan Love, the author of a best-seller, "Dr. Susan Love's Breast Book," and a breast surgeon. "But what I hope that people realize is that we really don't have good prevention for breast cancer. When you have to cut off normal body parts to prevent a disease, that's really pretty barbaric when you think about it."
Women who carry BRCA mutations have, on average, about a 65 percent risk of eventually developing breast cancer, as opposed to a risk of about 12 percent for most women. For some mutation carriers, the risk may be higher; Jolie wrote that the estimate for her was 87 percent.
Because the BRCA mutations are rare and the test expensive – about $3,000 – it is not recommended for most women. But for women with breast cancer who do have mutations, knowing their status can help them make treatment decisions, such as whether to have an unaffected breast or their ovaries removed.
Women who should consider testing are those who have breast cancer before age 50; a family history of both breast and ovarian cancer; or many close relatives with breast cancer, especially if it developed before age 50. Any woman with ovarian cancer should consider being tested, as should Ashkenazi Jewish women with breast or ovarian cancer.
Men with breast cancer and their families should also inquire about the possibility of a genetic predisposition to the disease.
Because the cancer risks for carriers are so high, women with the mutations are often advised to have their breasts and ovaries removed as a preventive measure.
There is no reliable way to screen for ovarian cancer, and most cases are detected at a relatively late stage, when the disease is harder to treat and more likely to be fatal.
Jolie, 37, said that she had a 50 percent risk of ovarian cancer.
"I started with the breasts, as my risk of breast cancer is higher than my risk of ovarian cancer, and the surgery is more complex," she wrote.
Removing the breasts is not the only option, said Dr. Susan M. Domchek, an expert on cancer genetics at the University of Pennsylvania. Some women with BRCA mutations choose close monitoring with mammograms and MRI scans once a year, staggered so that they have one scan or the other every six months. Those tests offer a chance to find cancer early.
Jolie's celebrity and her roles as a mother of six and a movie star who plays strong women may give her decision far-reaching impact.
Dr. Isabelle Bedrosian, a surgical oncologist at M.D. Anderson Cancer Center in Houston, has been a vocal critic of the trend toward double mastectomy among women who are not at high genetic risk. However, she hopes the decision by Jolie will focus women on the value of genetic counseling and making informed decisions.