Angelina Jolie's Mastectomy: BRCA Testing in the Spotlight

Kate Johnson

May 16, 2013 Superstar Angelina Jolie's headline revelation this week about her positive genetic test for the BRCA1 mutation and subsequent double prophylactic mastectomy has stunned the world and put the entire field of breast cancer medicine on high alert.
Her story is "the epitome" of individualized medicine, said Eric Topol, MD, editor-in-chief of Medscape.
"She took charge by getting the test done, getting the critical information about whether she would be at risk for breast cancer and how high that risk would be, and then making a key decision of preventive surgery," said Dr. Topol, who is director, Scripps Translational Science Institute Chief Academic Officer, Scripps Health Professor of Genomics, the Scripps Research Institute.
With more than 1600 comments registered for Jolie's New York Times op-ed piece, there is little doubt about the intense public interest, which is already having a ripple effect in cancer clinics across the United States.
"With this publicity and her speaking out, I have a feeling there will be increased requests [for BRCA testing]," Sandra M. Swain, MD, president of the American Society of Clinical Oncology, told Medscape Medical News.

Angelina Jolie (REUTERS/Toby Melville)

"We already know from studies that women think they are at a higher risk of breast cancer than they actually are," said Dr. Swain, a breast cancer specialist and medical director of the Washington Cancer Institute at MedStar Washington Hospital Center.
"Hearing this, people may think, 'Oh, she's 37, maybe I also have that risk.' "
Indeed, there has already been an uptick in patient calls and emails at Moores Cancer Center at the University of California, San Diego. "People are just wondering about how to go about getting the test or more information," said Lisa Madlensky, PhD, CGC, a cancer geneticist and director of the center's Family Cancer Genetics Program, in an interview.
"I expect a lot of women are asking themselves if they should get tested or not because of a family history," said Jennifer Litton, MD, from the Department of Breast Medical Oncology, Division of Cancer Medicine, the University of Texas MD Anderson Cancer Center, in Houston.
"Overall, I think healthcare providers may expect increased questions about this testing," she told Medscape Medical News.

Assessing Risk

Unlike the average woman, who faces a breast cancer risk of about 12%, Jolie's risk before surgery was roughly 7-fold higher.
"My doctors estimated that I had an 87 percent risk of breast cancer and a 50 percent risk of ovarian cancer," wrote Jolie, whose mother was diagnosed with ovarian cancer at 46 years of age and died a decade later.
But physicians fielding questions and requests for BRCA testing from patients on the basis of a worrying family history "really need to be armed with information," said Dr. Swain.
"Primary care is going to be responsible for a lot of this, and so they're the ones who really need to be educated about what to do and not just be ordering this test on everybody. It's an expensive test, there are a lot of implications. I personally don't order the test — and I know a lot about it — so a primary care physician who really has no education in it should really not be ordering this test. I have a genetic counselor who does a full pedigree to see if they're at increased risk and need to be tested for a BRCA mutation".
"It's not something you want to automatically order," agreed Dr. Madlensky, who says that ideally, patients should be screened in primary care for red flags that might suggest the need for referral to genetic counseling — even before a test is considered.
"There are different types of BRCA testing, and knowing which one to order is a bit complicated, depending on ancestry, cancer diagnosis or not, known BRCA mutation in family or not," she said, adding that a patient's family history should not be taken at face value.
"A lot of times, the story that is in the family is not accurate. Breast cancer reporting is pretty good, but when people report they had a relative with ovarian cancer, often when we try to get those records, we find it was not ovarian but cervical or uterine or something not related to the BRCA genes."
Although there are no standardized criteria for selecting candidates for BRCA counseling, the National Cancer Institute, the National Comprehensive Cancer Network, and the US Preventive Services Task Force outline family history red flags, which generally point to first- and second-degree relatives with breast and/or ovarian cancers, especially at young ages:

2 first-degree relatives (mother, daughter, or sister) diagnosed with breast cancer, one of whom was younger than 50 years
3 or more first- or second-degree relatives (aunt or grandmother) diagnosed regardless of age
combination of first- and second-degree relatives diagnosed with breast and ovarian cancer regardless of age
first-degree relative with bilateral breast cancer
breast cancer in a male relative
combination of 2 or more first- or second-degree relatives with ovarian cancer
For women of Ashkenazi Jewish descent: any first-degree or 2 second-degree relatives on same side of family diagnosed with breast or ovarian cancer

Although Jolie has not publicly discussed the full extent of her family history beyond her mother, sources suggest that other relatives have likely been either diagnosed with similar cancers or have tested positive for the BRCA mutation.

We really ideally want the first test in the family to be on someone who's had a cancer diagnosis. Dr. Lisa Madlensky

But even if a person's history involves only 1 first-degree relative, BRCA testing "could be" appropriate in some cases, especially if that relative can no longer be tested herself, said Dr. Madlensky. BRCA testing should be viewed as a family undertaking, preferably with the cancer patient central, she added.
"We really ideally want the first test in the family to be on someone who's had a cancer diagnosis. That way, we can figure out whether cancer was result of a BRCA mutation or not. If that test is negative, then there's no need to go and test any of the other family members," she explained. "That's something most people — including physicians — are not aware of," she added.
Sometimes, discussing why a patient should not pursue testing can also be very helpful, commented Jennifer Litton, MD, assistant professor of breast medical oncology, the University of Texas MD Anderson Cancer Center.

The BRCA gene only accounts for 5% to 10% of breast cancer... Dr. Jennifer Litton

"It is important for everyone to realize and to communicate when discussing with patients that a mutation in the BRCA gene only accounts for 5% to 10% of breast cancer, and so for the vast majority of women who get breast cancer, it is not due to a mutation in this gene," she said.

Jolie's Decision

Prophylactic double mastectomy is a choice that often sparks debate, sometimes shock and disbelief, and always emotion.
"Once I knew that this was my reality, I decided to be proactive and to minimize the risk as much I could," wrote Jolie. "I started with the breasts, as my risk of breast cancer is higher than my risk of ovarian cancer."
Speaking to the New York Times, breast surgeon Susan Love, MD, said, "When you have to cut off normal body parts to prevent a disease, that's really pretty barbaric when you think about it."
But Jolie's decision was "a very, very solid choice, a reasonable choice, especially in the face of such alarming high risk of breast cancer and ovarian cancer," said Dr. Swain.
Dr. Madlensky agreed. "For someone who tests positive for BRCA mutation, its actually not radical at all. Its one of the options that is medically appropriate."
Other options for women with this mutation are medication (tamoxifen or raloxifene) or screening, "but we know screening is not preventative. It only hopes to find a cancer as early as possible," said Dr. Litton.

Eliminating Fear

For Jolie, the surgery eliminated fear. "My chances of developing breast cancer have dropped from 87 percent to under 5 percent. I can tell my children that they don't need to fear they will lose me to breast cancer," she wrote. "The decision to have a mastectomy was not easy. But it is one I am very happy that I made.... I do not feel any less of a woman. I feel empowered that I made a strong choice that in no way diminishes my femininity."
Much of the work physicians may face in light of Jolie's story will involve providing information and alleviating the kind of anxiety Jolie described — time-consuming tasks, especially because many women tend to overestimate their risk, said Mary Jane Esplen, RN, PhD, head, Program of Psychosocial and Psychotherapy Research in Cancer Genetics at Toronto General Research Institute, in Canada.
Dr. Esplen has found psychosocial oncology counseling helpful for women who cannot always accept the facts when they are told that their risk is low.
"Risk perceptions are not always based on what we might refer to as rational knowledge," she said. "We saw that just giving information alone wasn't modifying their own internal sense of risk. It had to do with family history, sometimes there were losses in families and it had to do with grief, and it had to do with this imprint that's left with a family history and the experiences associated with that."
Referring patients to genetic counseling can also be effective in diffusing anxiety, said Dr. Madlensky, debunking the notion that such counselors are hard to find.
"One of the biggest myths is that its hard to get access to a cancer genetic specialist," she said, but that is not the case. The National Society of Genetic Counselors 2012 professional status survey found that wait times for the vast majority of its members were within a 2-week period, she noted.

Cite this article: Angelina Jolie's Mastectomy: BRCA Testing in the Spotlight. Medscape. May 16, 2013.

Sunday, May 26, 2013