A Difficult Decision
BRCA genes and taking preventive action against breast and ovarian cancers
On May 14, 2013, newspaper and magazine headlines swirled with stories about Angelina Jolie. This was not typical tabloid fodder; on that day, she announced in a New York Times op-ed that she carried a defective copy of the BRCA gene, which her doctors estimated had increased her chances of developing breast and ovarian cancer to an alarming 87 percent and 50 percent, respectively.
“Once I knew that this was my reality, I decided to be proactive and to minimize the risk as much I could,” she wrote.
Continuing on, Jolie wrote that she decided to have a preventive double mastectomy, which she said decreased her chances of developing breast cancer to less than 5 percent. Her surgery was fueled from a genetic test that revealed a mutation in BRCA1, one of two breast cancer susceptibility genes.
“Everybody has these genes,” explains Kate Wilson, director of Cancer Genetic Counseling Services at The University of Texas Health Science Center at Houston (UTHealth) Medical School. “The reason they're named BRCA1 and BRCA2 is because they're two different areas of our DNA, or our genome. Typically, if somebody has a mutation, it's either one or the other. Both the BRCA1 and BRCA2 are associated with an increased risk for breast and ovarian cancers.”
Wilson explains that when these genes are working correctly, their job is to stop cancer from happening. “When there's a change or a mutation in one of the genes, it opens the door for cancer to occur and lowers the threshold for cancer to happen,” she says, adding that having a BRCA mutation means you have a hereditary predisposition to getting breast and ovarian cancers.
The breast and ovarian cancer risk for women who carry either a BRCA1 or BRCA2 mutation is significantly higher than for women without a BRCA gene mutation. Wilson says the main difference between the two genes is that someone with a mutation in BRCA1 has a higher risk for ovarian cancer than someone with a mutation in BRCA2.
Who should get tested?
It is estimated that only 1 in 500 women will be a carrier for a BRCA mutation. “That number does increase if a woman has an Ashkenazi (Central and Eastern European) Jewish background,” Wilson says. “They have about a 1 in 40 chance of having a BRCA change.”
It also should be noted that only about 5 percent of breast cancers and 10 to 15 percent of ovarian cancers are due to a BRCA gene mutation. “Most breast cancer, 80 to 90 percent, is sporadic,” Wilson says. “It happens by random chance and is not due to a BRCA mutation.”
Because we inherit copies of our genes from our parents, it's possible that the mutated BRCA gene can come from either parent.
“We have one copy of the BRCA gene that's working fine, but if you get one copy that's not working from either mom or dad, there’s a mutation,” Wilson explains. “When you have children, you are either going to pass on the copy of your gene that works or the copy that doesn’t.
“Each time a BRCA carrier has a child, they have a 50-50 chance of passing on the copy that doesn't work,” she continues. “That means that each of their children will have a 50-50 chance of having this increased risk.”
Wilson says that women who want to find out if they are positive for a BRCA mutation may undergo BRCA genetic testing.
“Testing can either be done with a saliva sample, like a mouthwash sample, or a blood sample. Both have the same accuracy,” she says. “It basically goes up and down the links of both the BRCA1 and BRCA2 genes, and it's looking for mutations, changes or anything that doesn't make sense or causes the gene not to work. If it's positive, that means that somebody does have a change and is a carrier.”
Currently, BRCA genetic testing can cost anywhere from several hundred dollars to as much as $4,000. Wilson says if an individual is at risk for having a BRCA mutation, insurance is likely to cover it. However, different insurance companies can have different criteria to determine who is at risk. Therefore, those individuals considering this test should first check with their insurance company about coverage options.
So, how do you find out your risk to help you decide whether or not to have this costly test?
“We generally think about doing the test on women who have been diagnosed with breast cancer younger than 60, or if they have been diagnosed with ovarian cancer,” Wilson says. “If it's somebody who has never had cancer, we look to see if they have a significant family history of breast or ovarian cancer. Women who are Ashkenazi Jewish and have had a relative with breast or ovarian cancer may be enough for them to be tested.”
Weighing all options
Once it's determined you have a defective gene, the next step is to meet with a genetic counselor to go over the results of the testing and what they mean. “We then try to get them to meet with an oncologist and a surgeon to talk about all the different options, like surveillance versus surgery, and help them figure out which decision is best for them,” Wilson says.
One treatment option for women with a BRCA change is to have, like Jolie, a preventive double mastectomy. To help determine if this is the right choice for her, a woman might meet with a surgeon like Emily Robinson, MD, associate professor of surgery at UTHealth Medical School, to discuss the pros and cons of having this procedure.
“It's the most effective way of preventing development of breast cancer,” Robinson says. “You can reduce your relative risk anywhere from 89 to 100 percent.”
A major con, Robinson says, is the cosmetic issues associated with the double mastectomy and the multiple procedures a patient may have to endure before she's happy with her results.
“Even though surgeons can do immediate breast reconstruction, where you will wake up with a breast mound in place, you may still have multiple procedures that happen after the initial reconstruction,” she adds.
For example, Robinson says the areola may have to be tattooed on and the nipple reconstructed. Some body fat may be added to the breast mound from liposuction to make the contour exactly right.
“If the patient decides on mastectomy, it's important to visit several surgeons and several plastic surgeons and make sure they're comfortable with their team,” Robinson says.
She notes that some patients still may develop breast cancer, even if they choose mastectomy. It also does nothing to reduce the risk of ovarian cancer, she adds.
Robinson says there are two reconstructive options with mastectomy — reconstruction with implants (silicone or saline) or reconstruction with the patient's own tissue.
“The newer, fifth generation silicone implants are now FDA-approved, and their consistency is more like a gummy bear than liquid,” she says. “They're actually better, as far as a more natural feeling of a breast, than saline implants.”
One possible downside to the procedure is that it's recommended the implants are changed every 10 years.
“When you're putting implants underneath skin as opposed to underneath breast tissue, it's really a much different cosmetic look in terms of overall effect,” Robinson says. “It's not like a breast augmentation; it's not quite as good.”
Tissue for breast implants most commonly comes from the abdomen, Robinson says, so the patient, in effect, can get a tummy tuck at the time of the operation. “If the patient doesn't have enough tissue there, or if they've undergone multiple procedures before, some plastic surgeons can take it from the gluteal region or the inside of the thigh,” she adds.
Should a woman choose not to remove her breasts, she has other alternatives, including more frequent breast screenings.
Increased screenings mean the patient does monthly breast self exams. At three to six months, the patient has physician-assisted breast exams. Lastly, the patient has a mammogram and an ultrasound alternating with a breast MRI every six months.
“The thought behind that is screening more often and in different ways to try to catch something as early as possible,” Wilson says.
Still, there are downsides to this option, including the number of office visits a patient needs, and the fact that a patient can present with cancer that develops within the six months between imaging, Robinson notes.
Using chemotherapy as prevention is a second option to mastectomy. “The only medication that's approved or known to be efficacious is tamoxifen, an anti-estrogen medication,” Robinson says. “Its effectiveness is primarily for patients with BRCA2 mutation, because their tumors are estrogen-receptor positive and tamoxifen blocks the estrogen-receptor. So, it's not recommended to reduce the breast cancer risk for BRCA1 mutation carriers.”
A final option is an oophorectomy, removal of the ovaries. “An oophorectomy can reduce the risk of breast cancer by up to 50 percent,” Robinson says, adding that an oophorectomy is recommended if the patient is at least 35 years or older and is finished childbearing.
Additionally, an oophorectomy is a good surgical option for a woman with a heightened risk of ovarian cancer due to the gene mutation. “That does significantly decrease the risk for ovarian cancer, which is harder to screen for,” Wilson says.
If an oophorectomy is not an option, Robinson says there is screening with ultrasounds, CA 125 blood tests and pelvic exams. She cautions, though, that ovarian cancer is really difficult to detect. “For most patients, once they're of a certain age and finished childbearing, the general recommendation is to go ahead and get the oophorectomy,” she says. “Besides surveillance, that's the only option.”
Robinson adds that both preventive surgery and surveillance options are covered by most insurance plans, but as with BRCA genetic testing, patients should first check with their insurance company.
Jolie decided to openly discuss her preventive double mastectomy in an effort to increase awareness about the BRCA gene mutation and to help others.
“I choose not to keep my story private because there are many women who do not know that they might be living under the shadow of cancer,” she wrote in her op-ed. “It is my hope that they, too, will be able to get gene tested, and that if they have a high risk they, too, will know that they have strong options.”