Shortly after Dr. Kristin Anderson was diagnosed with triple negative breast cancer at the tender age of 28, she discovered something else. Years earlier, her aunt had also had breast cancer, triggered by a faulty BRCA1 gene. Anderson had genetic testing done and learned she, too, had the exact same mutation — passed down from her Norwegian grandfather to her father and, finally, to her.
“Knowing the BRCA diagnosis, as eye-opening and emotional as it was, made decisions for treatment so much easier,” said Anderson, who now works as an immunotherapy researcher at Fred Hutchinson Cancer Research Center. “As a scientist, the way I make decisions is with data.”
For instance, Anderson chose to go through chemo before surgery to make sure her cancer would even respond to the therapy. And although her cancer presented in only one breast, she opted for a double mastectomy (with immediate reconstruction) as opposed to a lumpectomy — standard of care for a non-BRCA mutation carrier — since “the stats for breast cancer coming back in a BRCA carrier are ridiculously high.”
For Anderson, now 33, the knowledge that she harbored a genetic predisposition for breast and ovarian cancer was empowering. But not everyone in her family felt the same way. One of her cousins was open to the idea of regular screenings, but didn’t want to get tested because "knowing she had a 50 percent risk of being a mutation carrier was sufficient,” Anderson said.
As research sheds ever more light on hereditary cancers and the genes that cause them, a portion of the population is being faced with some very difficult choices. Do you test or not test? Share information about deadly mutations with relatives or keep it to yourself? Get preventive surgery or blindly hope cancer doesn’t strike?
Some people bury themselves in data; others bury their heads in the sand. And both approaches are legitimate. Cancer mutations like those in BRCA1 or BRCA2 call for tough choices. They call for individual choices. The good news is there are more and more tools to help you make them.
Are you at risk? Testing should tell
Most cancers aren’t passed down to you by your parents. They’re what’s called “sporadic,” driven not by inherited mutations but by mutations triggered by lifestyle or environmental factors such as smoking, air pollution, excessive alcohol use and obesity.
And cancers driven by mutated "BReast CAncer susceptibility genes" (we all have BRCA genes which repair damaged DNA when functioning normally) aren’t actually all that common. According to the National Cancer Institute, BRCA mutations drive about 5 to 10 percent of all breast cancers (and only represent about a quarter of all hereditary breast cancers) and approximately 15 percent of all ovarian cancers. BRCA mutations have also been linked to peritoneal, prostate and pancreatic cancers.
While Anderson found out she had a BRCA mutation after she was diagnosed with cancer, many people come to suspect they harbor a mutation because of cancer in the family. But a family history of disease is only a red flag; it doesn’t mean you have a mutation and it certainly doesn’t provide enough information to drive any health decisions.
“The biggest predictor is the mutation itself,” said Fred Hutch researcher and gynecologic oncologist Dr. Charles Drescher.
Talking to your primary care physician is one way to get the ball rolling, Drescher said. But many cancer centers also have clinics where doctors, nurses and genetic counselors provide evidence-based advice for those who harbor a harmful mutation.
“In that setting, you’ll get a multidisciplinary approach,” he said. “You’ll have your risk addressed holistically.”
A few points to keep in mind:
- If your mother, aunt, sister or grandmother has been diagnosed with breast, ovarian or another BRCA-linked cancer or a first degree male relative has had breast cancer, you may want to look into genetic testing.
- Mutations are more common in people of Ashkenazi Jewish descent as well as Norwegian, Dutch and Icelandic peoples.
- You can be tested for a single harmful mutation like the cancer-linked mutation in BRCA1 or for multiple mutations in multiple cancer-associated genes.
- Genetic testing and counseling for people at high risk is covered under the Affordable Care Act as a preventive service but do be sure to check your coverage before testing.
- The interpretation of your test really matters. If you opt for a direct-to-consumer gene test, make sure you meet one-on-one with a certified genetic counselor so you understand exactly what the test results mean for you.
Clinics for those at high risk
At Seattle Cancer Care Alliance, nurse practitioner and three-time breast cancer survivor Heidi Trott is part of the Breast and Ovarian Cancer Prevention Program, or BOCPP. Twice a month, she and a team of oncologists, geneticists and others meet with patients who have mutations such as those in the BRCA1, BRCA2, ALB2, CHEK2, BLM and ATM genes — or a harmful genetic cluster like those found in Lynch syndrome — to sort through their individual odds and options.
“Each professional will talk to them about their specific recommendations, their specific risks and what they can do about reducing those risks and when,” she said. “We also talk about lifestyle modifications.”
Drescher said individual patients’ risks will vary, depending on what mutation is found — and when.
Approximately 12 percent of women in the general population will get breast cancer during their lives. For BRCA1 mutation carriers, those odds go up to 55 to 65 percent and for BRCA2, it’s around 45 percent. As for ovarian cancers, just over 1 percent of women in the general population are diagnosed during their lives. For BRCA1 mutation carriers, the lifetime risk is around 39 percent; for BRCA2, it’s about 11 to 17 percent.
“Those numbers reflect a woman’s risk of getting a particular cancer at that particular site over the course of her lifetime,” Drescher emphasized. “When you’re making a decision about what you should do, you need to look at what your age-specific risk is, because that influences what you might do in the moment and how you think about your future and when you’ll start making decisions about interventions.”
BOCPP health care providers also talk to patients about sharing their information with others.
“I always encourage them to share this information with their family members because some families want to know,” Trott said. “If you can share what’s happened to you and what advice you’ve been given, you can say, ‘Look, we can take this into our own hands and have some control over it.’ That’s a terrific thing.”
Screening and surveillance
Actress Angelina Jolie substantially raised awareness about BRCA mutations and preventive surgeries when she went public about her double mastectomy and bilateral salpingo-oophorectomy, or BSO. Jolie underwent the surgeries as a way to avoid the hereditary cancers that killed her mother, grandmother and aunt.
Trott said preventive mastectomies are not necessarily the clinic’s “go-to” recommendation, although many "previvors" do choose to go this route.
“We don’t strongly push that, not only because of the impact psychologically and physically on the women, but because it doesn’t completely remove their risk of getting breast cancer,” she said. “Our screening — a combination of mammography and MRI — is very good at picking up early stage breast cancer. If they follow the recommended screenings, we’re comfortable with them not having prophylactic surgeries.”
Some surveillance points to keep in mind:
- Breast surveillance for high-risk women involves mammogram, MRI and clinical breast exams every 6 months.
- BRCA carriers are now advised to start getting MRIs at age 25 but not to start mammograms until they’re 30 (recommendations have changed due to new evidence regarding mammograms in younger women with BRCA mutations).
- Surveillance is key because BRCA-driven cancers are more aggressive — and sometimes harder to treat — one reason why many women opt for preventive mastectomy.
- Surveillance for ovarian cancer involves a twice-yearly pelvic exam, transvaginal ultrasound and a CA125 tumor marker (blood) test.
Trott said that if patients want to talk about risk-reducing mastectomy (which lowers the risk of breast cancer by 95 percent) they will cover the pros and cons and refer them on to a surgeon.
Chemoprevention, preventing or delaying a cancer by taking an estrogen-blocker like tamoxifen, is another possibility, she said, at least for BRCA2 carriers who tend to get estrogen receptor positive, or ER+, breast cancers. Those cancers respond well to tamoxifen and aromatase inhibitors.
“The BRCA community has not been well studied with regard to chemoprevention,” she said. “But for a patient who isn’t going to have an oophorectomy and is BRCA2 that could be an option. With BRCA1, the women tend to get ER negative breast cancers so we don’t usually recommend it for them.”
Risk-reducing surgeries
Unfortunately, screening tools for ovarian cancer have not been proven effective, although Drescher and colleagues at Fred Hutch and other institutions are working toward developing better early detection tools via the Pacific Ovarian Cancer Research Consortium.
Until then, preventive surgery to remove the ovaries and Fallopian tubes (where ovarian cancer is believed to start) is the recommendation.
“Removing both virtually eliminates any chance of an ovarian or peritoneal cancer,” said Trott. “After a risk-reducing BSO, the chance of getting a primary ovarian or peritoneal cancer is in the region of 1 to 2 percent over 20 years.”
Exactly when a woman undergoes a preventive BSO depends on her specific mutation.
- The National Comprehensive Cancer Network advises BRCA1 women to have their ovaries and Fallopian tubes removed between the ages 35 and 40.
- BRCA2 women are advised to do the same at the age of 45.
- Some premenopausal women, particularly those with BRCA2, may also choose to go through a preventive oophorectomy as a way to sidestep breast cancer (BRCA2 breast cancers are often ER+).
- Since preventive surgery stops all estrogen production and throws women into early menopause, pre-surgical counseling is highly recommended.
While some BRCA carriers feel pressure to have children right away, Trott said that’s often not necessary.
“The message, first and foremost, is live your life,” she said. “Know what your risks are and know at what point you have to do the risk-reducing strategies. Some women may feel really pressured to have children in their 20s, but they may be able to push it out further.”
She also pointed to the hereditary cancer group, Facing Our Risk of Cancer Empowered, or FORCE, as a good resource for women who are undecided about surveillance or risk-reducing surgeries. The website also offers advice for talking to your children about your BRCA status. Other resources include the BRCA Foundation, Bright Pink, Cancer Prevention Initiative, blog posts, private Facebook groups like BRCA Advanced or Beyond the Pink Moon, the National Society of Genetic Counselors, and the Society of Gynecologic Oncology which recently released their 2016 Genetics Toolkit (PDF available here).
If women do choose ovarian cancer preventive surgery, Drescher said it’s crucial to find a specialist.
“It’s a specialized procedure,” he said. “It’s not just a standard walk-in to have your tubes and ovaries removed. It’s a cancer prevention procedure and getting it done by someone with the proper expertise is important. And getting appropriate counseling is critical.”
Making choices that are right for you
Both Trott and Drescher acknowledged genetic mutations can make for some very tough decisions.
“There’s no right or wrong answer,” Drescher said. “Each woman makes an individual decision about what makes the most sense for her at a particular time. And that decision will always involve tradeoffs.”
At 33, Anderson is fast approaching the point where she needs to make her decision.
“My husband and I did some pretty intense self-reflection, individually and as a couple,” she said. “For us, it was not about ‘Do we want kids or not?’ It was ‘Do we want biological kids?’ I wrestled with this from the time of my diagnosis.”
Anderson knew that having children the “normal” way would mean that she could potentially pass on a harmful BRCA mutation (some BRCA carriers choose in vitro fertilization for this very reason).
"We decided the right plan for us is to foster and adopt," she said. "It’s a good way to maintain our timeline of doing things when it’s right for us, and it also means we can give back. There are a lot of kids that need families.”
For Anderson, knowledge represents power. It also represents hope. The cancer survivor and scientist regularly sorts through the science of BRCA in order to help others come to their own health decisions. And she spends long hours at the lab working to develop new immunotherapies for ovarian cancers, which she believes will be ready for clinical trials by the fall of 2017.
“It’s really empowering to be part of the team that is working on this,” she said. “I’m here because someone else working on the chemo drug that saved me stayed at the lab late on a weeknight or came in on the weekend. I’m motivated to pay it forward.”
Diane Mapes is a staff writer at Fred Hutch. She has written extensively about health issues for NBC News, TODAY, CNN, MSN, Seattle Magazine and other publications. A breast cancer survivor, she blogs at doublewhammied.com and tweets @double_whammied. Email her at dmapes@fredhutch.org.
