As genetic testing becomes more advanced — and, in some cases, easy enough to do in your own home — more people have been able to learn whether they carry gene mutations linked to an increase in cancer risk. There are several gene mutations that signal an inherited predisposition to cancer, but among them, mutations in BRCA1 and BRCA2 have gained particular notoriety.
We can, in part, thank celebrities for that, starting in 2013 with actress Angelina Jolie announcing her decision to undergo a preventive double mastectomy after learning she had the BRCA1 mutation. Most recently, influencer Alix Earle shared on her Netflix series “Earle Meets World” that she is a carrier of a BRCA2 mutation.
An estimated 1 in 250 to 500 Americans have a BRCA1 or BRCA2 mutation — what’s referred to in the medical lingo as a “pathogenic variant.” Crucially, BRCA mutations affect women and men, and either can pass a BRCA gene mutation on to their children.
There is a higher incidence of BRCA mutations in certain populations, like those with Ashkenazi Jewish ancestry, but our understanding of which populations are most affected is somewhat limited by disparities in testing. For example, one large study showed that Asian, Black and Hispanic patients were less likely to obtain genetic testing after a cancer diagnosis than non-Hispanic White patients.
And while many more people are getting tested and learning they carry these genetic variants, experts believe that hundreds of thousands of Americans may be born with them but not know it.
So, what exactly is BRCA? How does a BRCA1 or BRCA2 mutation increase your risk for cancer? And when should you consider genetic testing? Here’s what you need to know.
What the BRCA1 and BRCA2 genes do
Everyone is born with two copies of both BRCA1 and BRCA2, which are genes involved in the DNA repair process. While they are physically far apart in the human chromosome, they share a similar function and were both first linked to breast cancer — thus named “BReast CAncer gene 1” and “BReast CAncer gene 2,” in the order of their discovery in the 1990s.
“They’re like Band-Aids. They come and fix injuries to our genes,” said Mary Daly, founder and director of the Fox Chase Cancer Center’s risk assessment program. When one copy of either BRCA1 or BRCA2 is mutated, it leaves the DNA more vulnerable to damage. And when the DNA can’t adequately repair itself, it leads to higher rates of certain kinds of cancers, including breast, ovarian, pancreatic and prostate cancer.
It’s important to note that these mutations give a person a predisposition to cancer; they don’t cause the disease, said Tuya Pal, professor of medicine and associate director for clinical genomics at the Vanderbilt Ingram Cancer Center. “Some people with BRCA mutations will not develop cancer. The majority, based on current assessments, especially women, will develop cancer in their lifetime. But it’s not 100 percent,” Pal said.
The types of cancer linked with BRCA1 and 2 mutations
Mutations in BRCA1 and 2 are both strongly associated with the development of breast cancer (including in males, though risk is lower than in females) and ovarian cancers. Both are also associated with pancreatic and prostate cancers, though this risk is higher and more well-established with BRCA2 mutations than BRCA1, said Pal.
There has been speculation about the association with other cancers — such as stomach cancer — but these links are not well-established, so there currently aren’t recommendations for people with known BRCA1 and BRCA2 mutations to undergo screening, Pal said.
The degree of risk, specific subtype of cancer you may develop and typical age of onset vary depending on whether you carry a variant in BRCA1 or in BRCA2.
For example, one recent study estimated that a woman with a BRCA1 mutation has a 56.8 percent chance of developing ovarian cancer between the ages of 30 and 80, compared with a 25.4 percent chance in someone carrying a BRCA2 mutation. The cancer also tends to be diagnosed younger with a BRCA1 mutation.
Lifestyle, family history and the specific genetic variant a person carries (a gene can mutate in several ways) also play into a person’s likelihood of developing cancer. “In my practice, and I think for a lot of us [doctors], we’re doing more personalized risk [assessments], so we’re layering on the other information,” said Pal. The medical community continues to refine this approach to assessing risk as we learn more about all of the factors that contribute.
Family history is crucial for testing
On her show, Alix Earle said that she and her sister, Ashtin, both tested positive for a BRCA2 gene mutation after their mom was diagnosed with breast cancer and tested positive herself. That’s called cascade testing, when a family member tests positive for a pathogenic variant in a gene, and first-degree relatives then get referred for testing themselves.
If that first-degree relative then tests positive, their first-degree relatives would then get tested — for example, if Alix were to have children, her genetic counselor would probably recommend that the kids undergo testing once they’re adults.
Certain cancer diagnoses automatically trigger a referral for genetic testing. For example, anyone with pancreatic, ovarian, aggressive prostate or certain kinds of breast cancer — like male breast cancer or breast cancer diagnosed under 50 years old — should be referred to test for several inherited mutations in cancer predisposition genes, including in BRCA. The results of these tests are not only important for family members and prevention of future cancers, but they may also play a role in treatment depending on the cancer type.
However, you don’t have to have a personal cancer diagnosis or a known BRCA mutation in your family to be tested. Family history of any of these associated cancers is a warning sign for a possible BRCA mutation, said Daly, “and that’s often what brings people in.” Other red flags in your personal or family history include multiple cancers in the same person and early-onset cancers.
If you look at your family tree and notice a lot of cancer, it makes sense to speak with a genetic counselor. They can help you parse out whether you should pursue genetic testing to check for a mutation in BRCA or other genes.
One important caveat is that current guidelines for who should receive genetic testing may miss a substantial group of people who might carry a mutation like BRCA and should get tested. This is an active and important area of research.
With that in mind, the National Comprehensive Cancer Network counsels that certain populations of people, such as those of Ashkenazi Jewish heritage (where 1 in 40 individuals carry specific BRCA1 or 2 mutations), may consider cancer genetic testing and counseling even without a personal or family history of cancer.
While health insurance usually covers genetic testing and subsequent follow-up screenings, at least for people who meet the NCCN-testing guidelines, this is not always the case. For example, Medicare may deny coverage for preventative screenings in those with known cancer-predisposition genetic mutations but without a cancer diagnosis, said Pal.
Next steps if you test positive for a BRCA mutation
Testing positive for a pathogenic variant in BRCA1 or BRCA2 usually means referral to a specialized genetics team that can see you regularly and provide counseling on next steps.
For women, that involves more intensive breast screening beginning at age 25, with consideration of a risk-reducing mastectomy, and salpingo-oophorectomy, or surgical removal of the ovaries and fallopian tubes. Because ovarian cancer typically occurs later in patients with BRCA2 mutations than with BRCA1 mutations, practitioners generally recommend considering removal of the ovaries and fallopian tubes earlier in BRCA1.
Part of the challenge is that no good screening for ovarian cancer currently exists, which is why removing the ovaries — which has significant implications in terms of fertility and the consequences of inducing premature menopause — is recommended to be considered.
For men with a BRCA mutation, screening involves an annual prostate-specific antigen blood test, with possible integration of a baseline prostate MRI and consideration of mammograms — with stronger recommendations in BRCA2 than in BRCA1.
Doctors recommend pancreatic cancer screening in anyone with BRCA2, generally starting at age 50 (or earlier depending on family history), and in BRCA1 mutation carriers with family histories of pancreatic cancer.
Detecting a BRCA mutation early, and starting the recommended screenings, can be lifesaving. “We can do a lot in terms of managing the cancer risk,” said Pal. However, not everyone has equal access to genetic testing and subsequent counseling and screenings, she said. “When we’re talking about expanding genetic testing access, I think it needs to go hand in hand with ensuring that everyone that is identified to have a mutation gets the care that they need, and ideally at no cost.”
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