This lesser-understood factor can signpost a greater risk of developing the disease.
All October, we’ll been unpacking as much useful info as we can about breast cancer — from how to perform your own breast exam to the most common forms of breast screening to how radiation affects the body to advice from people who’ve been through it. But is there any way of knowing how likely we are to develop breast cancer? While individuals can’t know this for certain, there are factors that can increase the probability we’ll experience the disease at some point. One of these is our genetics.
We’ve spoken to experts on the BRCA gene, which can be a major indicator of our predisposition to breast cancer, to help unpack this lesser-understood variable.
How significant is genetics as a predictor of breast cancer?
It’s significant, but far from the whole story. “Five percent of women and 10 percent of men with breast cancer have a specific genetic susceptibility,” explains Susan Domchek, MD, executive director of the Basser Center for BRCA at the University of Pennsylvania’s Abramson Cancer Center. This susceptibility is indicated by mutations in our BRCA1 and BRCA2 genes.
“Everyone has BRCA1 and BRCA2 genes,” explains Dr. Domchek. “These genes make proteins that help repair DNA damage in the cell. If an individual is born with a bad copy — otherwise known as a mutation or pathogenic variant — in BRCA1 or BRCA2, they have an increased risk of developing cancer, specifically breast, ovarian, pancreatic, and prostate cancer.”
Though most people with breast cancer have no genetic susceptibility to the disease, if you are born with a genetic predisposition to it, your likelihood of experiencing it is greatly increased.
The risk of developing breast cancer if you have a BRCA gene mutation
“If a woman has a BRCA1 mutation, her risk of developing breast cancer is approximately 70 percent, and her risk of ovarian cancer is 45 percent,” explains Dr. Domchek. “For women with a BRCA2 mutation, the risk of breast cancer is 70 percent, and for ovarian cancer, it’s 20 percent. Mutations in these genes — particularly BRCA2 — are also associated with an increased risk of male breast cancer, pancreatic cancer, and prostate cancer.”
Additionally, a 2023 study found that individuals who have a BRCA1 or a BRCA2 mutation also have increased risk of developing other cancers — namely endometrial, esophageal, gastric, testicular, and urinary tract cancers.
It’s important to remember though that only about six percent of breast cancers are a result of inherited mutations in the BRCA1 or BRCA2 genes.
Other genetic mutations that can cause breast cancer
While there are other genetic mutations that can signpost a predisposition to breast cancer, these still only account for a relatively small number of patients.
“A smaller percentage of breast cancers may be caused by mutations in other genes, like PALB2, PTEN, ATM, and CHEK2,” says Jane Lowe Meisel, MD, medical director for the JScreen Cancer Program. “Genetic mutations can be a predictor of breast cancer risks, but the vast majority of patients diagnosed with breast cancer do not have an inherited cancer-causing gene mutation that we can identify.”
Is there anyone for whom BRCA1 and BRCA2 testing is especially important?
“Individuals with a family history of breast cancer before the age of 50, male breast cancer, ovarian cancer, pancreatic cancer, or advanced prostate cancer have an elevated risk of having a BRCA mutation, and genetic testing should be offered to them,” says Dr. Domchek. “Individuals of Ashkenazi Jewish descent also have a 1 in 40 chance of having a BRCA1 or BRCA2 mutation, compared to 1 in 200 in the non-Jewish population.”
Even if you’ve already been diagnosed with breast cancer, BRCA testing can offer useful insights that can inform the kinds of treatment that may be most effective for you.
“It’s important for patients with stage 4 breast cancer that is either hormone-receptor-positive or triple-negative to undergo genetic testing,” explains Dr. Meisel. “If these patients have BRCA mutations, they may be offered novel treatments for the management of their metastatic breast cancer. The drugs olaparib and talazoparib were approved for this purpose.”
How does this form of genetic testing work?
“Genetic testing is done from a blood or saliva sample which is sent to the lab,” says Dr. Domchek. “It’s important to review your family history with a genetic counselor or another provider, to make sure that the appropriate genetic testing is done.”
As nerve-wracking as the process may be, forewarned is forearmed, and having all the possible information about your genetic predisposition to cancer available is incredibly useful.
“Those who learn about an inherited BRCA1 or BRCA2 gene mutation before a diagnosis of cancer have an opportunity to do enhanced screening for breast, pancreatic, prostate, and ovarian cancer,” explains Dr. Meisel. ”This enables them to find cancer at an earlier, more easily treatable stage. It also allows women with mutations to plan preventative surgery for breast cancer, such as a bilateral mastectomy, or removal of both breasts, and/or ovarian cancer, like bilateral salpingo-oophorectomy, or removal of the fallopian tubes and ovaries, should they wish to.”
Are there any risks to this form of screening?
“They can show changes in the genetic code called ‘variants of uncertain significance,” says Dr. Domchek. The impact of these changes on the proteins that repair DNA damage in the cell is unknown, and therefore, so is their effect on a patient’s susceptibility to breast cancer. “This can be very challenging for patients and providers,” adds Dr. Domchek.
It’s also important to understand in advance what the impact of a positive test might be. “For example,” says Dr. Domchek, “if a woman has a BRCA1 mutation, she will be strongly encouraged to have her ovaries removed by age 40.”
Aside from the lightheadedness, bleeding, or bruising that can come from a blood draw, there is no medical risk associated with being tested for a BRCA mutation. However, as Rick Baehner, chief medical officer of Precision Oncology at Exact Sciences explains, based on a person’s test results, there may also be emotional implications to testing.
“If a person tests positive, this may cause feelings of anxiety or fear,” he says. “Alternatively, if a person tests negative, there may be a feeling of ‘survivors’ guilt’ for testing negative while other family members have a known mutation. There also may be a need to discuss their results with their family members, so that they can decide if they would like to undergo genetic testing.”
So, you’ve discovered a BRCA1 or BRCA2 mutation, what happens next?
If genetic testing has identified a mutation indicating a greater risk for breast cancer, then the next step is screening for cancer itself. “The results of a BRCA test may help inform a person’s action plan to screen for cancer,” explains Dr. Baehner. “Women with BRCA mutations should seek the guidance of a certified genetic counselor to help understand their results and the medical implications.”
We’ve broken down the basics of mammograms, and when women of average risk should start to think about getting them, here.
