If your mother or sister had breast cancer, you may wonder if you are next. It’s a sobering question, and one genetic researchers are trying to explore.
Looking at your family tree and examining your DNA can help doctors determine whether you have a genetic predisposition for breast cancer. In genetic testing, blood, saliva or tissue samples are used to look for changes in genes or chromosomes called mutations. Inherited mutations contribute to about 10 percent of all cancers, according to the National Cancer Institute.
Inherited breast cancer
In general, about 5 to 10 percent of breast cancers are caused by inherited single gene mutations, said Talia Donenberg, a board certified genetic counselor who specializes in oncology at Sylvester Comprehensive Cancer Center at the University of Miami.
The National Cancer Institute estimates that 55 to 65 percent of women who inherit a BRCA 1 mutation will develop breast cancer by age 70. For the BRCA 2 mutation, 45 percent of women who inherit this will develop breast cancer by 70.
“In the general population, a woman has a 10 to 12 percent of getting breast cancer in her lifetime,” Donenberg said. “BRCA carriers have a 60 to 80 percent of getting breast cancer over their lifetime, depending on the study you look at. BRCA 1 and 2 are known as the highest-risk genes.”
Women from the Bahamas have a higher risk than the general population, as well as Ashkenazi Jews of Central or Eastern European descent.
“We’ve done many years of study at the University of Miami through the Bahamas, and we’ve uncovered a very high incidence of hereditary breast cancer due to BRCA 1 and 2 mutations in the Bahamas. The highest incidence in the world, actually,” Donenberg said.
In the Ashkenazi Jewish population, about 12 percent of breast cancer is due to BRCA 1 and 2 mutations, she said. In the Bahamian population, about 24 percent is due to BRCA mutations. “It’s a very small population down there, and there is geographic and reproductive isolation,” Donenberg said.
Studies have been done in other Caribbean islands, and while a higher incidence of breast cancer was found in Trinidad, it was not due to specific mutations like in the Bahamas or the Ashkenazi populations, she said.
Genetic testing referrals
Patients are typically referred for genetic testing by their doctor or after breast imaging. Most referrals are breast cancer patients sent by their surgeon or oncologist, Donenberg said.
Dr. Adriana Milillo-Naraine, a breast oncologist at Memorial Cancer Institute at Memorial Hospital West in Broward, said she meets with a patient to review the family tree and what family members have been affected.
“If there are red flags, I will refer them to a genetic counselor, who will determine what type of testing to do,” she said. “We choose the testing panel that fits the patient.”
There also are National Comprehensive Cancer Network guidelines for who should be referred. They include:
▪ A family history of early-onset cancer, diagnosed before age 50.
▪ A family history of two or more members on the same side of the family with breast cancer.
▪ A family history of ovarian cancer.
▪ Male breast cancer.
▪ Bi-lateral breast cancer.
Dr. Jeff Boyd, director of genomic medicine at Baptist Health South Florida’s Miami Cancer Institute, said it’s a different conversation with every woman. “That’s why genetic counseling is so vitally important,” he said. “The average woman walking down the street has a perceived risk of dying of breast cancer that is much higher than it actually is.”
Testing in families
It’s always best to test an affected individual in the family, someone with the type of cancer related to the syndrome you have in question, Donenberg said. “If you have relatives living with breast cancer, it’s best to test the person diagnosed at the earliest age,” she said. “So if you have an aunt who was diagnosed at 75 and a sister diagnosed at 35, you would want to test your sister.”
In families, first-degree relatives have a 50 percent chance of inheriting a mutation, Donenberg said. So if a parent carries a mutation, there’s a 50 percent chance for each child. For adult-onset cancers like breast cancer, testing would begin at age 18 or older.
Testing facilities and cost
Forget about home tests or tests you find online. Consult a board-certified genetic counselor, or a facility with a cancer genetics program, with experts to supply counseling and assessment, Donenberg said.
The costs can be covered by insurance, depending on the individual and insurance. The price typically ranges from $250 to $1,500, depending on the lab, she said.
Boyd said there are a lot of gray areas in testing results. “There are five levels. It’s not just good or bad,” he said. “The test results are complex, so post-counseling is critical.”
If you test positive for a genetic mutation, “the next question is, ‘What are we going to do about it?’” Milillo-Naraine said. “We can come up with a treatment plan, like adding a breast MRI to their screenings.”
In post-counseling, the patient learns what the results mean and what interventions, such as medication or risk-reducing surgery, are recommended.
The Angelina Effect
“The Angelina Effect,” the so-called phenomenon after actress Angelina Jolie’s 2013 announcement that she carried the mutated BRCA 1 gene, created more awareness about genetic testing.
“Here was a well woman with a mother who died of cancer at an early age who found a BRCA gene mutation. She is in a class we call ‘previvors,’” Boyd said. Jolie ultimately had a risk-reducing mastectomy and removal of her ovaries and fallopian tubes to lower risk of breast and ovarian cancers.
“The Angelina Effect raised awareness, but it is a double-edged sword,” he said. “It increased the average woman’s perception that her risk of dying of breast cancer is significantly higher than it actually is, which is not particularly helpful.”
That perception takes the focus off things that are more likely to affect a woman’s health, such as obesity and a healthy lifestyle, he said.
Creating targeted therapies
Examining the genetic architecture of tumors helps develop therapies that are targeted and personalized, Boyd said. “Targeted drugs can be used to treat tumors with specific mutations in a woman with cancer,” he said. For example, targeted therapies like PARP inhibitors are being used in breast cancer patients with the BRCA mutation to generate longer-lasting and more effective responses, Boyd said.
Doubts about testing
Some patients don’t want to be tested because they’re afraid of losing lose their job or insurance. It’s important for patients to know that the Genetic Information Nondiscrimination Act, or GINA, protects them from discrimination due to genetic information, Milillo-Naraine said.
Other patients shy away from testing because they don’t want to hear bad news.
“The importance of doing the genetic testing is if you find that you have a mutation, there are things we can do to prevent cancers from occurring,” she said. “I think the majority of patients would want to prevent cancer, rather than having to deal with it.”