Are the Guidelines for Breast Cancer Genetic Testing Out of Date?
In a new study, researchers say more women should be tested for breast cancer genes. However, not everyone is so sure.
Knowing if you have a gene mutation can help you take preventive action against breast cancer.
Inheriting certain genetic mutations from your mother or father can raise your risk of breast or ovarian cancer.
Knowing you have this type of mutation allows you to take preventive measures as well as help guide screening and treatment.
In the United States, more than 300,000 people receive a breast cancer diagnosis every year. Heredity is involved about 10 percent of the time.
But some women have no idea they’re at increased risk.
They haven’t been tested because they don’t meet current testing guidelines.
In fact, researchers in a new study published in the Journal of Clinical Oncology say guidelines for who should get tested are out of date and should be changed.
What the study found
The National Comprehensive Cancer Network (NCCN) testing guidelines were developed 20 years ago to identify carriers of the BRCA1 and BRCA2 genetic variants.
Over the years, changes have been made in who should be tested and currently include BRCA1/2, TP53, and PTEN.
The researchers evaluated current guidelines to identify patients with breast cancer with pathogenic variants in expanded panel testing.
The multi-center prospective registry included community and academic sites with experience in genetic testing for cancer.
Patients included women 18 to 90 years old who had new or previous diagnoses of breast cancer. None had genetic testing before.
Of 959 women, almost 50 percent met NCCN criteria.
All were given an 80-gene panel test.
Overall, slightly less than 9 percent had a pathogenic/likely pathogenic (P/LP) variant.
Among those who met NCCN guidelines, slightly more than 9 percent had a P/LP variant. For those who didn’t meet the guidelines, almost 8 percent had a P/LP variant.
The difference in positive results between these groups wasn’t statistically significant.
The researchers say almost half of women with a P/LP variant are missed under current guidelines.
They recommend that all patients with a diagnosis of breast cancer undergo expanded panel testing.
How this relates to guidelines
Dr. Banu Arun is professor in the department of breast medical oncology at the Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center.
She told Healthline that the current guidelines for breast and ovarian cancer were developed for BRCA1 and BRCA2 mutations and are quite accurate.
“The study showed that if you fit the criteria for BRCA tests, you’re most likely positive. If you don’t fit, the positive rate is low,” said Arun.
Study authors suggest that all women should get expanded testing, but Arun finds that hard to say based on this paper.
“They tested for other genes and did find a number of patients who were positive for other genes. But they did not report on the family history of these patients. Maybe with evaluation, they would have been tested for those genes,” she said.
“They found a high rate of variants of uncertain significance,” she continued.
Arun explained that we don’t yet know what impact that knowledge has in terms of screening and risk reduction.
“Other studies should confirm whether the positive rate is high in everyone or some of these people had a significant family history of other cancers. Other studies looking at guidelines plus family history as a component might be very helpful,” said Arun.
Family history often a mystery
Current guidelines have to do with personal history of breast or ovarian cancer, age at diagnosis, having triple-negative breast cancer, or being of Ashkenazi (Eastern European) Jewish ancestry.
Also included is a family history of cancer.
Sandra M. Brown, MS, LCGC, is manager of the cancer genetics program at The Center for Cancer Prevention and Treatment at St. Joseph Hospital in California.
She told Healthline that many people are unaware of family history beyond grandparents.
Genetic mutations that increase the risk of breast cancer don’t always show themselves in every generation of a family’s history.
“When we think about NCCN guidelines requiring family history, sometimes it’s impossible. Twenty-five percent of the time the lines are coming through men who pass it on but usually don’t develop breast cancer,” she explained.
Brown said that it’s random whether a father inherits the mutation and his sister doesn’t.
Anyone concerned about their family history should talk to a genetic counselor and have a risk assessment done, she advised.
How tests can be used
What does genetic testing have to do with prevention and treatment?
“It’s a big deal and it depends on the gene,” said Brown.
Each mutation has a specific window of risk and a lot depends on your age.
According to Brown, a 35-year-old-woman with BRCA-associated breast cancer has a 50 percent risk of developing a second primary cancer in her lifetime. And she has a lot of life ahead of her.
For a 70-year-old, the risk is about 15 percent.
That’s why someone younger might choose a bilateral mastectomy instead of lumpectomy with radiation. Doing so can reduce their lifetime chance of a second primary breast cancer.
It can also affect other forms of treatment.
“Knowing the genetic mutation tells about the behavior of the cancer and the possibility of treatment with targeted therapies,” said Brown.
But it’s important to interpret the results correctly.
Genetic testing can get complicated.
“The more genes you analyze, the more likely you are to identify a variance of unknown significance. It’s difficult to explain the meaning of some genetic variations to the patient. If a patient is concerned about one of these, it might be something they give value to that we would hope they wouldn’t. Gray areas are disconcerting,” she explained.
And you can’t necessarily define all the consequences in an individual.
“Genes behave in concert with other genes in a unique environment in your body. What you inherit and your lifestyle change how risk might manifest. It’s hard to base testing guidelines on so much randomness,” she said.
“Bilateral mastectomy is now considered overdone in moderate-risk patients. But in high-risk BRCA patients, we see quality of life improve. We want the right amount of response or diligence about screening without overdoing it,” said Brown.
Ideally, you want to test the affected person in the family because they have the highest likelihood of mutation, said Arun.
“Once a mutation is identified, then do cascade testing. Test family members for that specific mutation,” she said.
Arun explained that if a woman with cancer is negative, you run the risk that it’s not a true negative. There may be other genetic mutations we don’t know about yet.
But if a woman with cancer tests positive for mutations and her unaffected sister tests negative for those mutations, that’s a true negative.
Current guidelines don’t recommend genetic testing for everyone. Insurers tend to follow these guidelines when deciding which tests to cover.
While they once cost thousands of dollars, the price has dropped to about $250.
And direct-to-consumer genetic testing is becoming increasingly popular.
Testing without professional guidance, though, can leave the door open for misinterpretation.
“Discussion of risk is important and needs to take place with a genetic counselor,” said Arun.
The current guidelines serve a purpose, said Brown, noting that genetics is a rapidly changing field.
There are genetic mutations that haven’t yet been identified or become clinically available. Concerned patients should look for updated testing after three to five years.
Brown’s big concern is maintaining quality.
“We vet the laboratories and their methods of interpreting test results. It’s not enough to say we found something. There’s a clinically valid way of interpreting lab results and some testing is not clinically valuable,” said Brown.
She stresses the need to work with a qualified genetic counselor.
“Our job is to make sure risks and benefits are understood so women can make a better choice for themselves. Women engaged in decision-making feel more confident and have less regret,” said Brown.
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