Despite Advances, Genetic Testing Remains Underutilized in Breast Cancer

Kevin S. Hughes, MD, FACS

Kevin S. Hughes, MD, FACS

Genetic testing has become more extensive, capturing a greater number of genes that confer cancer risk through broad sequencing panels. Despite these advances, which have been used to inform prophylactic and treatment strategies, genetic testing still needs to become more widespread for women with breast cancer, due in part to inadequate genetic counseling, explained Kevin Hughes, MD.

"We need to do more genetic testing to find more carriers earlier," said Hughes. "This is going to prevent a large number of cancers or [help us] identify them at an earlier or more treatable stage. Genetic testing needs to be [performed] much more than it is now."

Patients who undergo genetic testing that identifies harbored mutations associated with increased risk of breast cancer are more likely to receive optimal management strategies. For example, women with BRCA1 mutations who are at a high risk of breast cancer may be considered for a prophylactic mastectomy, Hughes added.

Additionally, as these mutations may confer risk for other cancers, such as ovarian cancer or pancreatic cancer, early identification is critical in ensuring that patients are referred to other specialties for potential intervention.

In an interview with OncLive, Hughes, the medical director of the Bermuda Cancer Genetics and Risk Assessment Clinic, co-director of the Avon Breast Evaluation Program at Massachusetts General Hospital, and associate professor of surgery at Harvard Medical School, highlighted the need for widespread implementation of genetic testing in breast cancer.

OncLive: What is the current state of genetic testing in breast cancer?

Hughes: Genetic testing for cancer is becoming more common, but it is not being used nearly enough. Most women who have a genetic mutation are not aware [they have an alteration] or have not been tested. For those reasons, they are not properly managed.

There is a real push to make genetic testing more widely available. Testing no longer needs to be done by a genetics professional; really anyone can perform genetic testing with a little bit of training and expertise. If we start testing more patients and get away from the model of a 1- to 2-hour consultation ahead of time, we can get more patients tested, identify carriers earlier, change management [strategies], and ultimately, prevent or find cancer earlier.

[Cancer] mutations are complex. There are multiple genes that can cause cancer, and different genes have different levels of risk. We need to [consider that when we're] managing patients. What mutation do they have? How old are they? What are their prior circumstances? Then, we can come up with [an appropriate management strategy].

We built a website called ASK2ME.org. ASK2ME™ is meant to help physicians [assess a patient's cancer risk]. They are able to go to that site, input the patient's age, the mutation they carry, their prior cancer and surgical histories, and the site will help determine how to manage those patients, as well as determine their risk level.

What mutations should be tested for? What modalities are available for testing?

In the past, we only tested for BRCA1/2 [mutations], which are the 2 major genes that cause cancer susceptibility. Now, the testing has become so inexpensive that we can test upwards of 40 genes for the price of testing 1 or 2 [genes] a couple decades ago.

We now do what is called panel testing, where we test for multiple genes that can cause cancer. Some people limit this to only breast cancer—associated genes, while others will test all genes. From my point of view, the more genes you test, the better because you may identify [mutations] you did not expect. I would go for the [most extensive] panel you can find. Find out what mutations a patient has, so you can manage them appropriately. Panel testing is the way to go, and bigger panels are certainly better.

If a mutation is identified, what options are available for treatment?

Each genetic mutation has a different spectrum of [associated] cancers, as well as different levels of penetrance for those cancers. An ATM mutation causes an increased risk of breast cancer, but that increased risk is relatively minor. [In that case], we might recommend MRI screening to try to find cancers earlier.

On the other hand, if a patient has a BRCA1 mutation, their risk of breast cancer is extremely high, so we consider prophylactic mastectomy and MRI. We need to look at the penetrance for each gene.

Additionally, we need to look at the other cancers that gene could cause. ATM also causes pancreatic cancer, so screening could be implemented. BRCA1 can cause ovarian cancer, and [an oophorectomy] could be considered. We need to look at the spectrum of disease for each gene, [determine] how common those cancers are for that individual gene, and then modify treatment appropriately.

We tend to use the National Comprehensive Cancer Network guidelines to tell us which genes confer higher or lower risk, as well as how to manage [patients] relative to that risk.

What challenges regarding genetic testing still need to be addressed?

The biggest challenge with genetic testing right now is that it is not being done appropriately or often enough. The need for genetic counseling prior to testing is a barrier because it's not feasible; we don't have enough genetic counselors to counsel these patients. We can't spend 1 to 2 hours talking about a test before doing the test. We need to remove that barrier and get more people to perform genetic testing, including primary doctors, obstetricians/gynecologists, and surgeons. All of us need to be performing more genetic testing.

If you get a result back that you do not understand, then bring in a specialist—–figure out who the patient needs to be referred to.

No [1 person can effectively manage a patient with a] BRCA1 [mutation]. A BRCA1 carrier needs to see a breast surgeon for prophylactic mastectomy, a radiologist for MRIs, and a gynecologic oncologist for a potential oophorectomy. Patients require somebody to act as a navigator to say, "With this mutation, you need to see this specialist," and get them on a management plan.

How could the use of genetic testing affect the future of targeted therapy?

With BRCA1/2, we are now looking more toward PARP inhibitors a [treatment] modality for patients. We are going to discover more agents that are targeted to genetic mutations.

The FDA has now approved several drugs for specific mutations regardless of the cancer site. Our old approach of treating by organ system will eventually be replaced by treating by genetic defect; that will occur regardless of what the tissue of origin is.

What research are you looking forward to in the breast cancer space?

We've done very well in getting rid of mastectomy and axillary lymph node dissection. We have [de-escalated] treatment for eligible patients. I am looking forward to [continuing this trend] and implementing less treatments for patients. Already, we try not to radiate women over the age of 70 years with small, early cancers. We are giving less chemotherapy when their genomic profile indicates low-risk disease.

In the short term, [I am looking forward to] decreasing the amount of treatment and deriving the same impact. Ultimately, the goal is to cure patients' cancer with minimal treatment.