Expert Explains Intricacies of Molecular Testing in Ovarian Cancer

Sarah E. Taylor, MD

All patients with ovarian cancer should receive somatic and germline testing upon diagnosis—providing insurance covers the cost—to create more personalized treatment approaches, according to Sarah E. Taylor, MD.

“Every single woman with ovarian cancer should undergo genetic testing. It has huge implications for her and her family,” said Taylor, an obstetrician-gynecologist and oncologist in the Magee Gynecologic Cancer Program at the University of Pittsburgh Hillman Cancer Center. “Somatic testing is definitely available and should be utilized to help with guiding additional therapeutic interventions for our patients. Genetic counselors should be an integral part of all the work we do for patients.”

In an interview during the 2019 OncLive^® State of the Science Summit™ on Ovarian Cancer, Taylor discussed the role of somatic and germline testing for patients with ovarian cancer and their family members to create more personalized treatment and prevent disease.

OncLive: Could you provide an update on molecular testing in ovarian cancer?

Taylor: Molecular testing in ovarian cancer involves looking at germline testing versus somatic testing. For germline testing in ovarian cancer, it is recommended by multiple different societies that all women with non-mesothelial ovarian cancer should undergo germline testing because there is a high rate of BRCA pathogenic variants.

That's really important because it can inform cascade testing—or testing for family members to identify who may be at risk developing both breast and ovarian cancers, as well as some other cancers, like pancreatic cancer or prostate cancer. It's important for patients with ovarian cancer and their family members to know [about BRCA pathogenic variants] because it may lead to the ability to obtain targeted therapies like PARP inhibitors.

Beyond germline testing, you can also test the tumor [through somatic testing]. By testing the tumor, you can expand who may be eligible for receiving PARP inhibitors and also give you an idea if there's potentially other targeted therapies that you could provide for these women. It's important to understand the difference between these [tests] because we do have insurance approval for germline testing as long as the testing goes in with a letter of medical necessity; however, somatic testing is not always approved. Therefore, you have to make sure you know the test that you're ordering. Often, the somatic tests have an expanded panel and you want to know that the tests you are ordering are going to help the patients.

With homologous recombination deficiency testing, we're hoping this will help inform us which patient may be eligible for certain types of therapies in the future. However, at this point, we don't have one single test for this. Therefore, it's used mostly in the trial setting to help try and find patients who may benefit from therapeutic interventions, such as PARP inhibitors.

In liquid biopsies, you're looking at cell-free DNA for various components of tumor cells that can be sampled within the blood. [Liquid biopsies] are not ready for prime time, but we're hopeful that this might turn into a less invasive way to help us with diagnosis screening and therapeutic interventions in the future. It is so important to have genetic counselors involved in the care of these women because test results need to be interpreted by people who know what they're looking at. And, they can provide women with comprehensive information about options for themselves and family members.

What research has supported the use of molecular testing?

When we look at other cancers in which we specifically do germline testing, the rate of cancer development for patients who harbor a germline mutation guide who should undergo this genetic testing. A good example is Lynch syndrome. These patients have a 40% to 60% risk of developing endometrial cancer if there is a family history. [Family history] is an important component to take into consideration, which is why the guidelines recommend all patients with ovarian cancer to undergo testing. About 15% to 20% of women are going to develop ovarian cancer.

From a somatic standpoint, it is important to look at new ways to treat these patients. We have been pretty stagnant in the way we treat them. Understanding the molecular landscape for these cancers is very important in trying to move the field forward. It is important to do the work in the lab in a controlled setting, but we also need to understand what's happening in patients on a day-to-day basis.

What are the biggest remaining challenges with molecular testing?

The biggest challenge is making sure that you don't end up with a bill for the patient. We can get the germline testing approved a vast majority of the time for patients with ovarian cancer. Right now, I advocate doing that across the board because I know we can get the approval from insurance; I know that testing can be done and that's important information. I would love to see patients getting both somatic and germline testing so we can expand on knowledge on the molecular profile, not only in germline but what's happening in the tumor, to allow us to be more open to what we can provide for these women.

What are your thoughts on utilizing liquid biopsies in this space?

That is moving forward more rapidly in cancers that are more common. Therefore, we have the ability to test and see [mutations] more frequently in diseases such as breast cancer or colon cancer, but it's still often in the experimental phase of things. Most of these companies that provide next-generation sequencing platforms that are used for somatic testing are expanding into liquid biopsies with the understanding that while they can do testing on a tumor that is from surgery, sometimes that tissue is not available. Sometimes, you can't send them for biopsy. Sometimes, you have insufficient tissue when you do biopsy.

Additionally, people are used to blood draws; they are comfortable with them. They can have them done through their ports, and it's much less invasive. As the technology progresses, everybody is looking for a test that is easier on the patient because our primary goal is to treat them with minimal amount of trauma or adverse events.

What else should be known about genetic counseling?

As providers, we need to know what we're ordering. While we're trying to understand the biology of the cancer and even understand genetics, our training is not the same as a genetic counselor. We also often have limited time. We don't have an hour to sit down and diagram the family history, understand where everyone comes into play, and have a big discussion about mutations and what patients and their families need to know. They are a huge, valuable resource because they have all of that information and they stay up to date on it. If we want our patients to be armed with information, then having [genetic counselors] be a part of this is crucial.