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Molecular Testing in Ovarian Cancer

Panelists: Bradley J. Monk, MD, FACS, FACOG, Arizona Oncology Practice of US Oncology; Oliver Dorigo, MD, PhD, Stanford University Medical Center; Thomas Herzog, MD, University of Cincinnati Cancer Institute; Kathleen Moore, MD, Stephenson Cancer Center; Leslie M. Randall, MD, MAS, University of California, Irvine
Published: Friday, Aug 10, 2018



Transcript: 

Bradley J. Monk, MD, FACS, FACOG: Let’s talk about genetic testing. The NCCN, the American Society of Clinical Oncology, and the Society of Gynecologic Oncology recommend that all people with epithelial ovarian cancer be tested for germline BRCA mutations. Would we agree with that?

Kathleen Moore, MD: Absolutely.

Leslie M. Randall, MD, MAS: Absolutely.

Oliver Dorigo, MD, PhD: I think, Brad, we all do this and follow the guidelines.

Bradley J. Monk, MD, FACS, FACOG: I love it. Thank you. So, who should counsel those patients? I think you’d also agree that those patients need genetic counseling. Katie, do you refer those patients to genetic counseling, or would your nurse practitioner or you counsel the patient?

Kathleen Moore, MD: In our practice, we do have genetic counselors available, but there aren’t enough. And so, I counsel the patients myself for genetic testing. We’ll talk, I think, a little bit more about the type of testing one would send, but I counsel them. If we have a positive result, or if we have sort of a noninformative result in a patient whose family history is striking, these are patients who I’m going to prioritize getting into seeing genetic counselors because you just can’t send every single patient. There are not enough genetic counselors. I think the best practice is to send every patient who needs testing to a genetic counselor—100%. They do a better job, but there just are not enough of them. So, I counsel on my own.

Bradley J. Monk, MD, FACS, FACOG: I see everyone nodding their heads, so I’m not going to discuss that further. I think that’s fairly common. In my practice, my nurse practitioners really enjoy that, and they’ve taken that as their passion. As you said, Leslie, it’s the cure for ovarian cancer. It’s the Angelina Jolie effect—identifying patients at risk and stopping it within the kindred by doing a risk-reducing surgery. Are there other reasons to test for BRCA, other than for risk-reducing surgery? And if there are, what are they?

Leslie M. Randall, MD, MAS: Prognosis. They have a different prognosis.

Bradley J. Monk, MD, FACS, FACOG: Tell me more. What kind of prognosis? Better or worse?

Leslie M. Randall, MD, MAS: In general, they have a better prognosis than those who don’t have germ line mutations. It’s not always the case. Also, to triage them to clinical trials. In the frontline setting, it may be that we start to triage them to treatment based on their germline BRCA status.

Bradley J. Monk, MD, FACS, FACOG: Interesting.

Leslie M. Randall, MD, MAS: It’s not currently the situation, but that’s evolving.

Bradley J. Monk, MD, FACS, FACOG: Oliver, is it just BRCA, or do they need testing for what we call panel testing, meaning other genes that may be associated with ovarian cancer?

Oliver Dorigo, MD, PhD: Yes, absolutely. A panel of genes that increase a woman’s risk to develop ovarian cancer during her lifetime is constantly increasing. The genetic mutations we are identifying are responsible for a lesser and lesser percentage of those ovarian cancer cases.

Bradley J. Monk, MD, FACS, FACOG: Excellent point.

Oliver Dorigo, MD, PhD: Nevertheless, it’s very important to do these panels. As a matter of fact, I was curious about what you guys do because a woman who comes to my clinic had a germ line mutation 5 years ago. She had a very different, smaller panel from what is available at this point.

Bradley J. Monk, MD, FACS, FACOG: Yes. In my practice, we have kind of created a threshold of 3 years, but that’s unstable. When do you retest, Leslie? When does someone show up and say, “I’ve been BRCA tested.” Or maybe she has even had a panel test.” When is that no longer valid because the science has moved on?

Leslie M. Randall, MD, MAS: I don’t have the answer to that question. Patients ask me, and it’s hard.

Bradley J. Monk, MD, FACS, FACOG: We say about 2015. What do you think?

Thomas Herzog, MD: For just BRCA?

Bradley J. Monk, MD, FACS, FACOG: Let’s say they had the panel at the time.

Thomas Herzog, MD: I don’t know. I was going to guess 5 years or so.

Kathleen Moore, MD: I don’t know that there’s a set time. I think the companies that are doing the genetic testing have been pretty informative when the panels change. And so, it’s not a common occurrence, but we have patients who… I’m taking care of a woman whose mother unfortunately died of ovarian cancer in our practice 10 years ago. She was tested and was negative. She is definitely getting tested, because she needs it, but also because she was tested at the time her mom tested negative. She’s getting retested now because the panel is completely different.

Bradley J. Monk, MD, FACS, FACOG: Yes. The BRCA testing is different.

Kathleen Moore, MD: And the panel is different. There wasn’t a panel yet. The genes, or the mutations that you test for have changed. Under those circumstances, that might be another patient who I would send to the genetic counselor, to sort of guide whether we should retest.

Leslie M. Randall, MD, MAS: It sounds like a risk-based approach, which I think makes a lot of sense.

Kathleen Moore, MD: Yes.

Bradley J. Monk, MD, FACS, FACOG: So, we all agree that every patient with ovarian, fallopian tube, and tubal cancer should be tested for the germline BRCA mutation and, ideally, for a panel. That counseling is mandatory, and who does the counseling is open to your practice pattern. BRCA can also happen in the tumor but not in the germline. That’s obviously called a somatic mutation. What is the role of somatic BRCA testing in your practice, Katie?

Kathleen Moore, MD: Currently, in our practice, outside of clinical trials, we’re testing ovarian cancer patients at the time of a recurrence for somatic mutations. Depending on the length of time from their primary surgery, we typically rebiopsy them. Maybe we don’t need to be doing that. You are going to have patients who are cured, and you don’t ever need to know that information. So, we wait. And again, the panels change, so we want to get the most up-to-date panel when we need the information.

Bradley J. Monk, MD, FACS, FACOG: And the tumor may evolve, right? The heterogeneity.

Kathleen Moore, MD: The tumor may evolve. How much that happens—I think current studies are investigating that. This is really going to inform the necessity of a repeat biopsy in ovarian cancer. We don’t know right now.

Bradley J. Monk, MD, FACS, FACOG: Tom, do you test for somatic upfront?

Thomas Herzog, MD: We do. We send a panel, so we get that information.

Bradley J. Monk, MD, FACS, FACOG: Interesting. Katie says, “Oh, I’m going to rebiopsy the tumor because the tumor may change.” We’re all familiar with the cell-free DNA technology. Is that an opportunity? You have chronologic heterogeneity, but you have spatial heterogeneity. And if you do the cell-free DNA, or circulating tumor cell but cell-free DNA, it’s the entire tumor that has been interrogated. What do you think?

Oliver Dorigo, MD, PhD: Maybe.

Bradley J. Monk, MD, FACS, FACOG: You’re the expert. Don’t tell me maybe.

Oliver Dorigo, MD, PhD: It’s a beautiful theory, but we don’t know this. We have evolving data from a beautiful paper out of Vancouver, from March 2018, that looked at the intrapatient heterogeneity of ovarian cancer on the metastatic side. That paper, in 38 patients with 250 biopsies, really brought home the point that these sites are very different when it comes to the immunological and genomic profiles. We still have to do correlative studies on how cell-free DNA is representative of at least most of the tumor site inside the patient. That’s my opinion.

Bradley J. Monk, MD, FACS, FACOG: The other role, Leslie, for cell-free DNA is prognosis. We live in a CA-125 world. In patients who are treated, we monitor them with physical exams, symptoms, and CA-125. Some people say, “I want to see if the cell-free DNA comes back.” Does that make any sense? Is it not added value in more carefully monitoring the patient for recurrence?

Leslie M. Randall, MD, MAS: That has been shown to be of value in prostate… Actually, it has been shown to be better.

Bradley J. Monk, MD, FACS, FACOG: But in ovarian cancer, can you do it?

Leslie M. Randall, MD, MAS: We have not looked at that yet.

Bradley J. Monk, MD, FACS, FACOG: OK.

Transcript Edited for Clarity 

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Transcript: 

Bradley J. Monk, MD, FACS, FACOG: Let’s talk about genetic testing. The NCCN, the American Society of Clinical Oncology, and the Society of Gynecologic Oncology recommend that all people with epithelial ovarian cancer be tested for germline BRCA mutations. Would we agree with that?

Kathleen Moore, MD: Absolutely.

Leslie M. Randall, MD, MAS: Absolutely.

Oliver Dorigo, MD, PhD: I think, Brad, we all do this and follow the guidelines.

Bradley J. Monk, MD, FACS, FACOG: I love it. Thank you. So, who should counsel those patients? I think you’d also agree that those patients need genetic counseling. Katie, do you refer those patients to genetic counseling, or would your nurse practitioner or you counsel the patient?

Kathleen Moore, MD: In our practice, we do have genetic counselors available, but there aren’t enough. And so, I counsel the patients myself for genetic testing. We’ll talk, I think, a little bit more about the type of testing one would send, but I counsel them. If we have a positive result, or if we have sort of a noninformative result in a patient whose family history is striking, these are patients who I’m going to prioritize getting into seeing genetic counselors because you just can’t send every single patient. There are not enough genetic counselors. I think the best practice is to send every patient who needs testing to a genetic counselor—100%. They do a better job, but there just are not enough of them. So, I counsel on my own.

Bradley J. Monk, MD, FACS, FACOG: I see everyone nodding their heads, so I’m not going to discuss that further. I think that’s fairly common. In my practice, my nurse practitioners really enjoy that, and they’ve taken that as their passion. As you said, Leslie, it’s the cure for ovarian cancer. It’s the Angelina Jolie effect—identifying patients at risk and stopping it within the kindred by doing a risk-reducing surgery. Are there other reasons to test for BRCA, other than for risk-reducing surgery? And if there are, what are they?

Leslie M. Randall, MD, MAS: Prognosis. They have a different prognosis.

Bradley J. Monk, MD, FACS, FACOG: Tell me more. What kind of prognosis? Better or worse?

Leslie M. Randall, MD, MAS: In general, they have a better prognosis than those who don’t have germ line mutations. It’s not always the case. Also, to triage them to clinical trials. In the frontline setting, it may be that we start to triage them to treatment based on their germline BRCA status.

Bradley J. Monk, MD, FACS, FACOG: Interesting.

Leslie M. Randall, MD, MAS: It’s not currently the situation, but that’s evolving.

Bradley J. Monk, MD, FACS, FACOG: Oliver, is it just BRCA, or do they need testing for what we call panel testing, meaning other genes that may be associated with ovarian cancer?

Oliver Dorigo, MD, PhD: Yes, absolutely. A panel of genes that increase a woman’s risk to develop ovarian cancer during her lifetime is constantly increasing. The genetic mutations we are identifying are responsible for a lesser and lesser percentage of those ovarian cancer cases.

Bradley J. Monk, MD, FACS, FACOG: Excellent point.

Oliver Dorigo, MD, PhD: Nevertheless, it’s very important to do these panels. As a matter of fact, I was curious about what you guys do because a woman who comes to my clinic had a germ line mutation 5 years ago. She had a very different, smaller panel from what is available at this point.

Bradley J. Monk, MD, FACS, FACOG: Yes. In my practice, we have kind of created a threshold of 3 years, but that’s unstable. When do you retest, Leslie? When does someone show up and say, “I’ve been BRCA tested.” Or maybe she has even had a panel test.” When is that no longer valid because the science has moved on?

Leslie M. Randall, MD, MAS: I don’t have the answer to that question. Patients ask me, and it’s hard.

Bradley J. Monk, MD, FACS, FACOG: We say about 2015. What do you think?

Thomas Herzog, MD: For just BRCA?

Bradley J. Monk, MD, FACS, FACOG: Let’s say they had the panel at the time.

Thomas Herzog, MD: I don’t know. I was going to guess 5 years or so.

Kathleen Moore, MD: I don’t know that there’s a set time. I think the companies that are doing the genetic testing have been pretty informative when the panels change. And so, it’s not a common occurrence, but we have patients who… I’m taking care of a woman whose mother unfortunately died of ovarian cancer in our practice 10 years ago. She was tested and was negative. She is definitely getting tested, because she needs it, but also because she was tested at the time her mom tested negative. She’s getting retested now because the panel is completely different.

Bradley J. Monk, MD, FACS, FACOG: Yes. The BRCA testing is different.

Kathleen Moore, MD: And the panel is different. There wasn’t a panel yet. The genes, or the mutations that you test for have changed. Under those circumstances, that might be another patient who I would send to the genetic counselor, to sort of guide whether we should retest.

Leslie M. Randall, MD, MAS: It sounds like a risk-based approach, which I think makes a lot of sense.

Kathleen Moore, MD: Yes.

Bradley J. Monk, MD, FACS, FACOG: So, we all agree that every patient with ovarian, fallopian tube, and tubal cancer should be tested for the germline BRCA mutation and, ideally, for a panel. That counseling is mandatory, and who does the counseling is open to your practice pattern. BRCA can also happen in the tumor but not in the germline. That’s obviously called a somatic mutation. What is the role of somatic BRCA testing in your practice, Katie?

Kathleen Moore, MD: Currently, in our practice, outside of clinical trials, we’re testing ovarian cancer patients at the time of a recurrence for somatic mutations. Depending on the length of time from their primary surgery, we typically rebiopsy them. Maybe we don’t need to be doing that. You are going to have patients who are cured, and you don’t ever need to know that information. So, we wait. And again, the panels change, so we want to get the most up-to-date panel when we need the information.

Bradley J. Monk, MD, FACS, FACOG: And the tumor may evolve, right? The heterogeneity.

Kathleen Moore, MD: The tumor may evolve. How much that happens—I think current studies are investigating that. This is really going to inform the necessity of a repeat biopsy in ovarian cancer. We don’t know right now.

Bradley J. Monk, MD, FACS, FACOG: Tom, do you test for somatic upfront?

Thomas Herzog, MD: We do. We send a panel, so we get that information.

Bradley J. Monk, MD, FACS, FACOG: Interesting. Katie says, “Oh, I’m going to rebiopsy the tumor because the tumor may change.” We’re all familiar with the cell-free DNA technology. Is that an opportunity? You have chronologic heterogeneity, but you have spatial heterogeneity. And if you do the cell-free DNA, or circulating tumor cell but cell-free DNA, it’s the entire tumor that has been interrogated. What do you think?

Oliver Dorigo, MD, PhD: Maybe.

Bradley J. Monk, MD, FACS, FACOG: You’re the expert. Don’t tell me maybe.

Oliver Dorigo, MD, PhD: It’s a beautiful theory, but we don’t know this. We have evolving data from a beautiful paper out of Vancouver, from March 2018, that looked at the intrapatient heterogeneity of ovarian cancer on the metastatic side. That paper, in 38 patients with 250 biopsies, really brought home the point that these sites are very different when it comes to the immunological and genomic profiles. We still have to do correlative studies on how cell-free DNA is representative of at least most of the tumor site inside the patient. That’s my opinion.

Bradley J. Monk, MD, FACS, FACOG: The other role, Leslie, for cell-free DNA is prognosis. We live in a CA-125 world. In patients who are treated, we monitor them with physical exams, symptoms, and CA-125. Some people say, “I want to see if the cell-free DNA comes back.” Does that make any sense? Is it not added value in more carefully monitoring the patient for recurrence?

Leslie M. Randall, MD, MAS: That has been shown to be of value in prostate… Actually, it has been shown to be better.

Bradley J. Monk, MD, FACS, FACOG: But in ovarian cancer, can you do it?

Leslie M. Randall, MD, MAS: We have not looked at that yet.

Bradley J. Monk, MD, FACS, FACOG: OK.

Transcript Edited for Clarity 
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