Essential Genetic Testing for Personalized Gynecologic Cancer Treatment
How important is genetic testing for gynecologic cancer? Expert Dr. Ramez Eskander from UC San Diego Health discusses the role of genetic testing in gynecologic cancer care – including molecular tumor testing, germline testing, HRD tests, and BRCA mutations – along with proactive patient advice.
[ACT]IVATION TIP
“…every patient with ovarian cancer needs to know their BRCA status and needs to know their molecular tumor testing status. Feel empowered to ask these questions. It is data that you should have at hand as you make informed decisions.”
See More from [ACT]IVATED Ovarian Cancer
Related Resources:
Optimizing Ovarian Cancer Care: Genetic Testing and Treatment Approaches |
PARP Inhibitors in Ovarian Cancer Treatment: Understanding Side Effects |
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Transcript:
Lisa Hatfield:
Dr. Eskander, for patients newly diagnosed with a gynecologic cancer, how important is it to get genetic testing like HRD or homologous recombination deficiency, and how can understanding one’s genetic profile help them and their care team choose the best treatment?
Dr. Ramez Eskander:
This is an incredibly important question. It is pivotal that every newly diagnosed ovarian cancer patient have germline genetic testing and molecular tumor testing because of the impact it can have on their treatment strategy, independent of course, the importance of them being diagnosed. So that if they had a genetically inherited mutation, we call it germline mutation, their relatives can be informed and tested, so they can have risk reducing surgical interventions.
In the ovarian cancer setting, homologous recombination deficiency testing is crucial, because it helps inform the magnitude of benefit that we might see with treatment strategy, in this case, combination of PARP inhibitor plus bevacizumab (Avastin) or PARP inhibitor alone. So these treatment strategies have been proven to improve clinical outcomes. And knowing HRD test status and knowing whether you have a germline mutation is pivotal to putting context around a conversation surrounding maintenance treatment approaches. And understanding the profile is what drives your ability to make an informed decision about your maintenance treatment strategies.
And it can be quite nuanced. For example, if a patient is HRD test-negative, they would have to make a decision about what kind of maintenance therapy with their provider. Do I do maintenance treatment? Should I do bevacizumab alone? Should I do a PARP inhibitor alone? And what might I anticipate with either of these approaches, and what are the pros and the cons? And an HRD test-positive patient, there is clear data supporting the use of PARP inhibitors or PARP inhibitors plus bevacizumab in combination.
So you want to be informed of those data as you look to make a decision. And this to me is germane to the care of patients with ovarian cancer. Every patient should know their status and in a similar manner when we talk about endometrial cancer, I would just like to elaborate that it’s critical to know what is the finding of the testing on the tumor for the endometrial cancer? Is this a mismatch repair-deficient or mismatch repair-proficient endometrial cancer and testing that was done?
Lisa Hatfield:
That’s a lot of information. So I just want to clarify a couple of comments that you made. So when you talk about the germline testing of germline mutations, that has to do with mutations that are present in a patient’s, all the cells in a patient’s body. Is that correct? So like the BRCA1 and 2 genes?
Dr. Ramez Eskander:
That’s correct.
Lisa Hatfield:
And then there are the other types of mutations, some people call them somatic mutations that are just have to do with the DNA sequencing of the actual tumor or cancer cells. So is HRD then, is that a germline mutation, or is that more of a somatic?
Dr. Ramez Eskander:
Perfect question. So HRD itself isn’t a mutation. HRD is looking at changes in the tumor DNA, but you bring up a perfect point. A germline mutation is inherited, meaning that it is in every cell, and it’s a predisposition and increase in cancer risk. Somatic mutations are not inherited. Somatic mutations are mutations in the tumor unique to that cancer. That’s why we talk about informing your family or relatives with a germline mutation, because that was inherited. And other people in the family may have the same inherited mutation. Somatic mutations are not inherited. They arise in the cancer, and they require tumor testing to inform.
Homologous recombination deficiency isn’t looking for a specific mutation, but it’s rather examining the tumor DNA to look for something we call genomic scarring. The analogy I gave is if I’m driving on the freeway and I’m stuck in traffic, I know that I’m stuck in traffic, but I don’t know exactly why. Is there construction on the freeway? Is there an accident? It’s unclear. So the HRD is looking at the genomic signature, and it needs tumor samples to do that, but it’s not honing in on a specific mutation.
I know it can get a little bit complicated. I’ll just add this, A patient who has a germline BRCA mutation, if you test their tumor, the near vast majority are going to have an HRD test-positive signature, because it drives that. So that’s like saying, I know the reason that there’s that genomic instability, it’s a BRCA mutation, but there are patients we call beyond BRCA. There are many things that may cause this independent of BRCA that we may not know of right now, but we can identify the genomic scar, and that qualifies patients as having a homologous recombination deficiency test-positive tumor.
So my tip is every patient with ovarian cancer needs to know their BRCA status and needs to know their molecular tumor testing status. Feel empowered to ask these questions. It is data that you should have at hand as you make informed decisions.
