The Latest in Genetic Testing and Screening among Gynecologic Cancer Patients
Genetic testing and screening in gynecologic cancer patients has evolved over the last several years. Miriam AlHilli, MD joins the Cancer Advances podcast to discuss the latest in genetic testing, screening and prevention.
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The Latest in Genetic Testing and Screening among Gynecologic Cancer Patients
Podcast Transcript
Dale Shepard, MD, PhD: Cancer Advances, a Cleveland Clinic podcast for medical professionals, exploring the latest, innovative research and clinical advances in the field of oncology. Thank you for joining us for another episode of Cancer Advances. I'm your host, Dr. Dale Shepard, a medical oncologist here at Cleveland Clinic overseeing our Taussig Phase I and Sarcoma programs. Today, I'm happy to be joined by Dr. Mariam AlHilli, a gynecologic oncologist at Cleveland Clinics' Women's Health Institute. So welcome, Miriam.
Mariam AlHilli, MD: Thank you.
Dale Shepard, MD, PhD: So maybe just give us just a little background on what your role is here at Cleveland Clinic.
Mariam AlHilli, MD: I'm a gynecologic oncologist. I see women with various gynecologic malignancies, and we evaluate patients for surgery, and then they follow up with us in our clinic for their postoperative care, typically chemotherapy. We work closely with our multidisciplinary team, with our radiation oncologists. We also have a focus on high risk women with genetic conditions as well that we see in our clinic on a regular basis.
Dale Shepard, MD, PhD: Great. So maybe you could start by telling us a little bit about genetic testing in women with ovarian cancer.
Mariam AlHilli, MD: The concept of genetic testing, just like with all other cancers, has really evolved over the last several years. And at this time, all women with a diagnosis of ovarian cancer including all histologies, with the exception of probably mucinous carcinomas of the ovary and the epithelial types of ovarian cancers. All of these women are recommended to undergo genetic testing following their diagnosis. That is based on data showing that the incidents of these women not only having BRCA or BRCA 1 or 2 gene mutations, but genes that are in the same pathway and related genes can be up to 20%.
So one in five women can have a genetic mutation, which would influence the prognosis treatment and their disease course. So that's our current recommendation.
Dale Shepard, MD, PhD: And so this is testing in patients who have been identified as having ovarian cancer?
Mariam AlHilli, MD: Correct. This is in women that have ovarian cancer. The criteria are very different in women who are suspected to have a genetic mutation based on family history.
Dale Shepard, MD, PhD: So maybe you could tell us a little bit about that. Who should we be sending for testing?
Mariam AlHilli, MD: The NCCN probably has the most comprehensive list of what these indications are for genetic testing. But for women who are suspected to have a family history of ovarian cancer, all these women should be referred to genetic counseling. Particularly if a women has a first degree relative with ovarian cancer, the incidents of ovarian cancer in this situation is significantly higher. We recommend that these women be seen by a genetic counselor and assessed, and then they would typically undergo a panel testing, a multi-gene panel testing. Having a first degree relative, even a second degree relative, can increase risk.
And that risk is about 3% for a second degree relative and having two relatives or more with ovarian cancer as well.
Dale Shepard, MD, PhD: When we think about having the genetic counseling and assessing risk and you mentioned 3% risk, where does that go from there? Typically, everyone's concerned of the fact that ovarian cancer, for instance, oftentimes is identified very late and about screening the general population versus these people who are more susceptible. How does that impact any screening procedures, or what do we do with that increased risk? How do we use that in a clinical way?
Mariam AlHilli, MD: Clinically, first, after a woman undergoes genetic testing and is confirmed to have a genetic mutation, there's the BRCA 1 and BRCA 2 genes, which are the high penetrance genes, and those would increase women's risk for BRCA 1 of developing ovarian cancer over a lifetime of about 40 to 45%, and for BRCA 2 about 15 to 20%. There are also other genes that are related to BRCA 1 and BRCA 2 that have lower penetrance. Overall risk of somewhere between five to 15% over their lifetime. In women that are confirmed to be high risk, we enroll them in a screening program where they are seen by a gynecologic oncologist and they would undergo ultrasound screening. Depending on their age, ultrasound and CA 125.
If they haven't completed their family and they're still interested in fertility, typically every six months. And for women that have completed their family and are not interested in future fertility, then we would recommend a risk reducing surgery as the most definitive option for risk reduction. And that's also age dependent and mutation dependent. So typically for BRCA 1 gene carriers, the recommended age of considering a risk reducing surgery is between 35 to 40 and between 40 to 45 for BRCA 2 mutation carriers, because they do develop ovarian cancer approximately 10 years later.
Dale Shepard, MD, PhD: So really the screening of these high risk women can significantly decrease the likelihood that you end up with late stage disease, which is great. What other things are we screening for in women with a potential for gynecologic cancers?
Mariam AlHilli, MD: As you know, the screening tests for ovarian cancer are in the general population not sensitive or specific. But in high risk women, they may lead to detection at an earlier stage. With women that have a diagnosis of endometrial cancer, what we do in our practice and a lot of other practices nationally and internationally is we do somatic testing. So tumors are tested with immunohistochemistry for mismatch repair proteins, and that can then guide further genetic testing and referral to a genetic counselor. So women with endometrial cancer, about 5% of endometrial cancers can be inherited as part of Lynch syndrome.
And women that have a diagnosis of Lynch syndrome are at significantly higher risk than the general population of endometrial cancer and their bus can be between 40 to 60%. So the screening in these women is a little different apart. From endometrial cancer, they're also at risk for ovarian cancer, about 10 to 15% risk of that. So it's lower, but it's significant. And they're screened with an endometrial biopsy. There's controversy, but we in our practice recommend doing an endometrial biopsy annually in addition to an ultrasound and CA 125 to evaluate the ovaries.
Dale Shepard, MD, PhD: Now, the screening you've mentioned and the testing you mentioned is something that we're certainly set up and equipped to do, but is this something that happens as commonly in the community or in other centers? Or how about access to this for most patients?
Mariam AlHilli, MD: Yeah, so we're very fortunate here because we have an excellent multidisciplinary center working with women with Lynch syndrome. They get enrolled in a Lynch syndrome registry, and they receive comprehensive screening. In the community, we highly recommend that these women see a genetic counselor. And once they're diagnosed, be either referred to our center or that the physicians would use the resources available to follow guidelines to perform appropriate screening for these women based on the guidelines.
Dale Shepard, MD, PhD: Do we have very many patients who will come in sort of as consult specifically for screening?
Mariam AlHilli, MD: We actually do. We also have a large referral center for high risk women with breast and ovarian cancer. And I see women in my practice with the diagnosis of Lynch syndrome who come in as part of the Y center. The colorectal GI screening program is very efficient, and these women come in from different states. They come in and get all of their screening tests done on the same day, and then their screening is satisfied.
Dale Shepard, MD, PhD: Is that something we have also been able to push out to our regional sites, or is that something that's primarily main campus? What does that look like?
Mariam AlHilli, MD: So although the patients typically can have all of their screening tests done by physicians that are at the main campus, there definitely are resources to have appropriate screening tests done in the region. And once they're connected with the multidisciplinary center, then a patient can choose to have their screening tests done anywhere in the region as long as they're connected to the system.
Dale Shepard, MD, PhD: So I guess thinking about not only gynecologic cancers, but cancers that we do screening in general, getting people to actually get the screening tests is always a problem. How effectively do you think that we're identifying people at risk and then making that next step to actually get them screened? What do you think about our ability to catch the right patients and make the right things happen and how do we make that better if it's not ideal?
Mariam AlHilli, MD: Right. That's a very a good question. Again, here being a big referral center, we end up seeing a lot of patients that are high risk and end up enrolling in screening programs. But as the data shows, we definitely are not capturing all patients, and there are definitely barriers to patient's ability to get into the system and be screened or even tested. And there are a lot of social barriers that come to mind in terms of this. But the main thing is increasing awareness, encouraging women or men as well that have a family history to encourage the relative that has the diagnosis to undergo a genetic testing, if they qualify for genetic testing.
And once a family member is identified, then cascade testing can be done so other family members would be subsequently tested. So I think awareness is the most important thing. Screening at the level of primary care is also helpful and that is a definite access point that can be targeted.
Dale Shepard, MD, PhD: Do we have any educational sort of outreach efforts going on either directly to patients or to physicians that that might help this? Because, I mean, clearly screening helps and screening works, it's just a shame to have it not be utilized. Do we have any of those efforts?
Mariam AlHilli, MD: We have over the years had our panel discussions that patients are invited to, and we've had outreach programs to our community. But that's definitely an area that can be enhanced. At this point in time, there definitely are system issues with the current situation barriers to that. But we want to be able to get out to the community and increase awareness. There have been efforts over the years.
Dale Shepard, MD, PhD: You just mentioned recent barriers, and I guess that was my next question, how certainly other cancers, breast cancer and colon cancer and things, have been impacted by the COVID pandemic. How has the screening been impacted and how are we trying to avoid problems in the future by decreased screening if that's happening?
Mariam AlHilli, MD: So the patients that are currently in our screening program and our established, we have still been offering them appointments. Virtual visits are great for patients who are not necessarily in need of coming in to be examined, but can have their counseling done virtually on the phone. So we have those resources available, but we... Just like other specialties in cancers, there has been a decline in our number of consults in general. And I think it's important for physicians in the community for patients to be aware that if they feel that they're at risk or high risk that our physicians and our genetic counselors can reach out to them virtually for consultation and make the testing process easier.
And we've done an excellent job here at the clinic in protecting patients and family members and physicians alike.
Dale Shepard, MD, PhD: So certainly a lot of this, you said, had been based on what we know about risk and selecting patients based on like BRCA 1, BRCA 2. Anything that looks promising or anything being worked on, either in the basic science or the clinical arena, that looks like another marker that might help guide any of these gynecologic tumors and screening efforts?
Mariam AlHilli, MD: Definitely. This is a very hot area in gynecologic oncology right now. There had been targeted therapies that are being introduced. So PARP inhibitors namely. They've now been incorporated and FDA approved and part of our care. And that's based on the fact that women with ovarian cancer, are, like I said previously, one in five women could have a genetic diagnosis of one BRCA 2 as well as other related genetic defects. But then there's the concept of a homologous recombination deficiency. So that's where tumors characteristically genotypically are considered either to have genomic instability or genetic mutations in the pathway of BRCA, the homologous recombination DNA repair pathway.
So this is a test that is offered to patients who test negative for BRCA 1 and BRCA 2, and it can increase the detection rate of homologous recombination deficient tumors. And those patients would qualify for treatment with targeted therapy, particularly PARP inhibitor.
Dale Shepard, MD, PhD: When we think about who comes in for screening, it's certainly awareness and identification of people at risk is important. What kind of issues do you deal with in terms of coverage for either the genetic screening, the genetic counseling or the testing, and how big of a factor is that?
Mariam AlHilli, MD: Definitely that does come up during consultations. What I would typically tell patients is that seeing the genetic counselor is the first step. And most insurance companies do a really good job of approving patients for screening and for risk reducing surgery. So it's not a common barrier that we encounter, but every now and then there are issues that are raised in terms of insurance. And I think that is also evolving with time as there's more information and data available on how these patients do and the reduction in mortality that these patients get through screening and through risk reducing surgeries.
Dale Shepard, MD, PhD: Well, Mariam, you had some great insights for us today. Any additional comments?
Mariam AlHilli, MD: Thank you for having me on this podcast. And I think it's very important to raise awareness on screening, genetic screening and testing. And that we hope to be able to help physicians in the community by having our resources readily available, that they don't have to think about or counsel patients any differently by just a simple phone call or referral. We can get them in and get them enrolled in our program.
Dale Shepard, MD, PhD: Well, thank you very much.
Mariam AlHilli, MD: Thank you.
Dale Shepard, MD, PhD: This concludes this episode of Cancer Advances. You will find additional podcast episodes on our website, clevelandclinic.org/canceradvancespodcast. Subscribe to the podcast on iTunes, Google Play, Spotify, SoundCloud, or wherever you listen to podcasts. And don't forget, you can access real-time updates from Cleveland Clinics' cancer center experts on our Consult QD website at consultqd.clevelandclinic.org/cancer. Thank you for listening. Please join us again soon.