Scott Webb (Host): Today, we're discussing genetic testing to determine a patient's risk for cancer, including the step-by-step process of genetic testing with Dr. Umangi Patel. She's the Medical Director of MSLC Oncology Services. This is Doc Talk, presented by Montefiore St. Luke's Cornwall. I'm Scott Webb.

Doctor, it's nice to have you here today. We're going to talk about genetic testing for cancer risk and what does that mean, of course. So, let's start there. Who should seriously consider genetic testing for cancer risk and what specific personal or family red flags should prompt a referral to genetic counseling?

Dr. Umangi Patel: So, any patient who has personal history of triple-negative breast cancer, personal history of ovarian cancer, pancreatic cancer, cancer of the colon that is diagnosed before age 50, any male breast cancer at any age, metastatic cancer of the prostate, multiple different types of cancer in one individual patient, cancer history in the family with cancer of the colon and uterus both, or patient having cancer in both organs such as both breasts, both kidneys, et cetera. Those are all patients would be a red flag for us clinicians as well as for patient that they should have genetic counseling and testing. So, this should prompt genetic testing.

Host: Right. Yeah. So, you give us a sense there some of the red flags, who's at the highest risk. So then, doctor, take us through the typical step-by-step process of genetic testing for cancer risk from, let's say, the first consultation with a genetic counselor through some sample collection, insurance authorization, getting results. You know, take us through that process.

Dr. Umangi Patel: So generally, when a patient is going to a primary care physician or maybe a specialist for a variety of reasons, and the family history as well as personal history is obtained by the particular clinician. And then, a genetic test indication is being discussed that your history tells us that you may be harboring a genetic mutation or you may not. But in order for us to know, we should do a test, and the test can be either blood test or saliva test.

And in terms of getting insurance authorization, primarily, most of the insurance companies this day and age definitely approve this based on what history is submitted. And once the authorization is obtained, the blood is processed by the genetic companies, you know, whether it is Myriad, whether it is Invitae genetic testing that are doing this multi-gene panel. And then, the results gets reported to the physician who ordered it. And then, in someone like me, who is in practice in oncology, while would review the results with the patient and explain to them the implications of these, I still make sure that they are referred to a genetic counselor to understand further for personal risk of other family members.

Host: Right. Yeah, I wanted to talk to you about single gene tests and how they might differ from multi-gene panels and which clinical situations maybe is each type, let's say, preferred.

Dr. Umangi Patel: In the past, when we kind of had limited understanding of genetics and also number of genes that have been, you know, identified over the period of past couple of decades, a single gene mutation, we kind of try not to do it, because people even if there is a breast cancer history and/or ovarian cancer history and patient would say, "Well, I know I need to do BRCA testing," because that is kind of out there in general public's information, understanding, knowledge, et cetera.

However, there are many other genes that could also lead to breast cancer or could lead to other cancers, and not necessarily only BRCA gene. So by and large, we prefer not to do single gene mutation and do multi-gene panel. Having said that, let's say if patient walks into your office and says, "My sister was diagnosed to have this, that, and the other cancer, and her genetics revealed that she has this one gene particularly positive," well, then, you could potentially consider ordering just that single gene rather than do multi-gene panel.

And in general, the cost difference is probably not much, and maybe even more sometimes in single gene testing. And so, it's possible to order multi-gene even then also. However, if you have known mutation in a family, ordering that single gene is something one can consider and one can do.

Host: Right. Right. So, it sounds like multi-gene is preferred most of the time, but there are situations when a single-gene test might work. And I'm sure, Doctor, folks really want these results, right? So, how long do results usually take? What kind of what forms do they come in? And how are they typically explained to, you know, non-specialists like me and patients?

Dr. Umangi Patel: Very good question. So, what happens is that once a result is obtained by a physician, first, as we discussed, that patients undergo basic understanding, Do you want this test or not? What are the implications for you and your family? And if patient says, "Yes, I want the test done," the test is done, insurance is authorized. The results are given to the clinician. Then, clinician will discuss with the patient that your genetic test unfortunately shows that this particular gene mutation is positive. This particular gene is linked with following cancer or cancers. And therefore, heightened surveillance and understanding about what can be done to detect things early or what can be done to reduce chance of that developing what are the risk reduction strategies and what are the chemoprevention type of medications if there are available in that particular gene mutation with associated cancer risk can be discussed.

So, the patients have to understand particularly which gene is positive, what does that mean to them, what type of cancers or cancer could be associated with that gene mutation, and does that mean patient needs to see a gastroenterologist or needs to see a breast surgeon or needs to see a GYN doctor or needs to go through mammogram, sonogram, MRI or needs to go through colonoscopy, endoscopy, needs to go through even meet with a urologist for prostate cancer surveillance or for any other GU malignancies, including kidney and bladder. So depending upon which gene mutation, the clinician goes over in plain simple words what it means to them and how do we help them understand and then refer those patients to a genetic counselor to have deeper understanding.

Host: Right. Right, what the next steps would be. And we were kind of touching there on prevention. So, I wanted to talk to you about some of the preventative options for folks who test positive for the high-risk cancer gene. You mentioned surveillance, risk-reducing medications, chemo prevention, perhaps prophylactic surgeries. How are these decisions for prevention individualized, Doctor?

Dr. Umangi Patel: So, each individual patient, depending upon which genetic test, mutation is identified and what risks patient carry, then let's say if it was an ovarian cancer risk, then patient is referred to a GYN physician or GYN oncologist to discuss that can we monitor this patient, because patient is still in childbearing age and wants to still have the family planning done.

Then, those patients are monitored with maybe transvaginal sonogram, a laboratory test, a physical exam. Once a childbearing age is completed and patient is not planning to have any more children, then those patients you can consider doing complete hysterectomy, including removal of both ovaries and the tubes to reduce the risk for developing ovarian cancer.

Nothing gives 100% protection because there is still a small chance that these patients can get peritoneal carcinomatosis, but major risk reduction strategy was applied. In breast cancer situation, it becomes a very personalized decision for the patient, herself, whether she would like to undergo bilateral mastectomy and reconstruction, or would she rather have heightened surveillance with biannual imaging rather than just once a year imaging.

So, every six months mammogram, followed by MRI. So then, mammogram sonogram is done in June, let's say, then MRI of the breast will be done in December. So, either you do heightened surveillance or you do risk reduction surgeries depending upon individual patient's preference. And as far as the medication is concerned, not in all cancer, did we have preventative medications available, chemoprevention.

But in breast cancer, we have tamoxifen, raloxifene, Arimidex. Such medications are available, and they reduce the risk by 50%. So, the risk reduction is there. It's not one hundred percent protection. So, that patient needs to understand. And so, follow-up questions can occur and arise. So generally, we ask patients to meet with genetic counselor and come back with the decisions.

Host: Right. Yeah. So, it's all individualized and patients may need some time to think about it, speak with family members and so on, right? It's been great to have you on, great to benefit from your expertise today. Let's just finish up and do a little myth-busting, if you will. Like, what are some common misconceptions among the public and even among clinicians about genetic testing for cancer risk? Like, you know, maybe a negative test means no cancer, right? How can these effectively be addressed during counseling?

Dr. Umangi Patel: So once again, when you receive a test result as a clinician and you sit down with the patient or patient and family, then you explain to them that, "Okay, genetic test is positive. This means that." If the negative test comes, that means that so far what we know in today's wisdom about what genetic mutations are identified and are linked with the cancer is available.

But if it is negative, that doesn't mean you are not at risk, then you fall back to the population risk. The general population is at risk for unfortunately developing cancer. And so, the risk would be same as general population rather than having increased risk related to that particular mutation. So, that means that patients still should undergo all of the surveillance that we normally do, whether it is prostate exam and PSA, whether it is colonoscopy, whether it is breast exam and mammogram and sonogram, or whether it is pelvic exam and Pap smear, whether it is taking proper history of the patient and see if there are any new symptoms that are developing that would lead to think of any of this potential cancer.

And then, even if you have a strong family history of cancer and yet your genetic test comes back negative, that means that there may be some mutation that we do not know today, but we might identify later on. Therefore, the risk does not become zero. Negative test gives some relief because then patient or the family members don't have to undergo screening, but the risk does not become zero, and patient has to understand that.

Now, if there is variant of unknown significance gene identified, kind of it is a self-explanatory term that it is a variant mutation. It is of unknown significance, meaning today we do not know what that mutation's significance is. However, two years, five years, ten years, twenty years from today, we might learn that what was thought to be of variant of unknown significance is actually significant.

Therefore, to have that database is important for patient and family to know, and once again, meet with genetic counselor. And then, periodically, patient and the physician should check that, "Okay, this variant of unknown significance, have we around to it, and have we understood or identified that now it is of clinical significance?" Then once again, that patient should undergo evaluation by the clinician who has ordered the test in the past or meet with genetic counselor one more time to understand what this mean today after we know from variant of unknown significance has become of some significance.

Host: Right. Right. None of us have a crystal ball per se looking to the future, but there's every reason to believe that we'll identify more and more genes or mutations, whatever it is, and having that information stored away would be helpful for patients and families and so on.

Dr. Umangi Patel: Science continues to advance. And so, this becomes a moving target, so to speak.

Host: Right. Absolutely. Well, I appreciate your time and your expertise today. Thank you so much.

Dr. Umangi Patel: You're welcome.

Host: And to learn more about oncology services, including genetic testing, visit montefioreslc.org. And if you found this podcast to be helpful, please be sure to share it on your social channels and be sure to check out all the other Doc Talk episodes. This has been Doc Talk, the podcast from Montefiore St. Luke's Cornwall Hospital. I'm Scott Webb. Stay well.