What is genetic testing and what does it mean for cancer patients? During The Breast of Everything podcast, Dana Zakalik, MD, a medical oncologist and medical director of the Nancy and James Grosfeld Cancer Genetics Center at Beaumont Hospital in Royal Oak, Michigan, talks about genetic testing, why it is important and how the newest advances in cancer treatment promise to make a significant impact on patient outcomes.
She begins the podcast by talking about the genetic mutations inherited from family members that can increase a person’s risk for breast cancer. Through a genetic test, clinicians can learn what those mutations are and what options are available for patients. The test is simple, Dr. Zakalik notes. The patient gives a blood or saliva sample that is sent to a lab specializing in hereditary genetics. The findings then are sent back to the patient’s physician.
“Through early detection of mutations, we can help manage and even reduce a patient’s risk,” Dr. Zakalik reports. “In addition, patients can tell their family members they may be at risk so they, too, can make informed decisions.”
Years ago, testing was so much easier, Dr. Zakalik explains, because clinicians only tested for the two known genetic mutations – BRCA1 and BRCA2. Today, there are more than 80 genes that can be tested. As a result of new technology, this number has exploded.
Scientific advancements, and more efficient, faster and less costly tests have changed the genetic counseling world dramatically, the genetic specialist finds.
When patients receive the genetic findings, they do have options, the medical oncologist reports. This is not a one-size fits all for patients. Imaging has improved dramatically over the years, which can lead to earlier detection. “We have many tools in our toolbox for patients,” she notes, adding that patients should consider other risk factors such as weight, lifestyle, level of exercise and hormone replacement therapy for example.
What Dr. Zakalik is most excited about are the advances in drug therapy for people with certain gene mutations. “This is a big, exciting development in cancer genetics because it can improve patient outcomes,” she is happy to report.
To hear about these new developments in cancer genetics, listen to The Breast of Everything podcast in its entirety with Dr. Zakalik and hosted by Comprehensive Breast Care Surgeons Eric Brown, MD, FACS; and Linsey Gold, DO, FACS, FACOS.
Welcome to the breast of everything podcast your trusted resource for breast health information support and encouragement. Your host today are Dr. Eric Brown and Dr. Lindsay gold of comprehensive breast care. Welcome.
DR. ERIC BROWN 0:15
Welcome to the breast of everything Podcast. I'm Dr. Eric Brown, and I'm here with my partner, Dr. Lindsay gold of comprehensive breast care. Today, we are very excited to have our guests Dr. Dana Zak click doctors, athletes and medical oncologists with more than 38 years of experience in her field, yet she remains very young. She serves as the medical director of the Nancy and James gross filled cancer genetic Center at Beaumont Hospital in Royal Oak, Michigan. Dr. Sackler completed a fellowship in hematology and oncology, from the University of Michigan hospitals and health centers, and is board certified in medical oncology. She is definitely a leading expert in the field of genetics. And today, we want to take a little bit time to talk about genetics, and the changes in the future. Welcome, Dr. Zack liqu, thank you so much for joining us.
Dr. Dana Zakilik 1:11
Thank you. I'm delighted to be here.
Dr. Linsey Gold 1:13
Yes, thank you, we know you are so busy. So we really appreciate it. And this is an excellent, excellent topic. And you, quite frankly, are one of the most knowledgeable people like ever on this topic. So we're excited.
DR. ERIC BROWN 1:26
So first, if we can take just a minute, if you don't mind, explain to the listeners exactly what cancer genetics is. And a little bit more about what you do at the cancer genetic center, and what your expertise in this field involves.
Dr. Dana Zakilik 1:42
Happy to do so. So cancer genetics is a specialty within oncology, where the focus is to identify individuals who are predisposed to develop certain types of cancers, and higher than average risk. And one they say that all of cancer is genetic because there are genetic changes that are acquired in one's tissue or once tumors during the course of development of a cancer. And then I'll there are also genetic changes that we are born with, that we inherit from mom or dad. And those are the ones that we focus on in our genetics program, where the idea is to identify who may be at higher risk of developing certain types of cancers. In terms of what we do in our program, our program is focused on evaluating individuals with a person or family history of cancer, or individuals who meet the growing list of criteria for genetic risk evaluation, patients receive pretest counseling, where we try to explain to patients, what genetics is all about why we're looking for certain genes, what the medical management implications are, so that we can properly inform our patients of what tests their their impact embarking upon. And this is very important so that patients are engaged fully in the process. With with proper consent, then we proceed to doing the genetic testing, which really involves collecting a sample either from the blood or saliva or other tissue, and analyzing it with with a laboratory that is really expert at looking at hereditary genetics. And that process is very complex, it involves a very precise detailed evaluation of the makeup of one's genes. And then at the end of this, we get a result, which is either negative meaning a person doesn't carry a hereditary cancer gene, or there is a finding that may be associated with increased risk, and we try to interpret that result and put it in the context of the latest evidence based guidelines for management. And the goal really, is to reduce risk, or and or do early detection, so that we can help our patients manage whatever risk they may be born with.
Dr. Linsey Gold 4:08
Well, you know, now that sort of the lay public is familiar, or I should say, more familiar than, oh, say five or 10 years ago with the term genetics because of ancestry and 23andme. How has that impacted or changed your conversation with the patient? Is it is it misleading to them to have these things available direct to consumer? Is it is it not? How How have you seen that enter? into our world? Yeah,
Dr. Dana Zakilik 4:39
I think for the most part, I think it's been great that the public is more aware of genetics and genomics, they're more comfortable with it. I think there's maybe less of a hesitation because it's all around us whether it's commercial testing, or articles in the in the media in the press about various genetic Topic. So overall, that's been a good thing. I think that there has to be a distinction made between clinical testing, which really is attempting to make medical predictions of cancer risk with associated management and risk reducing interventions, compared to direct to consumer testing, some of which, through certain laboratories may not be as comprehensive or may not contain the same types of genes that are directly related to a genetic risk for cancer. So some people refer to some of these direct to consumer test as kind of Recreational Genetics, they may inform us of certain things that are of interest, what percentage certain ancestries, somebody is, or whether they like cilantro or not. So there's quite a, quite a panoply of different genetic markers that make their way to direct to consumer tests. And whereas in our program, we really focus to focus on cancer related genes, and really try to make as scientific of our prediction, in as comprehensive of a way, whether someone is at increased risk or not.
DR. ERIC BROWN 6:18
Yeah, that's, that's terrific. Dana, thank you for that. It is a challenge for all of us when people come in and tell us they've done genetic testing, because they've done 23andme. And you have to explain the difference between that and one of the more cancer related places where genetic testing can be done. years ago, it was a little easier because there was just the BRCA one and two gene, some call it the bracket gene up, but now there's a multitude of genes that are tested. Why so many now? Can you give us a little background, like what happened, all of a sudden, there's an explosion in the number of genes that we're testing for?
Dr. Dana Zakilik 6:58
Sure, it's really been exciting to see the coming together of new technologies, which essentially made it possible for us to look at multiple genes. At the same time, using very sophisticated technology, some people call it next generation sequencing, which really has allowed the field to take off. So at the same time, that's that technology got better, more efficient, quicker, as well as less costly. Our scientific colleagues in the laboratory, have identified a growing list of genes that are associated with breast cancer or certain other cancers. So it's really the parallel world of scientific discovery of new genes, and scientific discovery of new techniques that make this all possible in the early days of our program. And really, in the early days of this field, we were limited by sort of traditional sequencing of genes or analysis of genes, which was cumbersome, costly, and the turnaround time was quite was much longer than it is now. And at that time, we focused on the what we consider the most significant important genes, as you mentioned, BRCA one and two, that kind of kick started this specialty, after they were identified in the mid to late 90s. And commercial testing became available in the late 90s. And since then, I would say sometime in the early 2000s, we we identified new genes, genes that previously were not well understood as possible genes associated with breast cancer and other cancers. And that list is growing. Some of these genes are what we call high penetrance. That means they're very high risk for prediction of cancer, others are just moderate, mild and even mild to moderate. So now we have a whole complement of genes ranging from the mild to the moderate to the high risk that we can include in a multi gene panel, that is, we consider it very, very comprehensive, in that it has well established genes, and some I call evolving gene. So these are genes that are still a little bit earlier in the discovery phase, but look like they're significant and relevant, and therefore they're included in the panels. So it's been really fun and interesting to watch the field take off with those scientific advancements, decrease in cost, a greater acceptance on the part of the community that genetics is something that is beneficial. We have more and more examples of why it's beneficial. So all all those things converge together to allow this field to become woven into the fabric of breast cancer prevention and treatment.
Dr. Linsey Gold 9:45
So I want to know, how often do you hear well, why would I do genetic testing? I mean, like, I don't want to know that I'm going to get cancer. I mean, why would I want to know that? Because I think we hear that a lot. Yeah. Talking about genetic testing. But you know, bringing up the subject of
Dr. Dana Zakilik 10:04
it. Yeah, absolutely. I think that we see patients, some who are completely on board and others, as you just mentioned, even just today, actually, I had a patient that essentially said, the very quote that you just stated, you know, typically, it may be someone who either may not understand that it impacts them, or it may even be someone who is somewhat skeptical. I do think that there's a natural human fear of too much knowledge amongst all of us in various forms. So I think that even now, I would say, a small percentage of patients are reluctant, and maybe are doing it just for their kids, they may say, you know, I'm and that's actually was a example of my patient today, who really wasn't interested in testing for himself, but wanted to know this for the kids and actually was very, I would say, kind of casual about it with reference to anything that could impact themselves, but definitely interested for their children. So I think this is still not an unusual sentiment, I think we in healthcare, have to do a better job to explain it to win the trust of patients. I think that a big topic now in medicine is, is disparate the topic of disparities and trust. And I think genetics does sometimes pose an obstacle when people don't really understand or, or even accept that this may help them I think, with proper conversation, gaining that trust, having a two way communication, I think in most instances, we are able to explain to patients that it may be a bit of benefit, but I think the initial human reaction sometimes is one of distrust or, or just lack of interest. Absolutely.
DR. ERIC BROWN 11:57
That's a very good point, Dana. And it's very timely, there was just an article published in the Journal of Clinical Oncology online last month talking about the implicit bias and referrals for genetic testing. So I do think it's a it's a big deal and something that we all as a medical community need to work on. I think your job definitely has gotten from difficult to really, really difficult because not only are more genes being discovered and tested for I think we can now test for over 80. But then sometimes patients get what is referred to as a variant of unknown significance. So an abnormal gene. But we don't treat according to that abnormality. Can Can you explain to the audience what is a variant of unknown significance? And how should we address those?
Dr. Dana Zakilik 12:47
Yeah, that's a great question and a very important one, we know that a certain proportion of patients who undergo genetic testing, get a result that is not black or white, it's not negative, it's not positive. What that means is that there's a variation or change in the spelling or in the letters that make up the gene. And it may be just a very minor alteration, and it may be very rare, it may be uncertain, pathologic cause significance, meaning that the alteration in the gene may or may not cause the gene protein, the product of the gene to actually function differently. So the laboratory performs a very sophisticated analysis where they look at a lot of features of that gene alteration. And those features may be functional studies, they may be clinical correlates, meaning that is it seen in people who get breast cancer at a young age, and so forth, and so on, there's quite a complex analysis. And at the end of that analysis, the lab may not be certain that it is actually truly clinically significant, meaning that it may not alter the gene at all, it may not allow to alter the protein. And so when that is a scenario where the lab is simply not a certain enough to make a very significant clinical recommendation, they will put it in the in the category of this V us or variant of unknown significance, which by definition is not actionable. There are many many of such variants of unknown significance. I think the more we do testing in all in amongst our population and other populations, that percentage of that uncertain will go down. But until it is reclassified as pathogenic or likely pathogenic, that result that vus is not actionable, and it does not change how we screened patients because we think it's part of the background variation that all of us have in our genetics. And I will say that there are times the laboratory may require certify it either go down downgraded to a likely benign or even upgraded. And that's why it's very important for us to stay in touch with our patients over time in case that reclassification may take place. So it kind of shows you that genetic testing results may not always fit into are clear, positive or negative.
DR. ERIC BROWN 15:20
But but but we do know that, you know, one of the old fashioned test results, having a BRCA mutation often led women to choose bilateral mastectomy. We know that that genetic abnormality generally speaking doesn't change the cancer that they have. But the chance of getting a second breast cancer is extremely high. But if somebody has a variant of unknown significance in that BRCA gene, we generally would not recommend any difference in in their surgical planning based on that variant. That's correct, right.
Dr. Dana Zakilik 15:59
Yes, that that is a very important point to make. And and I completely agree with you, it's very important to distinguish when a person has one of these uncertain variants or a VUS variant of unknown significance, that should not lead to risk reducing surgery or other preventative interventions, because really, that result is not thought to be clinically significant or clinically relevant. And until the lab reclassifies it as likely pathogenic or pathogenic, we should not be doing things that are certainly irreversible, you know, because it may it is not something that is warranted based on that result, that uncertain result.
Dr. Linsey Gold 16:46
So if we switch gears a literal and say, Okay, now we went looking for a positive result. And let's say, we do find one of those actionable genes. Rick just mentioned, you know, a sort of a more aggressive or a bigger surgery, bilateral mastectomy that we can do. But that's not the only way that a patient's genetic finding might impact treatment. Can you tell the listeners, why else it's important besides just oh, you need your breasts removed? Because there's a lot of other important reasons Apple would want to know.
Dr. Dana Zakilik 17:25
Yeah, absolutely. The most important thing is to emphasize to the patient, that they have options, and it's not a one size fits all recommendation, we definitely have to customize what we recommend to patients, or certainly the patient has to make the final decision, of course, but with our guidance, that high risk screening, high risk surveillance is a very well established option for patients who carry these high risk genes. We have made such great strides in the last five to 10 years in improving our imaging. And we know that screening for breast cancer is a very effective modality and high risk surveillance for women who carry the BRCA one and two genes, as well as some of the other newer genes definitely leads to earlier detection and well in most instances. And I think we're very lucky to have the expertise of our breast imaging folks at our institution, as well as other institutions who really do a great job at careful screening using either MRI, or some of the newer mammography techniques such as tomosynthesis, 3d mammography, as well as some of the improvements we've made in even in ultrasound as a screening option. So there are multiple choices that patients have for early detection, using all the tools that we have in our toolbox with respect to the high risk surveillance I just mentioned. And in addition, the field of pharmacologic prevention, it used to be called chemo prevention. That means taking a certain medication that's been known or proven to lower risk of breast cancer is really making great advancements. We know that there are estrogen blocking agents that can lower risk of breast cancer. We know that there are certain lifestyle interventions, there are several clinical trials opening for new medications to lower risk. So it's all about empowering our patient with with choices, and really allowing the patient to reach the best decision for themselves. That takes into account which gene as well as their own medical history and family history and other factors. So absolutely. I do want to emphasize that our job as clinicians is to inform, educate, and help guide our patient to the decision that makes most sense to them.
DR. ERIC BROWN 20:01
And I think it's important what you just said at the end there is it depends on the gene. Because you know, a lot of patients when you have an abnormal result, think that all genes are the same. So we've think of we've thought of the BRCA gene. Obviously, Angelina Jolie kind of brought that to the public eye with her preventative intervention. But actually, all genes are not the same. Are they?
Dr. Dana Zakilik 20:30
Yes, absolutely. We know quite a lot more than every year, I think we learn more about some of the new genes that have been added to the to the panels, and BRCA one and two started this specialty started this whole area of research. But we now know that there are some genes that are more moderate in their risk. So the light lifetime risk may be moderately are mildly elevated. And we also know that the gene doesn't exist in isolation. And what I mean by that is that also other risk factors that are inherent to a person's medical makeup such as their, their weight, their lifestyle, their level of exercise, whether they've been on hormone replacement, and other things that are unique to each patient also matter. So I do think that we we have established quite well, that some of the more moderate genes such as check to, or ATM, or genes associated with Lynch syndrome. So these are just other names that refer to other types of genetic risk genes that may not require one to be quite as invasive in terms of doing risk reducing mastectomy, and actually may allow us to manage the patient with enhanced surveillance at the right age and may not have to be as young as four BRCA one and two when we start doing MRIs at 25. So, indeed, the improvements in technology have really given us more options for the unique situation that each patient faces.
Dr. Linsey Gold 22:15
Yes, absolutely. And so along those lines, most recently, there's been some advances in drug therapy and how they relate to people with specific genetic mutations. Can you tell the listeners a little bit about that?
Dr. Dana Zakilik 22:35
Yes, this is definitely one of the big exciting developments in oncology and cancer genetics, which really is the product of what we learned in the laboratory about what does it mean to have a BRCA mutation? What does it do to the cancer cell? Why does it even cause cancer, and we know that the foundation of what having a BRCA mutation is all about is a defect in DNA repair. In other words, the cancer cell can't repair its own DNA if you have a BRCA mutation. So that led to the development of a whole new area of research of molecularly molecularly targeted therapies that target that attack that defect in the DNA repair. So you have a cancer cell that's rather vulnerable, because it can't repair itself when there's damage to the to its genetics. And if you give a drug called a PARP inhibitor, that's an abbreviation for a new class of agents or targeted therapies that are very precise, thus the the term precision oncology, and they only attack the cancer cell that has the BRCA mutation in it. And that has really allowed researchers to show tremendous improvement in outcomes for patients. And actually, these agents are now FDA approved for BRCA related ovarian cancer, breast cancer, pancreatic prostate. And what's really exciting this year, just a few months ago, is that for the first time ever, this new class of drugs has shown a benefit in women with early stage breast cancer. So those are the women where we can really impact the outcomes most significantly. Prior to this, the only approval for this agent was in more advanced breast and other cancers. So this is the first time we're moving these drugs further and further up the chain, if you will, to earlier stages when we really can impact outcomes because we can cure those patients and have essentially, you know the ultimate result and benefit for more women. And the reason this was such a big splash in the field of oncology is because this is a novel and rational and very powerful. Sighs type of treatment. It's an oral agent. These PARP inhibitors are for the most part oral, they don't cause hair loss, they don't cause all the side effects that may be traditional chemotherapy causes. And we hope perhaps someday we'll be using these agents for prevention, which will be really exciting. So this was big news at our oncology meetings. It was the first time ever, that the American Society of Clinical Oncology issued a practice update in a rapid kind of a rapid practice, change and improvement. And I think we in medical oncology, for the first time are using genetics to make decisions about how we treat systemically what type of agents we're going to give to patients. So very, very big news this year on the PARP inhibitor front.
DR. ERIC BROWN 25:54
Yeah, thank you, Dana. Yeah, this is every week, every month, there's something practice changing, certainly coming out. And this was a big, a big one for sure. For really speaks to why genetic testing needs to be offered to breast cancer patients in general, because as you mentioned, it really can can impact treatment, not only surgical management, but treatment. So fantastic. Fantastic. I, I have a question. And I know we're getting short on time here. And I really appreciate your time. I don't want to keep you longer than we promised. But is there a person that maybe shouldn't have testing? And if I may, a second question. common concerns that patients have really is in regard to if I get tested, what is it going to do to my life insurance, and ability to buy life insurance, and health insurance the same?
Dr. Dana Zakilik 26:55
Thanks for those are really very important questions and asked by many patients that we see in our clinic, in terms of what the downsides may be, or who shouldn't test really, there are definitely situations where you certainly any person who does not want to test I mean, at the end of the day, that patient has to sign a consent for it. And there may be some patients who tell us and actually this is still happening. Not that rarely where a patient says you know, I want to go home, think about it, or, or I'm not ready for it, or I'm anxious, I don't want to know. And then some patients who are elderly, who maybe don't have any children, so there's no impact on family members, and their elderly. And the result really wouldn't impact their management at all, either because of their advanced age where someone wouldn't likely be doing too much in the way of risk reducing surgery. So I think in those instances, either because of personal age related factors, or lack of family impact, or simply the patient really says to you, they just don't want to know this information. It may cause them emotional upheaval, that type of thing. And in that case, we tried to educate and be mindful and respectful a person's wishes. In terms of the life insurance question. Right now there's a federal legislation protecting against any health insurance discrimination. And that's the Ginola, the genetic information non discrimination act, there is not a set A similar law for life insurance. So theoretically, what we tell patients is anyone who doesn't have life insurance, and has time, we certainly encourage them to to obtain life insurance. However, in the real world, we have not seen any cases of life insurance discrimination for patients who get genetic testing. In other words, the courts are generally very in favor and and very much protective of patient's right to privacy and to understanding their genetics and genomics. So we haven't actually seen this to be a problem on any significant scale. But definitely patients are told that they may choose to get life insurance, and then come back and test at that point.
DR. ERIC BROWN 29:15
Thanks, Dana. That's important information, because it is a very, very common concern that concern that patients have before consenting to testing. So as we close up, are there any other messages that we haven't talked about or anything you want to make sure that our listeners are aware of?
Dr. Dana Zakilik 29:35
I just want to say that it's been really exciting to watch a field take off as much as this has the amount of knowledge that is all really leading to advancements, whether it be earlier detection, knowing who's high risk so that we can use our scarce resources and medicine to do the high risk surveillance that you need to do and do early detection. We know that if We detect breast cancer early, it's almost always curable. So I'm just excited that this field has really delivered on the promise of better medicine for patients. And I hope patients are not scared by it because it really the outcomes are getting better and better. And I'm really honored to be working with breast surgeons like yourself and and Lindsey, who have really carried the torch further and further in the field of breast cancer genetics. So it's a real team effort. And it's been a real privilege and honor to work with a team like ours.
Dr. Linsey Gold 30:36
Oh, likewise, we are so so happy to have you to lean on for your amazing information. Truly one of the brightest people I've had the privilege of knowing
Dr. Dana Zakilik 30:48
what Well, thank you. And I say the same to you both as well. It's just been a pleasure.
DR. ERIC BROWN 30:54
Well, again, if anybody out there is interested in genetic testing or genetic counseling, Dr. Zack colic is the medical director of the Nancy and James gross filled cancer genetic Center found at Beaumont Hospital in Royal Oak, Michigan. And I'm sure that they'd be happy to entertain patients questions through consultation. Thank you, Dr. Zack. Look for joining us today on the breast of everything. And thank you again to our listeners for taking time to play the podcast. I'm your host, Dr. Eric Brown, and I'm here today with my partner Dr. Lindsay gold of comprehensive breast care. Remember, we want to hear from you. If you have a topic you would like us to talk about we welcome your suggestions, you can send them to compress care.com that CO MP breast ca r e.com. Dr. Zack Glick Dana, as a friend and certainly as a respected colleague, I Dr. Golden, I both cannot thank you enough for taking a half hour to talk to us. I know this is hugely beneficial to our listeners, as you've been tremendously beneficial to all of the patients that you touch. And of course, selfishly to our patients that we very often send your way. So thank you again, and we look forward to working closely again and more in the future.
You've been listening to the breast of everything podcast with your host and board certified breast surgeon, Dr. Eric Brown and Dr. Lindsay gold of comprehensive breast care. If you have a subject you would like the surgeons to discuss, please email your suggestions online at comp Breast Care. com. That's co MP breastcare.com The doctors want to hear from you. The views thoughts and opinions shared in this podcast are intended for general education and informational purposes only and should not be substituted for medical advice, treatment or care from your physician or healthcare provider. Always consult your healthcare provider first.
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