This video features Elias Obeid, MD, MPH presenting on Disparities Research and Neoadjuvant. This presentation was given at our January 19th 21st Annual Highlights of the 2022 San Antonio Breast Cancer Symposium in 2023.
So thanks to the program directors guys man for inviting me today. So you'll see that I treat most breast cancer. So I don't treat prostate cancer. However, for the last 12 years I've been involved in cancer genetics. And if I say five years ago, would I have been invited to give a talk like this? Probably not. And things have changed significantly and to the better for prostate cancer risk, prostate cancer and genetics. So this is really a new and recently developed field. Just a little bit of background. In 2014 of 2015, I was asked to lead the prostate risk program after someone else who was doing this at Fox Chase left. And I thought, well we are not doing much in genetics, but there is some studies going on and we kept on doing things and really between 2015 and 2017 things have really changed significantly in the area. So without further I'm gonna delay. I'm going to just talk a little bit about what we have. So this is just a list of some of the funding I have and none of the stuff I will be discussing today is rated to anything that I have funding or is it for? So we will talk about territory. I'm sorry, prostate cancer syndromes and genes, genetic testing needs in the area. What is genetic testing based screening? And of course all of us have a lot of questions about who needs to be screened and what do we do for them. But I will be focused more on the genetic sport and cascade testing. It's an area that we will be part of as we identify people who have a genetic predisposition to cancer. And of course there's psychosocial distress that involves genetic testing for the individual as well as their family members. And it would not be correct if we just end this without talking about the disparities that would affect people and who does, you know, it's important for for for our care. So prostate cancer of course it's well recognized to have a strong heritable factor or component to it. And for many, many years we've known that somebody with their family history of prostate cancer, they are at higher risk, but it was long overdue other than knowing about the B. R. C. A. One, maybe B. R. C. A. Two, there is an association and the risk of prostate cancer. I think it took a while before we could know more about that. So the incorporation of genetic testing really took place in the last five years uh for the most part and with that said there were several genes that have been identified and have been linked to prostate cancer. I'm going to name those genes and many of you probably are familiar with the B. R. C. A. One or two genes, some people call them braca one bracket to lynch syndrome or the lynch genes. The other newer genes to the field are ATM gene mutations. Chek two gene mutation that all those have been discovered to be contributing to prostate cancer risk or what we call hereditary prostate cancer. So genetic disposition in DNA repair genes and for the most part, all those genes is in one specific group of genes. We group them as a DNA repair genes and they are found probably in somewhere between 11 or maybe 10% to 15% of men who have metastatic prostate cancer and maybe about 5 to 7% in men with localized prostate cancer. And you can look at this and say, well, You know, this is like a small percentage. But if you look at the number of men who have prostate cancer per year and you just say anywhere from 5 to 15% of them are going to have a genetic predisposition and just think about how many individuals and their families could also be affected. So that just gives you the sheer numbers of individual who can be prevented from having cancer or early detection etcetera and other members in the family who would benefit from this. And that's not even touching based on the effect on treatment for those individuals who are affected with the disease. So the germline DNA repair gene mutations in one study was just published maybe about four or five years ago that looked at men with metastatic prostate cancer. And they found that about 82 out of 692 individuals have germline mutation in one of those genes BRC 2 80 M. Check two and B. R. C. A. One. So that was the similar. The first one study that really looked at was an eye opener basically about this. And this was replicated in some other studies with similar prevalence rates in metastatic castration, resistant prostate cancer cohorts. So in spain, one study looked at it and found that it's about 16.2%. Another study from the United States 12% Canada 7.5%. And I think, you know when when we look at genetics, it's very important to realize that there are populations and population is different. And as you look at one homogeneous population, you might have different numbers from when you look at a little bit more heterogeneous population. And that's why those numbers might not be exactly the same, but they're all in a very similar range. So similar similar results were seen also in the metastatic hormone sensitive prostate cancer. Again about nine or 9.4% in one study. And the prevalence in high risk localized population was again, as I mentioned, more than 5%. So all those numbers really point to the importance of recognizing genetics and the importance of genetics in patients who have prostate cancer or may be at risk of prostate cancer and their families. So I don't expect you to remember all this on the study. And I think my colleague doctor might talk a little bit more about department inhibitors and what is targeted therapy for prostate cancer. But in those studies that again from 2015 2016, that looked at partner inhibitor used, which is more of a targeted therapy for the BRC one BRC two and other DNA repair gene mutation related cancers. So you can see that many of those have had good responses, improved outcomes when part inhibited or targeted treatment was given. And I'm going to have to talk more about this. And so so clearly recognizing a genetic predisposition is not only related to risk And two families but also to treatment in those individuals. So now that I've told a little bit about how important it is recognizing the numbers and the effect on treatment. Of course. Now in the last four or five years we have noticed that genetic testing is more widespread and more widely available. So the discovery, as I mentioned that men with metastatic prostate cancer are more likely to carry germline gene mutation and the approval of port inhibitors for the treatment of men with prostate cancer in certain settings. That highlights the importance of genetic testing in men with prostate cancer. So challenges and more challenges ahead of us and the future of genetics and prostate cancer is just not done. I think we're still looking and others are still looking at how we can improve and what we can understand about the genetics because it doesn't what we know now doesn't explain everything that we know about the genetics and predisposition in prostate cancer. So what are the trends? So multiple professional organizations now recommend integrating genetic testing as part of prostate cancer treatment. And it is now advised that most medical oncologists should be very familiar with genetics. Now we don't expect them to know all the details about the genetics, but at least know the patterns of referral. We know that in metastatic prostate cancer there's no question they're going to be referred. But sometimes even in earlier stages of the disease, some men might benefit from the referral to genetics and I understand that the genetic component or the availability of a genetic counselor may not be available to everyone. I think at Fox Chase we are lucky to have a department of clinical genetics which is very helpful for individuals when they are not sure if they need to refer patients or not or test someone or not. But there are different websites and that can be accessed, putting zip code about finding genetic counselors. So for those who are in more distant areas, they can just go to find the genetic counselor.com and put a zip code and they'll have a zip code area maybe of 10 miles 50 miles if they are energetic counselors so that they can refer patients to them. And I think this is important for those who are not very familiar with genetic testing. So I think importance is in decisions about screening risk assessment for individuals for their family members. We know that there are difficult tasks ahead. So what is clinically relevant gene? We definitely know about the BRC one BRC two. They are clinically relevant for the individual as well as their family members. And put their the at risk family members. There's also remember medical legal liability. So, for someone who should have been tested and did not get a referral, that's also liability. Of course, I think more of our ethical importance of us managing patients, giving them the best chances of prevent prevention and treatment. And again, I mentioned there's scarcity of genetic counselors and not all the areas this is available. If you look in philadelphia, you can find a genetic counselor within just a few miles from one cancer center to another. But then you would go somewhere else and it could be like probably an hour or two of dr for some to find a genetic counselor. And lastly, I wanted to mention that financial concerns are important concerns for patients. Many times, patients are referred to get testing and they put it off or they don't want to do it because they're worried about testing is going to cost them. Is that going to cost them something else like insurance discrimination. And that is a very valid concern. And I just wanted the honest to know that as of 2008, there is a federal law called Gina or genetic nondiscrimination act, which which is really good for patients who have a genetic predisposition. That would prevent any medical insurer from providing insurance to them based on genetic data. Now that does not apply to life insurance, which is not vital for health care or long term disability insurance. So certainly there are still some discrimination that some individuals with genetic information they can face, but at least not for health care insurance, which is I think important. So just putting this up at why to do testing and who to test. And I borrowed this from some of my colleagues dr chang hood at Washington University. So again, in localized disease, this is going to be important in in the metastatic disease, whether it's castration sensitive or resistant disease or biochemical recurrence. So in multiple settings. And again, this continues to change. And for those of you who sometimes ask the question, where would I find the information may be going to the guidelines and guidelines. There are two areas, even the prostate cancer section or in the genetics and or prostate cancer risk assessment section where you will have the information about who to get genetic testing and to be considered. And initially it was for metastatic prostate cancer and some individuals with early stage disease. I think the guidelines have been changing as the information has been changing, but as guidance. So anybody with the high gleason score, certain populations and jewish populations etcetera. They should consider getting testing if they have other members and their families with different cancers like breast cancer, ovarian cancer. And the reason I mentioned this is because the BRC one BRC two genes are linked to again, the syndrome is called breast ovary cancer syndrome. Although I'd like to say breast cancer, breast cancer, ovary and prostate cancer syndrome. Now, since prostate cancer is really part of this. So guidelines, I think it's an important place where you can go to get all that information. They added that not just the BRC one and two genes, but also I put here the lynch syndrome genes, four or five genes that are linked to we know colon cancer over the cancer. And more recently, prostate cancer is part of this syndrome and as I mentioned, the ATM gene probably two and check to genes. So counseling and testing. Traditional clinical care delivery model has been two visits. I believe it's still important. From 1997. It has been that patients should get counseling informed decision if they want to do testing or not and then they get the test and then they come back or they get their test result. Keep in mind that when somebody gets testing, we know that most of the individual who gets tested are going to end up with a negative test result. The highest time. You know, the highest chance actually 50 50. When we know that someone, let's say a man comes to us and has a brother with a B. R. C. A gene. And you know gets testing that we know it's a 50 50 chance. But for everyone else it's going to be anywhere from, as I mentioned, 10%, maybe up to 50%. So the chances are they going to get a negative test result and giving them the information on the positive test result is very important. But equally important. Also telling someone what does the negative test results mean for them for their family members as well. So that's where the post test disclosure or the visit where we give them the result is important just to tell them and educate them about what they need to do. So the visit I mentioned is important and that is the visit that potentially can initiate what we refer to in genetics at as cascade testing, cascade testing is when one individual is found to have, let's say we are say one mutation, then we know that the siblings nephews nieces et cetera. They are at risk. So that that's where the 50 50 chance comes into play for that family and initiating and telling them about their family members were typically review with them, their family three. We go over who is like their parents, grandparents, Children, siblings, nieces, nephews, etcetera. And we point out to them who is going to be important to get testing. So that's what initiates cast is testing. You can think. A man comes with metastatic prostate cancer to doctor Congressman Clinic and then he refers them to me and was found to have a B. R. C. A. Two gene mutation and for that individual now his daughter that's safe. She is 40 years old or 35 years old. That's going to be a 50 50 chance for her to get the B. R. C. A. Two gene. And of course we know that is called breast cancer, early detection with breast MRI's etcetera prevention of ovarian cancer. So you can see how where that leads. So from one individual to another and more in their family. So I wanted to bring to your attention that consistent data from multiple studies looking at this, it showed that there is no long term adverse psychological outcomes for those tested individuals. And we know that from the data from breast cancer patients who got tested for the BRCA one and two genes many, many years ago and more and more research is being done for men who are at risk for certain genetic predisposition syndromes. And there's one study that families with lynch syndrome, there was more of an anxiety between the time of telling someone that you might have their lynch gene until they get the test results. So once they get the test results that anxiety level goes down really just because they know what to do. So it's really important. I don't think that anxiety is actually should not prevent them from doing a genetic testing. And of course we have more uh you know to be done in that area. So I mentioned already all those gene mutations a lot needs to be done. I mentioned already that the hereditary breast and ovary cancer syndrome or H. B. O. C. I. Put the P. And many others who do the genetic field, they would like to put HBO PC because prostate cancer is part of that syndrome. Again, I mentioned the traditional model of testing with telemedicine things have changed the last two years. Maybe one good thing about covid that happened that we started doing things more remotely. I think for many, many years we were very focused on bringing patients in for the testing results later on and now we're allowing things to be done remotely genetic testing. While traditionally we've been doing it through blood testing now we can do it through saliva tests so someone can sit at home meet with us virtually, we can have a slider kit sent to their home, they'll get the instructions how to do the testing, they ship it and they get the results and of course we help them understand the result. So all those models have been changing in the last two years and I think that change is for the better and this is really good for individuals. And I wanted to definitely discuss this whenever we think about models of testing and how we deliver the information to patients and their families, we have to always be very cognizant that what we do. It has to be applicable to all. And I mean to everyone, not just to those who have access. So it should be accessible to everyone. And we have to think about population and at risk population and make sure that the care that we deliver is not desperate. So those are some of the genes that we do. So when you send your patients with prostate cancer, these are the typical jeans I've mentioned. The B two B one B 13 is probably the one gene that is not in that DNA repair pathway. But it was discovered that it has a very higher risk to developing prostate cancer in those families. And what is nice about this table that it just puts what's the level of evidence for the data that we have. Clearly the highest level of evidence we have is for the bracket to braca one gene. And more recently for some of the lynch genes. And it gives you some of the information about what are the risks. And keep in mind that the risks are wide intervals. You can see something from 7.5 to 30% and really that depends on the particular gene, the particular population. And I think with time we probably will have a little bit better numbers and assessments as we understand more and we test more people. And just 10 years ago, very few individuals with process cancer were getting genetic testing in the last five years, this has been widely available and I think in the next five years we're going to learn a lot more than we did in the last decade. So just to give you some examples on what the risk is. So for me, I say one and two gene mutation, there are about 44 fold increase in the risk for braca one about six fold increase in the risk with bracket too. And not only just an increased risk of developing prostate cancer, but you know, we know that it's more aggressive prostate cancer and they can have a higher score more advanced stage at the time of their diagnosis, more likely to have nodal involvement or metastasis even at the time of their diagnosis. And of course studies have shown that they can have even a shorter spent to recurrence. Just to show that from one study, its retrospective analysis of almost 1300 individual with prostate cancer, the media follow up 64 months. It clearly showed that the metastases free interval is shorter for those with the B. R. C. A gene mutation as opposed to those without a mutation in the same cohort. So they are independent bracket genes are independent prognostic factors. Again, germline mutation, positivity may affect men's future cancer treatment. I mentioned department inhibitors may be a decision about whether they want to do surgery or radiation and of course those patients, they have a higher risk of other cancers. So once they are identified as having a BRC TWO A mutation for example, they need to discuss with someone about the risk of male breast cancer. That risk can be anywhere from 8-9% over a lifetime. Just to put it in perspective, it's small, but a woman's risk without family history of breast cancer or a genetic predisposition to breast cancer. Her lifetime risk for developing breast cancer is somewhere between 10 and 11%. So we're talking about the man with the BRC two mutation whose lifetime can be 8 to 9%. And that is not far off from that 10 to 11% for women. And we tell women you need to get a mammogram. So some of those men I follow many men with two in my clinic and we we recommend at least maybe to start with the mammogram and later on depending on the breast density, whether they want to continue with that screening, There are other cancers implicated. There is a risk for pancreatic cancer. We used to say about maybe 4% lifetime risk. Now we think it's 5-7% risk. We're learning more about who would benefit from pancreatic cancer screening. There are some tests coming up in the next few years, such as the liquid biopsy that could help with early detection of some of those cancers and some other cancers like melanoma. So as it's important for those who are affected with prostate cancer. The testing would be important for those who don't have prostate cancer diagnosis. So prevention and putting here how to do the screening. So some of the other genes like chek two mutation is the risk of male breast cancer, prostate cancer and of course other female related cancers I put here the A. T. M. Jean, just for you know that there are studies that showed it's linked to prostate cancer risk and benefit from proper inhibitors. MBN is another gene that maybe is linked to prostate cancer. I think we're learning more about it, lynch syndrome. Think of colon cancer over the cancer, uterus cancer and prostate cancer is added to that. So I don't want to just overwhelm you with all this data. So a lot of things. So genetic, the informed screening, you can look at multiple organizations. They are recommending the same thing for individual who have prostate cancer at risk. More research is needed and their ongoing clinical trials in the field, of course, psychosocial concerns are something that's valid and good thing to address with individuals and genetics. We are capable of addressing that. So just don't hesitate to refer to the patients. I already mentioned the cascade testing. So I don't need to emphasis that already you will see those in the slides or in the recording of this. Very important because going to affect individual and their families can help with early detection and prevention of disease. With this, I thank you for your attention and ready to four questions later on.
