Myriad Live episodes are recordings of an open-forum webinar hosted by Dr. Thomas Slavin. The opinions and views expressed in this recording do not necessarily represent those of Myriad Genetics or its affiliates. To participate in a future recording, visit myriad-oncology.com/myriad-oncology-live for a list of dates, times, and subjects.
References for this episode:
List of accepted abstracts from 23rd Annual American Society of Breast Surgeons https://www.breastsurgeons.org/meeting/2022/https://www.breastsurgeons.org/meeting/2022/docs/2022_Official_Proceedings_ASBrS.pdf
Kurian et al paper. https://jamanetwork.com/journals/jama/article-abstract/2600457
Highlights From the Miami Breast Cancer Conference 2022— Co-chair Debu Tripathy, MD, provides an overview of the studies discussed at the meetinghttps://www.medpagetoday.com/meetingcoverage/mbcc-video-pearls/97669Abstracts:https://www.cancernetwork.com/journals/mbcc-suppl/38th-annual-miami-breast-cancer-conference-abstracts-miami-breast-cancer-conference-abstract-supplements
0:00:13.3 Speaker 1: Welcome, this episode of Inside the GENOME is a recent recording of Myriad Oncology Live, a webinar hosted by me, Dr. Thomas Slavin, Chief Medical Officer for Myriad Genetics. The opinions and views expressed in this recording do not necessarily represent those of Myriad Genetics or its affiliates. To participate in a future recording, please visit Myriad Live for a list of dates, times and subjects, I look forward to exploring the world of genetics with you all.
0:00:41.2 S1: Hello everyone, welcome to Myriad Live, hope you're having a great day. We have an exciting talk today, we're gonna be talking about Spring Oncology Conference Review. Shelly Cummings, who is normally helping out on the chat is gonna be really running this one, and we have some great presenters, so I'll defer to her in a second. A little housekeeping to start, as always, we are now recording this, so definitely I encourage you to unmute yourself, ask questions, but if you don't or don't wanna be recorded or whatever, we just use the audio. But you can always either... We can have it as... People can also send messages to me today, I can run the chat if you wanna do a little stewarding Shelly of the [chuckle] presenters.
0:01:39.9 S1: And yeah, just let me know if you have some questions and we can make sure we get those put up. I would assume people can see this right now. Yes, and so next month, we're gonna be talking Mental Health Genomics, so May is Mental Health Awareness month, so it's a fitting topic, and then we're gonna be talking about emerging biomarkers for Li-Fraumeni Syndrome screening. So there was some recent research presented on liquid biopsy early detection, so that's what this will be kind of largely focused around. We do have talks being planned out June, July, so those are just not posted yet, but we're trying to do about two a month on average, kind of one in the first half of the month and one in the last half of the month currently, so it's a pretty good pace. And Inside the Genome podcast, we've been putting a bunch of podcasts, we just learned last week that we broke 4000 downloads on this, so somebody's listening to it, so thank you out there for listening, [chuckle] it's exciting. We have been putting anything that was from these webinars, it just says "Myriad Live" in front, and then anything that is not from these webinars, we just don't have Myriad Live in front.
0:03:00.7 S1: Again, probably not the best system, but if you've listened to one or two, you'll get it real quick, because these tend to be just me sitting down with one person, like this one was with Allison DePasquale, now we have a bunch more to post right now. And those are usually about 15-25 minutes or so, and then Myriad Live, obviously, is just the audio from this. We've been putting the links in, like this last one on Advanced Practice Provider Genomics, we've been putting... Trying to put all the links in. I mean, this was... There was a lot going on for this podcast, so it was great. We had a fantastic discussion by a lot of experts. So, if you didn't listen to this one and you wanna hear about all the opportunities for these types of advanced practice certifications and training, this was a really a top notch Podcast. And we put a lot of the links in the chat here, so also thanks to Shelly largely, so thank you Shelly, for helping out there.
0:04:03.9 S1: But that one, yeah, a lot of acronyms flying around, so you might have to listen to it two or three times, if you're looking for best opportunities for training. So with that, let me introduce Shelly Cummings, I think everyone... A lot of folks know her on the line, she is our Vice President of Medical Oncology Medical Affairs, and really runs the medical affairs for the Medical Oncology Division. And Shelly, I'll let you talk about what you have planned today, and then take it from there.
0:04:38.7 Speaker 2: Okay, thanks, TJ. I have the fortunate opportunity to lead a fantastic team of regional medical specialists and MSLs who attend conferences regularly and take notes and are really diligent with coming back to all of us and giving us the key highlights. So I might be guiding this conversation a little bit. I really have to say that they are the ones that are gonna be leading these discussions and have chosen the specific articles to pull and to highlight. And we've built this out so that there will be plenty of questions or plenty of opportunities for questions and answers. Again, if you want to post something in the chat, you can unmute yourself or you wanna send something directly to TJ, feel free to do so, but we wanna try to keep it as interactive as possible. And I'm gonna introduce everybody all at once, so we can flow into this. The first regional medical specialist that's going to give us an overview of the highlights from the Society of Gynecologic Oncologists or SGO, is Chandrika Kurpad.
0:06:00.9 S2: And so, SGO theme this year was called Building Bridges and Breaking Barriers, and it was a hybrid format, it was very well-attended, I attended it. I felt like it was very well attended for not having conferences for two years, and the level of excitement was pretty elevated. The audience is clinicians that are focused on care for women for gynecological cancers, fellows, nurses, handful of genetic counselors. But it's not a heavily populated genetic counselor meeting and gynecologist obviously. And Chandrika is gonna lead us in oversight of this meeting and highlight some of the several interesting studies. Most notably there's a lot of attention in endometrial cancer. And then obviously we'll talk about ovarian cancer. I'm gonna pass it over to Chandrika to share her slides and walk through this and read questions at the end.
0:07:05.7 Speaker 3: Thank you, Shelly. And hi everybody. It's great to be able to present highlights of the SGO conference to all of you. Give me one second to share my screen. Do you see that in... Do you see it in presenter mode?
0:07:28.7 S2: You need to swap it Chandrika.
0:07:32.5 S3: Swap.
0:07:32.8 S2: We can see your next slide giving us a preview.
0:07:37.4 S3: Just a what?
0:07:39.1 S2: There you go.
0:07:40.9 S3: Okay. Perfect.
0:07:41.0 S2: Very good.
0:07:41.1 S3: Alright. So it's great to be able to share with all of you highlights from the SGO 2022 annual meeting. And yeah, here we go. Okay. So I'm gonna highlight a few studies in the ovarian cancer space and finish up with a few studies in the endometrial cancer space. So this first study was presented by Dr. Kathleen Moore in which they looked at the evolution of the ovarian cancer treatment paradigm in the United States and Europe. And this was a chart review study of more than 5,000 patients with advanced ovarian cancer. And what they found was that 18% of these patients did not have germline BRCA testing, and 79% of these patients did not have homologous recombination deficiency or HRD testing on their ovarian tumors. And so, this study highlighted unmet needs since there's been dramatic and rapid advances through clinical trials in the use of PARP inhibitors and PARP inhibitor combinations for these patients. And we need to increase germline and HRD testing in the ovarian cancer patient population to improve treatment planning with approved therapies for the best outcomes for these patients.
0:09:17.6 S1: Chandrika where... So what was the cohort here? The...
0:09:21.4 S3: It was...
0:09:22.6 S1: 5386?
0:09:23.3 S3: Right. It was 5386 patients in this analysis treated across the United States and several countries in Europe. All patients had stage three, four ovarian cancer.
0:09:35.3 S1: Yeah. But just from various academic centers or something? Oh, okay. Yeah.
0:09:40.1 S3: Yeah, from academic centers and I believe academic, I'm not sure if they included community practices as well. But it was several countries across Europe, as well as the United States.
0:09:51.9 S1: Yeah. 'Cause this actually looks... To me, just at a high level pass, this actually looks pretty decent. 18% did not have germline testing.
0:10:02.1 S3: Yes, but I...
0:10:04.2 S1: Because usually even good academic centers were batting like 60% to 80%. And the data we had from Allison Kurian over the last few years was anywhere from like what the last paper was... Her one paper was I thought 30% or something. I think the last one was much higher. So it's definitely tracking up. And it seems like from talking with the lot centers most are now starting to get into that 80%. So this is pretty good to some extent.
0:10:27.7 S3: Yeah.
0:10:29.1 S2: The other thing I wondered about is the chart review timeframe, was it earlier in...
0:10:36.0 S3: It was 2017 to 2020. Yeah, 2017 to... And Dr. Moore did acknowledge that in her presentation at SGO where she said, 18% not having germline BRCA, we think that's a good number to reach. And she knows... She realizes that we're not at 18%, not getting testing in the real world, it's really much higher number of patients from getting tested.
0:11:03.4 S1: Yeah. It's always interesting to me though, because the ovarian guidelines, testing all people with ovarian cancer, I think those originated in 2006, don't quote me there, but I believe, 'cause I was... We were trying to figure it out one time for a grant with the NCCN...
0:11:21.5 S2: I think 2008.
0:11:23.1 S1: Okay. Yeah. Somewhere right around there. So it's been some time obviously, whether it was 2006 or 2008.
0:11:31.2 S2: Yeah.
0:11:31.3 S1: And it is interesting that when I personally think about estrogen receptor for instance, or like... It would be almost unheard of to not have estrogen receptor typed on like a breast cancer. Clearly that probably predated whatever 2006, 2008, but there... It's interesting that there still remains... There's some things that are so rote and germline testing, even though those guidelines have been around for so long remain just a challenge to integrate across all health systems.
0:12:02.8 S3: Absolutely. We need to do better to help these patients.
0:12:06.8 S2: Chandrika, what does it mean by 55% received one LM?
0:12:12.9 S3: So in this study they reported that 55% of these 5386 patients received first line maintenance, either with a PARP inhibitor or bevacizumab or some form of first line maintenance treatment. And this receipt of first line maintenance treatment varied by countries. So it was different in different countries. It did increase over time in most countries, as the knowledge from those clinical trials was dissipated among the communities. And 45% of the patients did not receive first line maintenance. They had active surveillance only. Any other questions? Alright, so let's move on to the next study I wanted to highlight. I'm having trouble going to the next slide. Oh, gosh. Sorry about that.
0:13:15.4 S1: And you might need to re-share something, sometimes it gets a little strange.
0:13:19.7 S3: Okay. It's stuck. Okay. Sorry about that. Okay, do you see it in the presenter? There's a lot of pics here. There we go. Okay. So this study was presented by Dr. Katherine Watson, and it was the result of a prospective randomized non-inferiority trial of video-assisted streamline genetic education and testing for patients with ovarian cancer. And in this study, 59 patients were randomized, 28 in the traditional arm where they met with a certified genetic counselor underwent genetic counseling and testing, and 31 patients in the streamlined arm where they underwent video-assisted education and then made a decision on whether they wanted to or not wanted to go ahead with an ovarian-focused gene panel.
0:14:26.0 S3: Both arms had results disclosed by a certified genetic counselor and patient's psychological impact and distress were assessed, both post education and post-results disclosure. And interestingly, what they found was that the mean post-education and post-results distress scores were higher in the traditional arm rather than the video assisted arm, the streamlined arm, although this difference was not statistically significant. And what they concluded was that they need larger studies, adequately powered to detect that difference to confirm these findings, but this study suggests that alternative pre-test educational models may simplify this genetic education and testing process without negatively impacting patients and may help us to help more patients with ovarian cancer get that germline genetic testing that they need to make those treatment-related decisions.
0:15:31.6 S2: So, Chandrika, I found this one an interesting study, and I'd love to hear your and other people's opinions on why you think the traditional model resulted in higher distress scores?
0:15:49.9 S3: So I'm gonna start... Sorry, were you gonna say something, Shelly?
0:15:52.7 S2: I was just gonna say, even though it wasn't statistically significant it's still...
0:15:56.3 S3: Right, keeping mind it was not statistically significant, my thought on it was that perhaps it's the amount of information offered or perhaps it's for patients, the stress of perhaps another medical appointment. It could be a multitude of reasons. What are others thoughts on this?
0:16:21.6 Speaker 4: I agree with Chandrika, that sometimes getting more details about this information might increase stress, but also perhaps there was something about the energy of the appointment, maybe the genetic counselor was transmitting some anxiety as well, when educational videos tend to be a little bit more... If not upbeat, pretty neutral. Based on the experience that I have for our pre-test education videos with the patient education team, the video is pretty... It's not alarming at all, and it's designed that way, so I'm thinking maybe that has to do with it.
0:17:12.5 S2: That's a good point. This isn't the first study that has highlighted that phenomenon, and I just wonder if there's... Where that is gonna take the field. We do alternative delivery models now, but I just wonder if the authors could highlight or eventually with a larger study, highlight what elements were the key elements that tip somebody to more distress or less distress, or if it was just the venue, face-to-face, white coat syndrome, and/or upbeat video, 'cause I think there's things that we can pull apart there that might make it more impactful for certain patients.
0:17:55.8 S3: Absolutely. Alright, and I'm briefly going to mention this, one of the sessions was called Great Gynae Debate, and one of the debate topics was whether all patients with advanced ovarian cancer should be offered a PARP inhibitor? The pro side of the argument was presented by Dr. Neu, in which she highlighted that there were multiple trials showing benefit in the front line setting, the Prema study particularly demonstrated PFS benefit for homologous recombination proficient patients, and that the HRD testing is a proxy measure of homologous recombination deficiency in the tumor.
0:18:40.0 S3: The cons were presented by Dr. Wethington, in which she highlighted that patient selection is important. This is targeted therapy here, and we're trying to choose the right drug for the right patient at the right time, and the ITT data may not give us information on the magnitude of benefit for patients in all sub-groups and these drugs are not without toxicities, both side effects as well as costs are associated with this treatment. Now, each doctor passionately argue their position in the debate in the Q&A and discussion afterwards, both of them agreed that they do discuss it with patients and make a shared decision with the patient on whether a PARP inhibitor may be appropriate and that the patient should get to choose what is most important to them.
0:19:32.5 S3: Alright, with that, I'm going to move on to endometrial cancer, now, with ovarian cancer... With all of these advances in treatments, the mortality is declining but with Endometrial cancer unfortunately, the mortality associated is trending upwards, and that's not a good thing, and the rates of aggressive uterine cancer subtypes are rising in the United States, particularly among non-Hispanic black women. And one other brief piece of background I wanna review before we dive into the studies is that Endometrial cancer is classified into four molecular subtypes, the tumor may be POLE mutated, MSI high, it may be copy number high, typically with the TP53 mutation, or it may be a copy number low with wild type TP53, these types are also called NSMP or no specific molecular profile and looking at outcomes for patients with these different molecular profiles, the POLE patients perform the best and the TP53 mutated patients have the poorest outcomes and guidelines currently recommend that we consider comprehensive genomic profiling to identify these molecular subtypes in the initial evaluation of patients with Endometrial cancer.
0:20:54.9 S3: So here's the first study I wanted to present on Endometrial cancer, this is presented by Dr. Amy Jamieson looking at molecular subtypes stratified response to adjuvant therapy. So this was an analysis of institutional and population-based cohorts of Endometrial cancer that had undergone molecular classification, about 2500 patients were included, all four molecular subtypes were represented and they reviewed responses to adjuvant therapy in a radiation or chemotherapy, in all of these subgroups. And what they reported was that a percentage of POLE mutated Endometrial cancer patients were possibly over-treated, a proportion of P53 mutated Endometrial cancers were possibly undertreated, and that chemotherapy significantly improved outcomes in P53 mutated Endometrial cancer, but did not add much value to radiation therapy in mismatch repair deficient or no specific molecular profile Endometrial cancer, and what these findings support is that we need to be thinking about molecular subtype-directed Endometrial cancer trials... Clinical trials, and the deescalation of adjuvant therapy for POLE mutated Endometrial cancer so that we're not over-treating or under-treating these patients. Any thoughts or questions on this one?
0:22:28.3 S2: Yeah, so it looks like we have a question in the chat from Cindy Snider.
0:22:31.9 S1: Yeah.
0:22:32.5 S2: Asking if there's any association with the age of diagnosis with a particular molecular subtypes?
0:22:40.6 S3: Not that I'm aware of over the top of my head, does anybody else on the chat or on the...
0:22:46.5 S1: Yeah, I've not seen anything, not to say there might be something out there.
0:22:54.4 S3: Yeah, but we can certainly look into it and see if we can provide some detail offline.
0:23:02.8 S2: So another... Dr. Bollin is asking a question whether POLE mutated patient is treated with ICT?
0:23:13.0 S3: Can you expand on ICT please?
0:23:18.1 S2: Let Dr. Bollin unmute himself.
0:23:19.6 Speaker 5: Yeah. Immune checkpoint therapy, because those hyper-mutated tumors ought to be more... Have a lot more Immunogenic Peptides and I'm just wondering why they do this.
0:23:28.8 S3: So in this study, they looked at radiation therapy and chemotherapy, I don't believe they looked at immune therapy, but you're right in that the POLE ultra mutated tumors typically have a high tumor mutation burden and immune therapy may be considered at the appropriate time point in the patient's cancer treatment journey. Yeah, I think in this study, they only looked at radiation and chemotherapy, I think they looked at Brachytherapy, external beam radiation, and chemotherapy. Another very interesting study was presented by Dr. Rebecca Previs on comparing the mismatch repair deficiency between primary and metastatic sites of uterine cancers, so in this study, they looked at 32 patients who had mismatch repair deficiency testing both on their primary tumors and the recurrent tumors.
0:24:31.5 S3: And what they found was that six of the 32 patients had mismatch repair deficiency on the primary tumor, and this was retained in the recurrent setting with the same IHC pattern, but in the recurrent tumors, they found nine of 32 patients had mismatch repair deficiency, meaning that there were three additional mismatch repair deficient tumors in the recurrent setting and these patients were mismatch proficient in the primary setting. So this study showed that there's a colonial evolution in these tumors, and this represents a biomarker that has therapeutic implications with immunotherapy options, for example, for these patients, and that we should consider retesting these patients at recurrence. Any questions or thoughts on this one?
0:25:23.0 S2: What were the some of the questions that came up at the meeting after this one about retesting, the primary time of diagnosis and like... When did they stop the testing, I guess, in the evolution of the cancer?
0:25:48.0 S3: So I think Dr. Matthew Powell presented this in his distillation of all of these studies on Endometrial cancer when he said, these recommendations for testing for patients with Endometrial cancer were all outlined in the guidelines, but really we need to see that those guidelines are implemented in clinical practice where there's a gap and that we need to address that gap by making sure that patients are getting this testing done, about the comprehensive genomic tumor profiling as well as this... Consider retesting with mismatch repair deficiency... For mismatch repair deficiency. And so there was... Certainly this was highlighted at the conference that this is something that we need to make sure that these patients are able to get the testing they need to get all of these targeted therapies that have been approved in these spaces.
0:26:43.7 S2: Okay, great. Thanks.
0:26:46.2 S3: Yeah. And the last study I briefly want to touch on is a study on racial disparities in Uterine serous carcinoma that was presented by Dr. Olivia Lara. We know that... Studies have shown that endometrial cancer deaths disproportionately affect black patients and their hypothesis in this study was that genetic and molecular alterations may play important roles in this. So this was a retrospective cohort study of patients with advanced or recurrent endometrial cancer who had received tumor next gen sequencing. The study included 162 patients of which 45 had Uterine serous carcinoma, which is a particularly aggressive subtype of endometrial cancer.
0:27:32.1 S2: Among those patients with this Uterine serous carcinoma, 21 of them were black, which is almost 50%. And what they also showed was that among these patients with Uterine serous carcinoma, CCNE1, which is Cyclin E1 amplification occurred more frequently in black patients than in white patients. And in three black patients, they showed that CCNE1 and ERBB2 were co-amplified. They also showed that among these patients with CCNE1 amplifications, a large proportion, 62.5% of them progressed on first-line platinum. And so the conclusion they drew were that black patients constituted almost 50% of patients with Uterine serous carcinoma, and they had an increased frequency of the CCNE1 amplification. And they called for more research to identify targeted therapies directed towards this CCNE1 amplification while being mindful of the racial differences among these patients with Uterine serous carcinoma. And with that, I will stop sharing and take any questions or toss it back to Shelly.
0:28:51.3 S1: Yeah, that was great Chandrika.
0:28:53.0 S2: That was really good. Yeah.
0:28:55.2 S3: Thank you.
0:28:56.7 S2: Any questions before we switch to The American Society of Breast Surgeons meeting. Okay. So, ASBS was held in Las Vegas this year in April. And the audience is usually composed of breast surgeons, hence the title and Sarah Pass our RMS attended and she's gonna lead a quick review of some of the key talks. Some of them discussing, risk producing, mastectomy and share some interesting case studies that came from that meeting. And we look forward to some discussion. Sarah, all yours.
0:29:40.8 S6: Yeah. Thanks Shelly. Let's share screens... So as Shelly said this conference is mostly covered or attended by breast surgeons, but what was really interesting as I was talking with some of the providers there, they are really also putting an emphasis on making sure that their support staff is also there. So during one of the lunch breaks, they had a really wonderful meeting with APPs, nurses and then some of the support staff where they could all join together and talk about some of the struggles that they deal with in their breast surgery clinics and how they deal with certain cases. I wasn't there since I'm not an APP or a nurse, but from all of the nurses that I talked with, they all had a really great time and said it was really beneficial and so moving forward, they are going to try and encourage some of those providers to join the surgeons so they can be there and have those discussions as well.
0:30:48.6 S6: So the setup for the meeting was actually really interesting. They made it in a pattern that you would have your patients go through, kind of working from screening, imaging, high-risk clinics, surgery, to follow up treatments and clinical trials. It was an interesting way to set up a conference. It was a nice kind of pathway of, here's what you would do first, and then here's what you would do next. There were a bunch of different talks that were there. The two at the top are the two that I'm gonna talk through. But they also spent a ton of time talking through COVID impact on breast cancer care. Since that is really what our lives have been impacted by over the past two and a half years, along with breast imaging, they had a really lovely patient perspective discussion, not just those patients who've had breast cancer, but breast surgeons who've had breast cancer, which was a very different way of looking at it and way it impacts not only their care, but the way that they treat their patients. And then it ended with just a really quick... Rapid fire talk of all of the clinical trials that are open so that the providers would really know.
0:31:57.8 S6: So mitigating disparities in medicine was about an hour long discussion looking at different groups as well as different issues within those groups. So there were a lot of talks about LGBT, persons of color and all of those groups together and what different factors are impacting them. But the talk I'm gonna focus on is one that Dr. Newman... I mean, she was really focusing on why we are having such an issue with finding women... Black women who have more advanced-staged cancer when they seem to be following with the screening guidelines and seem to be showing up. And we're just as good at detecting breast cancer for them. So where are we falling short and making sure that we actually find these women and find those breast cancers at earlier stages when they're more easily treatable and have a better life survival and not as high of a mortality. So she walked through a couple of different studies. They're all referenced down at the bottom of my slide.
0:33:11.9 S6: But showing that we are getting these women in for their mammograms. But we're still finding more advanced age cancer at younger ages and more triple negative than we would normally find in the white population. And while they seem to be showing up and coming in, there are some things that we are missing. They aren't coming in for their serial mammograms, they may be skipping one or two that we don't normally see in the white population. They're having a much longer time between when something is found on their mammogram to actually getting treated and into those offices to take the next steps. And one thing that she really focused on what are these multiple factors that are contributing to these disparities in imaging and getting them into treatment? And some of the largest ones were fear and distrust of the healthcare system.
0:34:06.8 S6: Along with lack of primary care, lack of insurance and under insurance and other barriers, especially in the COVID-19 world that we live in now. And so she was really pushing for the providers that were in the room to really think about how can we get into the community? How can we make them trust us and show that we are there really to help them? Because we do have a history of harming those populations, so how do we get them to trust us? How do we get the education of how important it is to continue to go in for your mammograms? To get these high risk screenings, to follow through with all of these things and really support them in their advocacy work and supporting all of those local leaders and moving forward in that aspect of things.
0:34:48.9 S2: So Sarah, I have a quick question with this, the mammography utilization, was this just looking at the period of COVID or was it taking in pre-COVID, current COVID and then maybe a future study to see outcomes?
0:35:07.4 S6: Yeah. So most of the studies that she was looking at were published in 2018, 2019 and 2020. So they were actually looking at all pre-COVID healthcare, 'cause even if they were published in 2020, they're probably looking at patients care in 2019. So in theory, all of these patients would've been before COVID, the COVID period, except for this last one that was looking at multiple factors, foraging disparities, because that was published in 2021. So it would've been both pre and post-COVID.
0:35:41.3 S2: Okay. And I only ask, because I don't think any of this is new information. I feel like we've heard all of this in other publications and for the factors that are related to it. So I'm curious some of the conversation around it, 'cause I don't think it's all that novel.
0:36:05.0 S6: That was actually something that was interesting about most of the talks at ESPRS, where I felt like I was sitting I was like, "I thought we already knew this information. I thought this was something we all had agreed on was a problem. Or these were all barriers that we'd all discussed before." But I think the reason that they're re-bringing this up is just as a reminder, like this is something that is still a problem. While we already know a lot of this information, it's all stuff we've already talked about, probably ad nauseam, this is still a problem, and this is still something that we need to keep addressing. We need to continue to go into the community and talk and educate and advocate for these patients and bring them in because while we all know the barriers, and we all know the lower... The higher mortality rate for these women and the fact that they have more aggressive cancer and often at much younger ages, we're still not getting them in for their screening.
0:37:00.9 S2: Yeah. So we may know it, but we haven't actually done anything to make changes, to it. And probably COVID is only exacerbating these disparities.
0:37:09.0 S6: Absolutely. Any other questions about this talk? Okay. The last one that I'm gonna focus on was the high risk clinical practice talk. And again, there were a lot of talks in this. And it's what Shelly mentioned before, these are all things we knew, it started off with a review of all of the risk assessment models that are out there, Tyrer-Cuzick, Gail, BOADICEA, BRCAPRO, just reviewing the limitations and benefits of each of those, we talked through really some basic information that I kind of just assumed that everyone knew at that point. When do you use Tamoxifen? What are the benefits of diet and exercise? Things that I felt like we already knew. But one thing that I really took away from this talk that was really interesting was Dr. Tuttle's talk of when do we actually need to be recommending or discussing risk reducing mastectomies?
0:38:18.1 S6: And he did it in a really interesting way that I really appreciated. He didn't just walk through the risks and benefits, when, how do you talk about if they're seeking advice versus actually really wanting the surgery, the different factors that go with it, but he encased them in cases throughout his entire talk. And it was really interesting to see how breast surgeons really looked at each of these cases and how they would've discussed these with patients that came into their office. And every single time he went through the case, he would start with based on this case and what we know right now, would you recommend or be more, "I don't really care, you can do what you want." Or really discourage a patient from going through risk reducing mastectomy. And these are just two of the many cases that he presented.
0:39:02.3 S6: But it was interesting, the focus that he had on all of these. So the first case I'm gonna talk about is a 40-year-old healthy woman with LCIS. She received genetic testing of VUS and BRCA2 which we all know is not a pathogenic mutation you would follow them based on family history, which she doesn't really have, at least in the breast cancer space. But the patient was asking for advice, and should they have a risk reducing mastectomy? And what's... The group all agreed that they would probably dissuade her or be more on the meh side of things of whether or not they would push a risk reducing mastectomy, but what he really focused on was one reminder that a VUS is not a pathogenic mutation, just that constant reminder within that space between...
0:39:52.9 S6: Last year when I think they talked about that again. And here and now, just to make sure that it's really reverberating through the community. Because that's a piece of misinformation we don't want sticking. But also you need to talk to the patient and have her tell you why is she asking about this? Is it because she's heard about BRCA2 and doesn't fully understand that a VUS isn't pathogenic. Does she need better education on what LCIS is? Have I not, I as a breast surgeon not done a good job to explain what that diagnosis means? Or is she just asking because that's one of the many things that she's read online? And so really talking with the patient of, "Why are you asking this?" So that I can make sure to give you the informations that you feel empowered to make a choice in the... And then the second case was a 62-year-old BRCA positive patient who had just recently tested positive, had a total hysterectomy and bilateral salpingo-oophorectomy 10 years ago at 52. No medical problems. Multiple negative breast imaging. But she was coming in, wanting a risk-reducing mastectomy, mainly because we assumed because of her sister who was diagnosed with breast cancer at 52. And so this group was actually fairly discouraging.
0:41:07.0 S6: They were leaning towards telling her, "You've made it to 62 without breast cancer. You've already had your ovaries out. And assuming that was done pre-menopausally, that could reduce your risk for breast cancer. There isn't a huge reason that we would want to encourage a risk-reducing mastectomy." But what I thought was really nice was Dr. Tuttle reminded them that, "While you have an opinion going into this case, the patient came in saying, "I want this surgery, because I've watched my sister deal with this breast cancer diagnosis. I have a BRCA1 mutation." And if she's 62, you have to take into account what are the comorbidities? What are the other health issues? What does this surgery really impact for her? But if she's healthy, the surgery is something that can be done for her. And this is something she wants. It can reduce the anxiety and other concerns for her and make her quality of life better. Because we're removing that constant screening. And she wants the surgery, then that's something that we should be supporting her in." So it was very interesting to see that discussion throughout the group both, and that changing mindset of, "While I have an opinion going into this case, I need to take the patient in front of me into account as well."
0:42:24.0 S2: I think that's a great point. I think both of these cases bring up two very important issues in... With the first case, there was the paper from, I think Allison Kurian in 2017 or something in that ballpark, where they talked about how surgeons that had less experience with genetics would do a risk-reducing mastectomy for a VUS. And I felt like that paper was interesting. But I feel the piece that potentially could be missed is what is presented in case two, is what that patient is coming in the door with, some of their information that might be accurate, not accurate, the psychological burden that they're bringing in, or whom they know that has had a diagnosis, that they just don't wanna deal with it. So I feel like sometimes the literature misses that human piece that you can't all put together with statistics and figures. But I'd be curious of anybody else that has some perspectives on this.
0:43:32.9 S1: Yeah, no. I'll add to that. So from my experience, there also seems to be like a wide spectrum of how providers flavor this too, because... And think about it. Because some are, yes, very easy to... They'll say, "Yeah, I recommend a risk-reducing mastectomy." They won't even say like consider. That's like the far end, like 100% recommending. And then there's a lot of people that practice a little bit more, what I would say, like kinda guideline, NCCN-driven, which is like, "Yeah, you can consider this." And then I've seen even the far end of the other spectrum, which is, "This is like mutilation of healthy tissue," really trying to talk people out of risk-reducing mastectomies at all costs. And they'll certainly flavor those patient discussions. And it is interesting that the guidelines, for the most part say the same thing. And you have such a wide range of how people approach this.
0:44:37.4 S6: Yeah, absolutely. And it was interesting that... This was the only talk where they really even brought up genetics at all throughout the whole conference. So it was interesting just to see their reaction of how do they interpret all of these guidelines and what are they reading and how much do they know and what are they taking to account from those genetic results when they're meeting with these patients as well.
0:44:58.6 S1: Yeah, and Robin Palmer has... Certainly, she put in the chat about what about discussions of insurance reimbursement for risk-reducing mastectomy? Am I off-base in thinking that providers can code so that insurance is likely to reimburse regardless of whether a risk-reducing mastectomy is really medically indicated? Yeah, that's a great question. I don't know if we have anyone on the line that has a particular experience there, if we have any breast surgeons on the line that wanna chime in on their experience. Yeah, I'm not too sure. I've worked a few different places. I haven't seen any young, major barriers, or at least for mutation carriers or individuals that are young with their first breast cancer to have both breasts removed. But yeah, obviously, these are all gonna be where you live, what insurance you have, geography. All those things come into play.
0:46:00.5 S4: Obviously, I'm not a breast surgeon, this is Lauren, but I've had conversations as it relates to moderately penetrant genes and getting that covered, getting risk-reducing mastectomies or contralateral covered, and it's interesting because the insurance companies per the conversations I've had with some of the breast surgeons, I work with, they don't discriminate between BRCA1 or PALB2 or CHEK2, they just see a patient is pathogenic variant or mutation positive, and they don't really look further into it, so it's interesting, kind of, will they deny coverage? Probably not, but it's interesting if they're mutation negative or if they have a VUS, are there other factors or other risk models? Obviously Tyrer-Cuzick, other things that you can use, and is the physician's clinical judgment of the patient being coded as high risk enough for them to cover? I don't know, it's a good question, though.
0:47:04.4 S2: So in the interest of time, I think we're gonna move on to the last one, but thank you very much for the discussions, I think we can go on and on with this one. The last meeting that we're gonna review is the 39th annual Miami Breast Conference, which was a hybrid meeting, it was held in the worst location, which is the Fontainebleau, Miami, Florida. I'm sure we all want to go there next year. And the audience is medical, surgical, radiation oncologists, and Christina Flanigan, our RMS is going to share a couple highlights from this meeting.
0:47:43.6 S7: Okay, thank you, Shelly. Thank you everyone. So I'll go ahead and get started. Some of what I'm going through early on are just the reiteration of some of the background that Shelly provided. So this is the 39th annual Miami Breast Cancer Conference. The dates for this conference were March 3 through 6 of 2022, and this was up at Fontainebleau Hotel and Conference Center in Miami Beach. The conference was a hybrid model, which included both virtual and in-person attendance, the primary audience are medical, surgical and radiation oncologists, there is also a secondary target audience according to this group of fellows, MPs, PAs, and other health care professionals. The themes, of course, there is a key focus on breast cancer at the Miami Breast Cancer Conference, with special attention to adaptive and personalized therapies, these particularly include developments and immunotherapy, newer targeted agents such as selective estrogen receptor downregulators, PARP inhibitors and antibody drug conjugates, so I'll speak to some of these coming up. Additional themes were surgical techniques, there was a lot of content on harm reduction and over-treatment, so can we forgo different types of potentially risky interventions such as surgeries, chemotherapy etcetera.
0:49:23.6 S7: There were also case reports reviewed and there was some hereditary cancer discussion, but it was fairly light on hereditary cancer and for the genetics audience, it seemed to be really core topics such as male breast cancer and BRCA, etcetera. Okay, so for key takeaways in the early stage breast cancer setting, there was much discussion on ovarian suppression, some background includes that there's growing evidence suggesting that ovarian suppression is important for pre-menopausal patients with early stage hormones that are positive for genetic breast cancer. And updates provided from the text and soft slides showed between a 3% to 5% reduction in distant disease-free recurrence in high-risk patients, and some of the discussion included what would be the best way for us to achieve or attempt immune suppression, including whether or not we should use Depa-gonadotropin analogues in this setting. In the advanced breast cancer setting, there was a significant focus on selective estrogen receptor downregulators or SERDs, so this was interesting because exposure to estrogen suppressing therapy with agents such as aromatase inhibitors can result in the development of estrogen receptor mutation, so adaptive mutations.
0:50:58.9 S7: And this ESR1 gene that codes for the estrogen receptor can be mutated in about 30 to 40% of patients that have been exposed to aromatase inhibitor therapy and have progressed on such therapy. And SERDs may successfully down-regulate even mutant forms of the estrogen receptor, so EMERALD 3, which was first presented at San Antonio Breast Cancer Symposium showed a clear advantage of elacestrant over fulvestrant in previously treated ER positive advanced breast cancers. And the discussion included that we have much more to learn about SERDs, including how they might interact with therapies that we use earlier on in treatments, for example, on the first line and how they combine with other agents. This is a little bit of a closer look at Emerald 3. So overall, SERDs, which were given orally lead to a 30% reduction in the risk of disease progression or death compared with standard of careful elacestrant, which makes elacestrant the first agent demonstrated statistically significant and clinically meaningful improvement in progression-free survival in this space.
0:52:12.4 S7: And of the two populations of the trial, the overall population, and specifically ESR1 mutated population, in the overall population, the SERD agent, elacestrant reduced risk of progression or death by 32% compared to a reduction of disease progression or death by 50% on the ESR1 mutation population. So this was really exciting in a secondary endpoint, which is overall survival is still a little new, but results are expected later on this year or early next year.
0:52:53.4 S7: To continue in the HER2-positive space, there was a focus on anti-neoplastic antibody drug conjugates, and the two trials covered were DESTINY-03 and DESTINY-04. DESTINY-03 showed a clear superiority of Trastuzumab deruxtecan over T-DM1, this is an HER2 drug combination, and there was discussion of this potentially moving to be preferred agent and second line therapy for these patients. And DESTINY-04 showed Trastuzumab deruxtecan was superior in comparison to physician choice chemotherapy, particularly in breast cancers that are HER2-low expressing. So I'll go into this in little greater detail here. And progression-free survival at 12 months was 75.8% with the drug compared to 34.1% with Trastuzumab emtansine, I'm so sorry about my pronunciation, and an overall response occurred in 79.7% of patients compared to 34.2% of patients. And those are the main highlights that I have for Miami Breast, any questions? I see that we have about three minutes left.
0:54:27.3 S2: Very good. Christina, I'm curious how well was the attendance?
0:54:32.4 S7: It was fairly lightly attended compared to the last time. I'm sorry about this. The last time I attended before the pandemic. The last conference before the pandemic was actually in March of 2020, which you would think might have been poorly attended given timing, but it actually felt much better attended than this particular meeting.
0:55:04.7 S2: The other conference that we aren't going to go into today, was the one that just happened this weekend at this University of Chicago City of Hope conference, that they flip-flop locations each year. It's an excellent conference, two and a half day conference. CGA gave a segment on hereditary colon cancer, it really draws some of the key individuals in the genetics world from Mark Robson, TJ used to be a part of it, Jane Chatfield, Laura Esserman, Steven Narod, I think I mentioned Bader Gary talks about prostate cancer. So it's an excellent overall from head to toe overview of hereditary. And some of the things that are coming, they had a great session on AI, which will be really interesting in the next several years to see how artificial intelligence will really impact patient screening and care. So if you ever have an opportunity to attend that, whether it's in Chicago or then Duarte, California, I highly recommend it. I'm gonna pass this over to TJ to close this out.
0:56:24.9 S1: Yeah, no, thanks everybody. Christina, Chandrika, Sarah, great presentations. I can't thank you enough. Thanks Shelly, for organizing all of this. Join us, when have our next meeting. Oop, I lost it. It's coming up in a couple of weeks, we'll come back with mental health genomics, so don't forget that. Put it on your calendar, you can pre-register if you go to a Myriad Live or you could just Google Myriad Live and then you'll find all the upcoming topics and then we'll add more into June and July pretty soon. So I appreciate everyone coming on and yeah, great learning today, we went through a lot of content and information. So yeah, it looks like very positive comments [chuckle] about all the information covered, so thanks everyone, and we'll probably have to do another one of these maybe at some point after ASCA and jeez, we have Fall. So always good to review what's hot going on at some of these conferences. So have a good rest of your day.