Highlights from the 2021 San Antonio Breast Cancer Symposium, with Virginia Kaklamani, MD, DSc

This year’s annual San Antonio Breast Cancer Symposium (SABCS) was a hybrid gathering of researchers, doctors, and advocates coming together both virtually and in-person to talk about important and exciting news in breast cancer research.

Living Beyond Breast Cancer CEO Jean A. Sachs, MSS, MLSP, spoke with Virginia Kaklamani, MD, DSc, professor of medicine at the University of Texas Health Sciences Center and co-director of SABCS, about the major findings presented at the symposium and what they mean for you. Catch up with the rest of our coverage.

• Olaparib well tolerated in people with early-stage BRCA+, HER2- disease
• T-DXd emerges as new standard second-line treatment for HER2+ MBC
• Elacestrant improves outcomes for ER+ metastatic breast cancer

 

Jean A. Sachs, MSS, MLSP (00:07):

Hi everybody. I'm Jean Sachs. I'm the CEO of Living Beyond Breast Cancer and today we will be talking about the 2021 San Antonio Breast Cancer Symposium, which for anyone in the breast cancer world this is the most important global meeting and often provides practice-changing information. It really brings the best minds together. It also brings together advocates from all over the world and it's a very exciting meeting. Today we are extremely fortunate to have Dr. Virginia Kaklamani. She was one of the co-directors of the 2021 symposium, which I'm sure was a really challenging job this year, but in her day job, she is the professor of medicine at the division of hematology and oncology at the University of Texas Health and Sciences in San Antonio. So at least you didn't have to travel, right?

Virginia Kaklamani, MD, DSc (01:08):
I did not. That is a good thing.

Jean A. Sachs, MSS, MLSP (01:09):
That is a positive thing. So, to read her full bio, which is very impressive, please go to our website, lbbc.org. Welcome Dr. Kaklamani, and I'm sure you're tired so thank you for making time for Living Beyond Breast Cancer.

Virginia Kaklamani, MD, DSc (01:25):
Thank you, Jean. Thanks for having me.

Jean A. Sachs, MSS, MLSP (01:27):
So why don't we just start off with what I know our community wants to know most, which was what were the highlights for you from this very big meeting?

Virginia Kaklamani, MD, DSc (01:38):
I think kind of the biggest theme that has been emerging in the past few years is how do we individualize our treatment to the specific patient and the specific time during their therapy? So, for example, we know that cancers evolve over time. And so, if we do a biopsy at the initial diagnosis, that cancer does not stay the same for the next 5, 10, 15 years. What we're learning,, and what we did this year more with these clinical trials that were presented, was monitoring the cancer throughout its course and seeing how it changes and adjusting our therapies based on those changes. And one of the trials that did that, the PALLAS trial in patients with metastatic estrogen-positive breast cancer, they looked at these mutations in the estrogen receptor, they're called ESR1 mutations, and they took blood because now we're lucky enough to not have to do biopsies anymore. We can do circulating tumor DNA from blood draws. They monitored these mutations over time and what they were able to show was that that patients on specific treatment, their cancers start to gain these mutations, and at some point when they were gaining these mutations, that's how those drugs weren't working anymore. And before we could clinically see that those drugs were not working, they were changing therapy to another therapy that bypasses in some way that estrogen receptor and those patients actually did better. They were able to stay on that other therapy a little bit longer than if we had kept them on the previous therapy waiting their scans to show that the cancer was growing. And I think this is what we're seeing more and more that we're monitoring the cancer in real time, in a specific patient, not in, you know, 5,000 other patients that were on clinical trials 10 years ago, and being able with this way to predict, or to change our treatment and improve the patient outcomes.

Jean A. Sachs, MSS, MLSP (03:41):
It's amazing. So, it's really becoming even more personalized than just your subtype. It's the genomics, it's everything, right?

Virginia Kaklamani, MD, DSc (03:50):
Exactly. And how it's evolving, and how different cancers evolve at a different pace. And it's important that we capture that.

Virginia Kaklamani, MD, DSc  (03:58):
It’s unbelievable. So, tell us about … I know there was a fair amount of news for the triple negative breast cancer. What were your big takeaways?

Virginia Kaklamani, MD, DSc (04:10):
For triple negative breast cancer, if we talk about the early-stage breast cancer there were a few important updates. First of all, the use of immunotherapy now for women at a high enough risk is considered standard of care. And there was some data presented at the San Antonio symposium, again, showing that immunotherapy is very important. It can have its toxicities, but it improves outcomes. We also had a study looking at again monitoring changes, mutations in the cancer and being able to switch our therapies around and finding out that if a mutation has a drug that works for that mutation and we give that drug to the patient, then we, again, we can improve that patient's outcomes. In the metastatic setting, again, there were some clinical trials on immunotherapy showing that for a specific subtype of triple negative breast cancer immunotherapies, again, very important. And then there was a new drug, it was an antibody drug conjugate that seemed to be active in triple negative breast cancer, obviously that was an early-stage trial. There's gonna be more trials going on, but we're gonna have more antibody, drug conjugates available for us to treat triple negative breast cancer.

Jean A. Sachs, MSS, MLSP (05:26):
Right. So, does that mean they're finding some targets? I know triple negative always feels like such a hard diagnosis. So, does this mean we're gonna find some targets?

Virginia Kaklamani, MD, DSc (05:38):
We have some targets and it's interesting. Somebody made the point that we should really not call it triple negative anymore. This is just a bad name, right? Because, as you alluded to, it just means that it's just bad. There's nothing to do for it. Right? And there is. What we're finding out, there's two kinds of targets. One is a target where that protein is bad and it tends to be present on these cancers, and by killing that protein, we can kill the cancer. Another kind of target that we're starting to use more and more is where that protein is just present. It's not bad, it's not good. It's just there. And by being there retargeted, and then you are able to identify those cancer cells, you can kill selectively those cancer cells without killing the nearby normal cells. Then you can also get a benefit. So those are this new approach where we're able to identify a protein that's present in triple negative breast cancer. It's not really present in other normal cells, and so we can target that protein, kill the cancer cells, improve outcomes for triple negative breast cancer patients. There's also this new term that's emerging that's called HER2low. HER2low is where … these are not HER2+ breast cancers, but they do have a little bit of expression of the HER2. And again, the same concept, HER2 is there. It may not act as, as a bad guy, but it's there. And so, if you target HER2 again, you can kill those triple negative breast cancer cells that express it a little bit without having to kill the normal cells.

Jean A. Sachs, MSS, MLSP (07:20):
Right. So interesting. I've certainly talked, spoken over the years with a lot of women who are HER2low, and it's a hard diagnosis because it seems to become triple negative. So, can you tell us about this new delivery mechanism, which is called the Trojan-horse delivery and how that works? And I know it was being used in HER2+, but now are we thinking this is possible with triple negative as well?

Virginia Kaklamani, MD, DSc (07:47):
Absolutely. So, since I'm Greek, I love the Trojan horse analogy because that's how we beat the Trojans. Right? So Trojan horse, what is it? You have a little horse, and everyone thinks is a good guy and so it goes into the fort and all of a sudden the soldiers come out and kill the city. And this is exactly what we do with these antibody drug conjugates. It's an antibody, it has a little linker and a drug. The drug is too toxic to just give it by itself and so we use the approach of the antibody. The antibody goes to whatever the protein is that we target, and it binds onto the cell. The cell sees the antibody says, well, you know, I don't like it on my surface, I just wanna kill it. And so, it internalizes it, it brings it inside the cell. Once it brings it inside the cell because the cell hasn't figured it out that it has a toxin, the toxin gets released into the cell and then the toxin goes to the nucleus, and it kills the cell. Sometimes it can actually go back out and kill some of the nearby cancer cells, which is also good. This is an approach that we've had for HER2+ breast cancer and in the past year we've had a nice approval in triple-negative breast cancer and then more drugs at the symposium showing that they can also be active in that approach. Again, the benefit of these drugs is that they don't have a lot of toxicity because they are more targeting the cancer than anything else. And they have really good efficacy as well.

Jean A. Sachs, MSS, MLSP (09:19):
Right. So, we should look for potential more approvals in this area. Right?

Virginia Kaklamani, MD, DSc (09:23):
Absolutely. Absolutely.

Jean A. Sachs, MSS, MLSP (09:26):
So, what were the interesting studies for you that were presented for people living with metastatic, particularly the ER+.

Virginia Kaklamani, MD, DSc (09:36):
So, ER+ metastatic breast cancer the one drug that I think we're gonna be looking at more and more is called elacestrant.

Editor’s note: On January 30, 2023, elacestrant (Orserdu) was FDA-approved to treat hormone receptor-positive, HER2-negative advanced or metastatic breast cancer that has tested positive for an ESR1 mutation with disease progression following treatment with at least one hormonal therapy. Read more about elacestrant.

Jean A. Sachs, MSS, MLSP (09:44):
Thank you for pronouncing that.

Virginia Kaklamani, MD, DSc (09:46):
Well, I was one of the initial primary investigators, not just for the trial, but for the phase I trials of that drug so I had to learn it. We used to call it RAD1901 and that was so much easier.

Jean A. Sachs, MSS, MLSP (10:00):
So much easier.

Virginia Kaklamani, MD, DSc (10:01): This is a drug that is similar to fulvestrant, which is a selective estrogen receptor downregulator. It basically means that it goes to the estrogen receptor and destroys it. The ER, unfortunately, regenerates, so that's why we need to keep giving the drug. But anyway, fulvestrant, as you all know, is an intramuscular injection. That means that women have to come to the office and have two injections, one butt cheek, the other butt cheek. And because we can't really inject a lot of stuff into the butt the limitation for fulvestrant has always been the dose. We all think based on animal studies that if we were able to give a higher dose of fulvestrant we would actually get an even more effective drug, but we cannot. So, these oral fulvestrant analogs are now coming out and there's 10, 15 of them. There's a lot of clinical trials even in the early stage setting now, but this is the first large phase III trial that was presented with elacestrant. So now they're looking at whether they can improve outcomes compared to other medications, including fulvestrant. Elacestrant was able to show that it was a superior estrogen therapy. So based on all of the data that we have from other trials in this trial called the EMERALD trial, it showed that elacestrant is probably our most active antiestrogen therapy. It was better than the aromatase inhibitors and it was better than fulvestrant. Having said that, there’s always good and then a little bit of bad, right? Women on both arms of the trial really did not do very well. We had women on the control arm, which was either the aromatase inhibitor or the fulvestrant, and they were able to stay on the drug before the cancer grew for less than two months. The women on the elacestrant were able to stay for around three months, so that's not good. And this is where we have an opportunity to identify who those women are, that really those drugs are not gonna work well and figure out what will. For the women where we could see a response initially or stable disease, those women did well for quite some time and significantly better with elacestrant, but the overall population, there was a subset of women that we need to do a lot more work on. But this was probably the highlight for ER+ disease.

Jean A. Sachs, MSS, MLSP (12:29):
Right. And this was the EMERALD trial, right? If people want to look it up and read more. Okay. So good news for some, I think this is what we're learning in breast cancer, right? Like headway for some, but we have to keep getting those that the drug doesn't work as well. Okay. So, what about early stage? I know we talked about it a little bit, but there were some significant report outs on trials seeking to prevent recurrence and additional data on who should actually receive chemotherapy. So, what stood out for you?

Virginia Kaklamani, MD, DSc (13:03):
The data that has come out about recurrences is data on the use of CDK4/6 inhibitors. And these are drugs that we've had now in the metastatic setting since 2015, they have been really important drugs in how we treat estrogen positive metastatic breast cancer. Now reports are showing that these drugs are also active in the early stage setting. Again, headways. These drugs can have toxicities like everything that we give, but headways as to how to treat early-stage breast cancer. Now, whenever we try to increase treatment, we also try to think of the women that may not need as much treatment so that we can optimize treatment for all. What we looked at was a clinical trial that was at last year at this meeting, the RXponder trial, which looked at trying to avoid chemotherapy for women that have early-stage estrogen, positive lymph node, positive breast cancer.

Virginia Kaklamani, MD, DSc (14:08):
And we were always afraid to not give chemotherapy to these women cause we thought they had a high risk, but we also figured that some of these women probably won't benefit from chemotherapy. There was another update on this clinical trial suggesting that women that are postmenopausal that have a specific molecular test called Oncotype DX [with a] score of 0 to 25, those women won't benefit from chemotherapy. And that's a large number of those patients. So great news for those women that we can avoid chemotherapy. For the younger women, the premenopausal women, the data still shows that we need chemotherapy. There was a lot of debate as to why do we need chemotherapy. And there was actually a debate about this that I would urge your viewers to look at because it was wonderful with two experts arguing whether the benefit of chemotherapy is making women postmenopausal, so blocking their ovaries, or the benefit of chemotherapy is just the benefit of chemotherapy, kills cancer cells.

Jean A. Sachs, MSS, MLSP (15:05):
Wow. That's interesting.

Virginia Kaklamani, MD, DSc (15:07):
And nobody really knows. That were a debate for a good reason that were still debating. But I, I think some of these younger women may not need the chemotherapy and probably just suppressing their ovaries is enough, but there is still in my mind a benefit for chemotherapy beyond suppressing the ovaries. And so that's something that we're still gonna be arguing and hopefully have a clinical trial at some point that addresses that.

Jean A. Sachs, MSS, MLSP (15:35):
For the postmenopausal women though, who have a score below 25, the data is really seems to be very clear.

Virginia Kaklamani, MD, DSc (15:44):
Very clear: no benefit from chemotherapy.

Jean A. Sachs, MSS, MLSP (15:47):
Okay. And so always for the younger women, they are always in a tough position. I mean, I never wanna minimize early menopause. That’s rough.

Virginia Kaklamani, MD, DSc (15:57):
Exactly. And you know, our patients know this significantly better than we do. When we talk about chemotherapy, chemotherapy is three months and it's not benign by any means. It causes a lot of toxicities, but you give it for three months and you're done. If you wanna suppress somebody's ovaries, you have to do it for at least five years and you have to be consistent, and that woman has to understand that going into menopause at the age of 35 or 40 for 5 years is something she's gonna have to do. And so, I have a lot of patients that if you kind of talk to them and they realize what's going on, or patients that have gotten the chemotherapy and then are supposed to get the ovarian suppression, they'll say, I'd rather get the chemo. It's three months and I'm done because otherwise I have to go through five years of suppressing my ovaries and do I really wanna do that? So, it's kind of, it’s everything has its own potential side effects, and it's important that we explain to our patients exactly what this entails because it's not easy to go into early menopause at the age of, you know, 35 or 40.

Jean A. Sachs, MSS, MLSP (17:01):
No, it's not. Well, we will find where that debate is, and we'll make sure to link it because I think it's important for our audience to be educated. And, of course, it's hard when you're diagnosed breast cancer and you have a choice, you know, it's a good thing and a really hard thing for women, you know? So, I know you have to present those options. So, anything else on early-stage that you wanna touch on?

Virginia Kaklamani, MD, DSc (17:28):
Early-stage breast cancer, again, we looked a little bit at how so circulating tumor DNA changes a woman's prognosis. There were actually some questions from advocates at one of our programs saying, well, if we have that information, why are we not using it? Why are you not telling us that we have a high risk of our cancer coming back? And the answer is because we don't know what to do about it. And I'm not gonna tell someone that their cancer has a high risk of coming back because I'm checking something and it's going up and up and up and up when I can't present to them, and this is what we should do. This is where we're at now. We're identifying women that have a high risk of their cancer coming back before even that is shown on scans. But now we need to figure out how can we address this? How can we prevent their cancer from coming back? And what one of the studies interestingly showed was that when you saw that number of these the circulating tumor DNA going up, and then when they did the scans, those patients already had cancer in another part of their bodies in those scans, which means that we may have missed it the first time around. We may have not done scans that we should have done to pick up that cancer. But ultimately, whenever you pick up that cancer the ultimate goal is to help that woman live longer. And we haven't gotten there yet, which is why you see physicians being reluctant to use these very modern techniques, because we don't wanna use something just because it's there. We wanna use it because it's useful for the patients,

Jean A. Sachs, MSS, MLSP (19:08):
Right? So, this is a good, good moment for you to give a plug for clinical trials and that you gotta pay it forward to help the next person behind you. Right?

Virginia Kaklamani, MD, DSc (19:18):
So important. And there are studies that have shown that women that participate in clinical trials actually have better outcomes. So yes, you do have to pay it forward. The drugs that you are taking are drugs because other women participated in trials that showed that they're superior to something else, but also you have the opportunity to improve your outcomes because you're participating in clinical trials. So that's again important for both of these things to remember, because it's not easy to participate in clinical trials, you have to jump through a lot of hoops. You have to sign consent forms over and over again. You probably have to come for more visits. You probably have to have more blood draws. You may have to have a biopsy that you otherwise didn't have, but unless you go through this we won't know how to best treat you.

Jean A. Sachs, MSS, MLSP (20:09):
Right. And certainly, with breast cancer where we said it's becoming so individualized, the more you very, very smart people can help advance this. So, let's move to … we were pleased to see that health disparities were once again, really at the center stage and a part of a lot of discussion. And, you know, what is your feeling? Is this here to stay? Are we ready to really tackle this issue? And I see that Dr. Olufunmilayo Olopade spoke so eloquently about, you know, not just within America, but within the world addressing these health disparities.

Virginia Kaklamani, MD, DSc (20:50):
I sure hope that we can make progress, because otherwise, what are we doing? You know the health disparities; what we've realized initially we were blaming genetics. You know, it's genetics. These, you know, black women just have bad genes that predispose them to getting bad cancers, and there's nothing we can do about it. And now we're realizing that might be a small part of it, but that's not only it. And the same way as America and the rest of the world has disparities in not just breast cancer, but every fact of life, we have these disparities in breast cancer, and we need to deal with them because that's the only way we're going to improve outcomes in those women. And eventually we're gonna help our healthcare system. So, by helping our healthcare system, we're gonna help ourselves. This is not, and we've seen this with COVID, right? We're not one nation. If America's doing great, but you know, Canada is not, or Mexico is not, COVID is gonna come to the U.S. The same thing with breast cancer, same thing with every other disease. This was an important part of our symposium this year and it's gonna be an important part of the future symposia as well.

Jean A. Sachs, MSS, MLSP (22:05):
That's good to hear. And I, I think that role of the advocates is so important. And I know, so just to end, what was it like being there in person? And did you feel the energy from the advocates or not? Having all your colleagues together …  give us a sense of what it was like.

Virginia Kaklamani, MD, DSc (22:25):
It was quieter than usual, but the people that were there were so energized when, you know, when we first came into the symposium, they actually had the red carpet for us, and they had a band playing music and they had people serving these non-alcoholic beverages that looked like champagne. And all of the San Antonio community were actually there and clapping and saying, thank you for being here. And everybody was so excited to be at a live conference for once after two years. It was also nice because you could get to see your colleagues, otherwise it's so crowded you don't get to see anyone. The advocates were there, and they had a huge voice, which, which is wonderful. We all do this for them. Right?  And if we're not doing a good job, we better hear it from them. So, it was a regardless of the fewer people that attended the energy was right there. The disparity session that was run by Dr. Charles Perou and Tiger Lily was also a wonderful session. I think it went really well highlighting what we can do better. So overall it was, it was a great symposium, I think.

Jean A. Sachs, MSS, MLSP (23:36):
I really appreciate you sharing that because, you know, it's so hard for those of us that have traveled there in December for so many years so many doctors and advocates, and, you know, not to be there now for another year and really missing the connection. I know for Living Beyond Breast Cancer many of our Hear My Voice advocates are metastatic advocates. They went, I mean, they were like, we're gonna be there. And, and how much they put this in the center, you know, we’re gonna be there, we're gonna make our voices heard.

Virginia Kaklamani, MD, DSc (24:07):
Everybody was wearing masks. We could not mandate vaccination for certain political reasons, but everybody was wearing a mask. Everybody was social distancing because we only had 2,500 people so it was very easy to social distance. But also, it was so wonderful at point it hit me, there was this session that we were doing, and it was a review of case presentations. And we had three people on the panel, and we had four people on the little Zoom windows. One was an advocate from our, the south, I wanna say North Carolina, another one was a pathologist from France, another one was a radiation oncologist from Australia, and then there was a fourth person who I can't remember where they were from. And so, you're seeing the people in San Antonio talking to the person in Australia where it's the next day, the next morning, right? Talking to the to the person from France, where it's at night and, and the advocate from North Carolina and this was so global and it just hit me that this is what it is, and these hybrids symposia just bring everybody together. And everybody has a voice and, and it was just absolutely wonderful to see.

Jean A. Sachs, MSS, MLSP (25:24):
It's so amazing. I mean, I guess there was some positive things out of this pandemic. We've certainly figured out how to use technology to build community. Well, I just wanna thank you personally, for all you do for the breast cancer community, how open you are to the advocates and your support of Living Beyond Breast Cancer. We are so lucky to have you in the breast cancer medical oncology world. So, thank you so much.

Virginia Kaklamani, MD, DSc: 
Thank you.

Jean A. Sachs, MSS, MLSP:
And for everyone watching, we'll make sure that we provide links on the website. All the sessions, I think almost all the sessions, are available via livestream. So can take your time. I, I kind of enjoy that you take notes, go back and listen again, learn how to pronounce those drug names so that when you go to your doctor you can tell them what it is. So, visit our website at lbbc.org. We have some stories written about some of the topics that Dr. Kaklamani discussed. And for those of you in need of peer support, remember log onto lbc.org. we can match you with a helpline volunteer. You can also join one of our closed Facebook communities. So, we are here for you and wishing you all happy and healthy 20,22 let's hope. It's really different.

Virginia Kaklamani, MD, DSc: 
Yes.