Medical updates in MBC: What you need to know

Transcript

Eleonora Teplinsky, MD [00:00:08]

Today I was asked to give a talk on medical updates in metastatic breast cancer, and some of that is a what Dr. Kaklamani went over. But I think the more we hear things, for me at least, the more I hear it, the more I learn from it. So I think if there’s a little bit of overlap, hopefully you’ll find that helpful.

I’m going to go into some of the trials and some of the side effects from some of the newer medicine. And I think whenever we talk about updates, we break it down into hormone receptor-positive, HER2-positive, and triple-negative. Depending on what subtype and what type of MBC you are living with, your family, your loved one is living with, sometimes there’s more data for one versus the other, and it can feel sometimes almost isolating. Like why is there not enough right now for HER2? Or why is there more for hormone receptor positive?

But the research really ebbs and flows. And a couple of years ago we had this overwhelming amount of data for HER2 positive, and now we’re seeing a little bit more for hormone receptor positive and triple-negative. It really does ebb and flow and so just keep that in mind. I’m not talking about everything in MBC, but just some of the recent updates in the last year or so.

I will say, I gave part of this talk in September and even in the last 6 months I had to change half the slides. So that’s the pace that things are evolving.

There should be plenty of time for questions, so make sure you send them in, and I’ll do my very best to answer as many as we can. Those are my disclosures.

We’re going to talk about today is that current landscape, some of the newer medicines, novel endocrine therapies, antibody-drug conjugates, PI3K inhibitors, and more. So we’re going to get into all of that.

What is metastatic breast cancer? Metastatic breast cancer is breast cancer that has spread outside of the breast and the axillary lymph nodes. And it has gone to other parts of our body. It could be the bones, it could be the lymph nodes on the other side and the other breast. It can be the lungs, the brain, so anything. That’s going to be that category of metastatic breast cancer.

Metastatic breast cancer that is stage IV upon presentation. Some of you in this room may have been diagnosed with de novo breast cancer. So at the time of presentation, you were found to be stage IV. That’s going to be called stage IV or de novo. We really use the term metastatic to mean someone that was stage I through III initially and then developed metastatic disease. These are semantics, it doesn’t change much, but that’s why you can hear the differences in some of the language.

One of the things that we’re seeing actually is that metastatic recurrences are decreasing. So due to more therapies in the adjuvant setting like CDK 4/6 inhibitors, immunotherapy, less people are being diagnosed with recurrence. But we’re actually seeing, and we don’t really know why that is, more people being diagnosed with de novo or stage IV MBC at time of presentation. There’s obviously a lot more work that needs to be done to figure out why that’s happening and how we can reduce that rate. And a lot of that is differences to those exposures to prior systemic therapy.

One of the things before we talk about updates, I’m not going to talk too much here about ductile versus lobular. Does anyone have lobular metastatic in this room? A lot of lobular.

The two big things about lobular is lobular metastatic breast cancer tends to present in different parts of the body. We see less in the lungs than we do with ductal, we see more in the ovaries and in the stomach. And it can be really hard because as we know, lobular doesn’t form a mass, and so it can be hard to detect it. That makes it a little bit challenging. And lobular cancers tend to recur later in life. I mean later, like after the initial diagnosis, compared with ductal, which we can see that a little bit earlier. These are all generalizations, and everyone is different.

There is a lot of work being done with lobular breast cancer, which is really incredible. Organizations like the Lobular Breast Cancer Alliance and several others are really focusing on these are different types or different entities and we have to treat them differently.

This is the current treatment landscape, and it’s hard to see. So hopefully I’m going to talk, and you can use these later as a reference. There is an oncologist at Dana-Farber, Dr. Ilana Schlam, who puts these amazing algorithms together. Every time there’s a new drug, she adapts them. This is from December, and I already had to add that box because we just had datopotamab deruxtecan approved just a few weeks ago.

Eleonora Teplinsky, MD [00:05:06]

This walks you through the landscape for hormone receptor-positive, HER2-negative metastatic breast cancer. Understand, these are generalizations, everyone’s going to be a little bit different. But what I’m going to talk about today are antibody-drug conjugates and hormone receptor-positive SERDs, or selective estrogen receptor degraders, and PI3-kinase inhibitors. These are kind of the biggest developments that we’ve seen.

One of the things that Dr. Kaklamani pointed out is that molecular testing of the tumor is critical. This is going to be done at different points depending on the treatment that you are on, depending on if there’s disease progression, but it’s really, really important. And so one of the questions that I urge you to go back to your doctor and say is, Have we molecularly tested my tumor?

That’s going to be different than genetic testing to see if you inherited a germline mutation from mom or from dad like the BRCA mutation that increased your risk of cancer. These are testing the tumor for mutations. And so it’s important to ask that question of has it been done and if not, when should we be doing it, how often should we be doing it.

The PI3K pathway in hormone receptor-positive disease, and Dr. Kaklamani mentioned this, but this is a signaling pathway that is overexpressed or activated in about 35% to 40% of breast cancers. And this can lead to tumor growth, and it can lead to uncontrolled tumor growth. If you do have activation of this pathway, unfortunately it does lead to a little bit of a worse prognosis. But on the flip side, we have drugs now that can target it.

I think you hear this language around this is poor prognostic factor, worse prognosis. And I think it can feel overwhelming and scary and fearful, but understanding that we now have drugs. It’ll be interesting to see how these prognostic factors and what we say about them and the language we use evolves as we develop more medications that can improve outcomes.

Right now in metastatic breast cancer we have three PI3K (kinase) inhibitors that are approved. We have capivasertib, or Truqap. We have inavolisib. I can’t pronounce these, I give up. I don’t even know inavolisib’s brand name. Does anyone know? Genentech? What is it? Itovebi. OK, that’s much easier to say. We go by, we always go by a generic name. And alpelisib.

There are others in development, but these are all approved right now. They all have somewhat of a different efficacy and somewhat of a different side effect profile. So how we pick one versus the other depends on where you are in your lines of therapy and then also side effect profiles.

This is the INAVO120 trial, and this is a new update. This is a study that looked at patients who were currently on endocrine therapy for early-stage breast cancer or who had progressed or developed disease progression or relapse within about 12 months of completion, and patients who had a PI3K mutation.

These were patients that really consider to be high risk, right? If you are on endocrine therapy, you’re on your aromatase inhibitor, and develop metastatic disease, that tells us, hey, this medicine is not doing what it needs to do. Or if you just finished your endocrine therapy and develop metastatic disease, again, it’s not doing what it needed to do.

They looked at these patients who have a PIK3CA mutation, and remember we said about 35% to 40%, these are that high-risk group; they recurred on treatment. They conducted a trial where it was palbociclib, which is the CDK 4/6 inhibitor Ibrance, with fulvestrant, which is a SERD, selective estrogen receptor degrader, and it was either placebo or inavolisib. Inavolisib is a PI3K, or PIK3CA, inhibitor. That’s how they tested it: placebo, Ibrance, fulvestrant or inavolisib, palbo, fulvestrant. This is an oral medication that’s given daily.

The addition of inavolisib improved outcomes. So people did better if they had disease progression, had a PIK3CA mutation, and had just developed metastatic disease after being on endocrine therapy. This became approved very recently, and they had an improvement in the duration of response and an increase in progression-free survival, meaning patients were living longer without their disease progressing.

Eleonora Teplinsky, MD [00:10:12]

You can see some of the side effects here. One of the things that we think about with these PI3K inhibitors is hyperglycemia, or high blood sugar. All of the three that are approved have different rates of hyperglycemia. So depending on which one you’re being offered, you’re going to talk to your doctor about how to best manage the side effects.

And with all of these medications, of course we’re looking at GI toxicity — nausea, vomiting, diarrhea — things like fatigue. For all of these medicines, we’re monitoring your blood work, your liver enzymes. This is just kind of generic for what we’re doing here. Diarrhea is one. These are things that, when you’re talking to your doctor about medication and whatever it is, whether it’s this medicine or another one, it’s really balancing what is the effectiveness of this medicine with the quality of life. How am I going to feel on a day-to-day basis? That’s really, really important.

A key point about this study is that you have to have a PIK3CA mutation. You can do this one of two ways. You can do this as a liquid biopsy, as we talked about in the last session, where you get your blood drawn. These test your blood, matching it against your tumor sample to see if your tumor has this mutation, or they can actually test your biopsy. Some patients may have a recent biopsy that we can test and other times you might not. And so then we would use a blood test.

One of the things that I think is really important to bring up is there was a recent study just published looking at racial disparities in the use of PI3K inhibitors. The big thing here is less Black women are being offered PI3K inhibitors. Less Black women are being offered access and discussion of clinical trials. And one of the reasons that they think this is happening in the PI3K landscape is because of the blood sugar control. We know that Black women may have a higher rate of diabetes, and so people are afraid to even bring up this medication, which is a huge disservice because these medicines work. And so despite having equal numbers of these mutations, Black women were less likely to be offered treatment and less likely to receive that targeted therapy. I think it really is just an important point to highlight that disparities are very, very persistent. I think there’s a whole talk later on disparities in breast cancer treatment. But this study was just published, and I wanted to call attention to it.

Let’s move on to novel endocrine therapies. There’s a lot happening in this space. We have our tamoxifen, we have the aromatase inhibitors, and as we’ve talked about, a lot of resistance can develop. Where most of the research has been so far in terms of what’s approved is on the ESR1 mutation space.

If the tumor, if the cancer develops an ESR1 mutation, what happens is that estrogen receptor just becomes active. It no longer needs estrogen to shut down. It just works and works and works. It doesn’t matter if estrogen’s binding to it, it doesn’t block the receptor.

What we’ve learned is that if there is disease progression, we want to test for that ESR1 mutation. This can be done through the blood in that liquid biopsy, and I’ll talk about elacestrant, which is a drug approved in that space. And what we have is, for patients who develop an ESR1 mutation, are these classes of medications called SERDs, or selective estrogen receptor degraders. What the SERDs do is they degrade the receptor. It breaks down. So it doesn’t really matter if the estrogen’s flowing or not because that drug is going to degrade the receptor.

There are also drugs coming down the pike that are being studied that are called CERANs, complete estrogen receptor antagonist, PROTACs, and several others. They all work by doing something a little bit different to the estrogen receptor. So we’re getting away from blocking estrogen in order to treat the cancer but really focusing on how do we degrade the receptor. Do we block it completely? Do we just degrade it? Do we use these complexes that are going to break it apart? All of the novel therapies are really shifting gears to instead of blocking estrogen but rather doing something to the receptor to kill the cancer.

One of the things that we’re really excited about is: What are the side effect profiles of these medicines? Anyone who’s been on an aromatase inhibitor knows that when you put people into a low-estrogen state, you don’t feel good. We can all agree on that. It’s not just hot flashes and joint pain. In that low-estrogen state, we worry about our heart and our bones and our brains and vaginal dryness and sexual health. So it’ll be really interesting to see whether some of these novel endocrine therapies can overcome some of these side effects because we’re not focusing on the estrogen, we’re focusing on the estrogen receptor. So more work to be done there.

Eleonora Teplinsky, MD [00:15:42]

This picture, it’s kind of small, but what you can see in these three panels is on the left, the orange molecules are estrogen. You see they bind to the estrogen receptor and then all the way in the bottom this cell becomes active. The cancer cells is doing its thing and it’s growing.

In the middle panel is what happens when you have an ESR1 mutation and that receptor is active. It doesn’t respond to the estrogen anymore. Then all the way on the right panel, you see what happens when you give a SERD, a selective estrogen receptor degrader. All of a sudden, that SERD binds to the estrogen receptor and you have decreased activity in the cancer cell, you have decreased growth. That’s where we’re going with these novel therapies.

Fulvestrant, or Faslodex, is a SERD that has been around for a very long time. The challenge with fulvestrant is threefold. One, it’s an intramuscular injection that’s every month, and it’s painful and not really convenient. Number two, it doesn’t really have as great of activity if someone develops disease progression on an aromatase inhibitor. And number three, it overcomes some of the ESR1 mutations but not all of them. There was really a need to say we need something better than fulvestrant. And that’s where these novel SERDs came to be.

We have elacestrant. This is a medicine approved if you have metastatic hormone receptor-positive breast cancer and have developed an ESR1 mutation after treatment with endocrine therapy and a CDK 4/6 inhibitor. This was approved a couple of years ago. It’s a great medicine, it has a lot of effectiveness. This is just one of the SERDs, there’s many more in development, and it will be a great option for our patients with ESR1 mutations.

In terms of side effects, the big thing that we see here, we see some GI side effects, we see nausea, fatigue, vomiting, decreased appetite. We have to monitor cholesterol here. So this is one where the cholesterol can go up. What I like to tell my patients is if we think that elacestrant is going to be an option in the future because we know you have an ESR1 mutation, I have them see a cardiologist as soon as we find that ESR1 mutation to make sure that we’ve got the cholesterol sorted out. Because the last thing that we want is to say I’m going to start this medicine. We get their baseline cholesterol panels and it’s through the roof; now we’re behind. So I like people to think ahead and think about getting this under control so when we need the medicine, you’re optimized. Plus it’s never a bad idea to see a cardiologist anyway. So I think this kind of works out well.

Back at the San Antonio meeting in 2024, we saw results from the EMBER-3 trial. This slide is really more for your reference, but the EMBER-3 trial is looking at a novel SERD called imlunestrant. It’s similar to elacestrant in the sense that it is a next generation oral SERD. This one has brain activity, which is really, really exciting. It also antagonizes the estrogen receptor, so it has a number of different ways that it’s going to work to be active in breast cancer.

They gave this to patients either imlunestrant alone; imlunestrant with Verzenio, or abemaciclib, which is a CDK 4/6 inhibitor; or a standard-of-care endocrine therapy. What they found was that the best combination was imlunestrant with abemaciclib. That was the best one. That worked whether or not you had an ESR1 mutation. So that was really exciting because remember elacestrant, you must have that ESR1 mutation. Imlunestrant alone only worked if you had an ESR1 mutation. But together the imlunestrant and abemaciclib was the best.

When we added abemaciclib, we think about diarrhea. So it’s a balance of the side effects. This regimen is not yet FDA approved, but we are hoping it will be soon and it will be another option for our patients. All of the data here, I’m not going to go into too much detail, but it’s here for you to go back and to look at, especially if this is a drug that gets approved and you’re being offered it, you’ll have these slides here for your reference.

Eleonora Teplinsky, MD [00:20:16]

This press release just came out about a drug called camizestrant. And camizestrant is also an oral SERD. This is a really exciting study because everything I just told you about imlunestrant and elacestrant, this is after disease progression on endocrine therapy. And imlunestrant is not yet FDA approved.

Here what they did was they had patients on an aromatase inhibitor and a CDK 4/6 inhibitor. They monitored them while they were on that treatment for ESR1 mutation. They did blood work every several months to see if they developed an ESR1 mutation. And if they did and they didn’t have imaging progression, they were randomized to receive camizestrant or to continue on their therapy. So it was this early switch concept.

The question of this, and I think this came up in the prior session is: If we do an early switch, are we switching too early or is there actual benefit? Because that’s always the big thing is whenever we switch, what are we trying to achieve. Are we trying to achieve maybe better side effects? Or are we trying to help our patients live longer? And so this was a press release, the data is not out yet. The data should be presented at the ASCO meeting in June. But the press release showed that this early switch approach, so if you have an ESR1 mutation switching to camizestrant was better, and it allowed patients to remain on the CDK 4/6 inhibitor longer without having to switch. So it’s really exciting. We can’t say too much about it yet because this is only a press release from AstraZeneca. We don’t have the full material out yet — I’m sure you can’t share anything with us — but once we see that at ASCO, hopefully this will be something that may potentially be practice changing. We just don’t know yet.

You can see this is all evolving, and where we are today in March is not where we’re going to be in March 2026. I guarantee this talk next year, who’s ever giving it is going to tell you about completely different things because the pace of research is changing that quickly. So we’re waiting for more data here.

Let’s move on to antibody-drug conjugates. Dr. Kaklamani explained this in great detail, but an antibody-drug conjugate really has three parts. It’s got an antibody, it’s got a drug, and they’re joined together by a cleavable linker. The antibody part attacks whatever antibody you’ve designed that drug to attack. Most people have heard of T-DXd, or Enhertu, and that binds to the HER2 antibody. Once it binds, that linker is cleaved, and the drug is injected into the cell.

Some of these ADCs have what’s called a bystander effect. That drug kind of spills out into the neighboring cells, and that’s one of the reasons why T-DXd has been really effective in HER2-low and HER2-ultralow because it has that bystander effect where it gets all the nearby cells around it.

The simplest way that I like to explain this is if you’re ever making donuts — I did this once, it was terrible — and you stuff a jelly donut, the jelly squirts out. That’s the bystander effect. You’ve like literally inserted the jelly and then it goes everywhere. This is why I don’t make donuts ever. The point is that that’s kind of how it works. That’s that bystander effect. It kind of goes and bathes all the nearby cells and that’s why it can be really, really effective in this case.

We have a number of antibody-drug conjugates that are available right now. The big one that we talked about is trastuzumab deruxtecan, or Enhertu. And Enhertu is approved for HER2-positive, HER2-low, and HER2-ultralow. Essentially, if there is even any staining for HER2, even if it’s tiny, tiny, you are a candidate at this point for T-DXd. And there’s been a lot of talk about, we know that even in HER2-zero it may have effectiveness. So there’s been a lot of talk that we may get to a point where if you have metastatic breast cancer, regardless of HER2 status, you’re going to be offered T-DXd. We’re not there yet, but with every approval we see more and more people who are able to get it.

You think about these moments in your career and everyone has an older oncologist that trained me would say, I remember when Herceptin got approved and everyone at ASCO stood up, the standing ovation. When T-DXd was presented at the ASCO meeting a couple years ago for HER2-low, it was a standing ovation because all of a sudden it meant that 50% more patients living with metastatic disease could get T-DXd.

Eleonora Teplinsky, MD [00:25:11]

I remember — so this was in Chicago, presented I think on a Sunday — on Tuesday morning I was back and I called my patient, “We’re ready, let’s go!” And she was the first person to receive it, and we really were running out of options for her. She was able to get T-DXd for almost 18 months, and by then new drugs were approved. Now she’s still, she’s here and she’s living and she’s on more lines of therapy because we were able to get her to a point where there’s new therapy. I think that’s also part of it, that with research, we have more options, and we’re getting more time that we can then offer new medicines.

DESTINY-Breast 04 I believe was presented last year, and this looked at the HER2-ultralow. The big thing with DESTINY-Breast 04 is that to get T-DXd in hormone receptor-positive, you had to have gotten your endocrine therapy, then you had to have chemo, and then you could get T-DXd.

DESTINY-Breast 04 said: Hey, can we give it before chemo? Do we need to get chemo because we’re always trying to delay the onset to chemotherapy. It found that yes, it’s very effective in hormone receptor-positive. You can give it in first line before you need to get to chemo after your endocrine therapy. We’re balancing side effects, but it’s just one more option, one more tool for our patients.

Then we had this DESTINY-Breast 06, that was the T-DXd in ultralow and there’s too many DESTINY trials. I think I may have said the wrong number, but the point is that we have T-DXd in ultralow and also has benefit as well. So any amount of membrane stain you can get this.

Just recently T-DXd was approved for the low or ultralow metastatic breast cancer. This was a recent FDA approval. Super exciting offers us that option for our patients.

One of the things that I do want to get to is interstitial lung disease with T-DXd. This is a big concern, it’s a big side effect, and it happens to about 10% to 12% of patients. Interstitial lung disease or pneumonitis is inflammation of the lungs or fibrosis or scarring of the lungs. And it can present with symptoms such as a cough or shortness of breath or wheezing, it can be kind of vague sometimes. And this is not meant to scare anyone away from using T-DXd because it is a very effective drug. But to say that this is a side effect that people should be aware of.

The company that makes T-DXd has really done an incredible job about educating physicians and healthcare professionals about this side effect. Because one of the things that we want is that if you’re on this medicine and you call in and talk to your nurse and you’re having a cough that we recognize, wait a second, this isn’t just a viral illness, this actually could be a drug toxicity. Let’s stop the drug. Let’s get the imaging. Now it’s not to say that everyone with a cough needs to stop, we don’t panic. But that awareness of the respiratory symptoms is really, really important.

The incidence that I said is about 12%. For the median time to onset, so average time that we see this happening is about 5 1/2 months, but it’s been as early as less than a month and all the way up to about 31 months. It can be very broad in terms of when we can see this. Unfortunately, there have been fatal outcomes reported, but it is very rare.

I don’t say this to scare anyone but to be aware that this is a side effect, and that if we have it, we want to act as early as possible. If we have any suspicion of the symptoms, what we do is we hold T-DXd and we get imaging. If there’s concern we treat with steroids. The majority of cases will resolve on their own, and we’re often able to resume the drug. But just putting that out there as education about the side effects.

Eleonora Teplinsky, MD [00:29:41]

Sacituzumab govitecan, or Trodelvy, is another antibody-drug conjugate that is approved. And this one is approved for hormone receptor-positive and triple-negative. So both of those. This one is not HER2 as the antibody, it’s Trop 2 as the antibody, and it injects topoisomerase inhibitor, which is a metabolite of this drug, SN 38, which is a metabolite of irinotecan.

There have been a number of studies, there’s the ASCENT trial, which looked at sacituzumab govitecan in triple-negative breast cancer. There’s the TROPiCS-02 trial, which looked at hormone receptor-positive breast cancer, and both have been shown to be effective. And sacituzumab govitecan is approved for hormone receptor-positive or triple-negative MBC. And you do not need to have a Trop 2 mutation.

This is one where we are not testing for Trop 2, it doesn’t matter whether it’s present or not, the drug will be effective based on the clinical trials that we have. And sacituzumab is given as an IV, 2 weeks on, 1 week off. So in the third week some of the side effects improve and you can be ready for the next cycle.

These are the study results from ASCENT, and I just want to show you here that this is triple-negative, and they just published the survival data. Overall survival was almost 5 months longer with sacituzumab compared to chemotherapy. Now 5 months is not a lot, I understand that. But 5 months is 5 more months that we didn’t have with the sacituzumab. It allows us then maybe new drugs will get approved, newer therapies and I think we can all agree that 5 months is not a lot. No one is saying that it is. But we’re getting better. There are still huge unmet needs in treating metastatic disease, but we’re moving that needle, even though it’s just a little bit. Every time we move it forward, we’re making some progress. And Trop 2 testing is not required.

In terms of the side effects, we actually don’t really see as much pneumonitis with sacituzumab compared with T-DXd. We can see low blood counts. A lot of patients end up needing a booster shot like Neulasta to try to get them to make sure their blood counts recover. Not for everyone. We see some GI side effects. We’re monitoring all of these.

The big thing we were just talking about earlier with sacituzumab is that you can see fairly significant hair loss. I don’t know if anyone’s been on Trodelvy. Everyone may have had different experiences with hair loss, but for some patients it can be very quick and very rapid. It’s something that we want to prepare patients for. We haven’t seen cold capping work really well with the sacituzumab, but I know a lot of research is still ongoing as to why and can we see improvement there.

TROPiCS-02 was sacituzumab in hormone receptor-positive, HER2-negative, an improvement there. And this was approved about 2 years ago now.

Just recently we had a third ADC join the club, datopotamab deruxtean. This one I know the brand name because it’s easy, it’s Datroway. That’s an easy one to say. This was just approved in hormone receptor-positive, HER2-negative, and this is Trop 2 — just like sacituzumab — and then it’s deruxtecan, which is the drug in T-DXd. So it’s kind of a marriage of both of those Trop 2 to deruxtecan, which we didn’t see.

The question really is where does this fit in. Right now we have three ADCs. A lot of times when we’re deciding between sacituzumab and Enhertu we’re going to pick based on side effects. If someone already has some interstitial lung disease or inflammation in the lungs, maybe Enhertu is not going to be a great choice. We’re balancing based on side effects, based on the profile of the cancer, patient’s wishes and all of that. Where datopotamab fits in is not really quite clear. The other thing is that datopotamab does not have a survival benefit yet based on the data. And so we’re not really sure how we’re going to use this.

There’s a lot of debate about, we know that every time you use an ADC after an ADC, you have a little bit less benefit. So whichever ADC you use first, you kind of get more benefit there, and then it decreases. With the Tropion-Breast 01 trial, which looked at datopotamab, patients didn’t have another, they couldn’t have had an ADC before. So we don’t know what that’s going to look like. And this is where real world data is really important.

When you’re sitting in front of your oncologist and they’re saying to you, I want you to take this medicine. And you ask them, What are the side effects? Especially in these new drugs, we’re just quoting from the clinical trial data. The more patients that we have on it, we can really gather those real world experiences and tell people this is how you do in the real world. Where you’re not monitored every 2 weeks on a clinical trial, where you’ve had all these other medicines that play in, where maybe your blood counts were a little bit not quite there to make you eligible for the trial. As we gather more information, we’ll be able to really share, OK, how does this work drug work in the real world.

Eleonora Teplinsky, MD [00:35:13]

A big thing about datopotamab is ocular toxicity. A lot of the ADCs, especially the ones that we use in gynecologic cancers, also can cause issues with the eyes. You have to be followed. It can be things from blurry vision to significant visual disturbances. So we have to have our patients seen regularly by an eye doctor. This is a part that we have to keep in mind with datopotamab.

Lower incidence of interstitial lung disease, higher incidence of ocular toxicity. So we’ll kind of see how that all plays itself out.

HER2-positive metastatic breast cancer — I want to highlight one study here that was also presented at San Antonio. Before I do that, there’s been a lot of development in HER2 over the last few years, starting with T-DXd and then we have the regimen of Herceptin, tucatinib, and capecitabine, which has a lot of brain activity. If any of you guys have been on this regimen, we saw really tremendous advances, and there’s been a little bit less about HER2 recently. But it doesn’t mean that that research is not being done, it just ebbs and flows.

The PATINA trial was presented at San Antonio and what we know — for today, because this is going to change — if you are newly diagnosed with metastatic HER2-positive breast cancer, you get put on the standard of care is a taxane chemotherapy with Herceptin and Perjeta. After 12 to 18 to 24 weeks depending, we’re able to drop the taxane chemotherapy, if the tumor is behaving and responding or stable, and continue with Herceptin and Perjeta alone. If you were hormone receptor-positive, that’s when we would add the aromatase inhibitor to that.

The PATINA trial looked at should we add a CDK 4/6 inhibitor, because prior to this study there’s been really no significant large trials of CDK 4/6 inhibitors in HER2-positive, but a lot of data suggesting that they would work. This study looked at, so now you’re getting Herceptin, Perjeta, and aromatase inhibitor and a CDK 4/6 inhibitor with palbociclib. This was presented at San Antonio, and it showed improved progression-free survival by over a year, 15 months. Huge!

This is great improvement in overall survival, and palbociclib is one of our three CDK 4/6 inhibitors. I won’t say it’s fallen out of favor, we use it a little bit less these days in hormone receptor positive, but it’s the best tolerated one. So it didn’t add a ton of toxicity when we added it to this triplet regimen. With the palbociclib we do need to monitor blood counts. That’s one of the biggest things. But this really was a significant improvement, and we’re hoping that this is going to be a new standard in HER2-positive, hormone receptor-positive.

In triple-negative. We’ve kind of talked about some of the ADCs, we talked about T-DXd, we talked about sacituzumab, that’s going to be part of that treatment landscape in metastatic breast cancer. One of the things that we do, the first time of a new diagnosis of metastatic TNBC is check for PD-L1 status. If you’re PD-L1 positive, we give chemotherapy with pembrolizumab, which is immunotherapy. Now there’s ongoing trials about what to do with patients that are PD-L1 negative. There’s some data with datopotamab that should be coming out hopefully soon for PD-L1 negative. So we’ll have better options for those patients. But right now it’s chemotherapy in PD-L1 negative and chemotherapy with immunotherapy in PD-L1 positive disease.

Genetic testing is really important because if you have a BRCA mutation you can get a PARP inhibitor. And then we have our antibody-drug conjugates. Lots happening here.

I recognize that this graphic by Dr. Schlam does not look anywhere near as busy as the hormone receptor-positive one, right? They’re a little different. It really highlights how much more work we need to do with triple-negative. But I will tell you that 5 years ago we didn’t have some of the drugs on this page. So we’re making progress.

Eleonora Teplinsky, MD [00:39:54]

Immunotherapy, I’m not going to touch on too much because Dr. Kaklamani explained it very well. But the idea is that we’re telling our immune system to attack the cancer. Typically what happens is, when you get sick and you get a virus, your immune system attacks the virus. When it sees cancer, it kind of has these checkpoints on it that just doesn’t allow the immune system to attack the cancer or to recognize it as foreign. So when we give immune checkpoint inhibitors, it kind of releases the breaks on the immune system and says, hey immune system, go at it. Go attack the cancer. In metastatic triple-negative you need to be PD-L1 positive, but in early-stage triple negative you actually don’t. So those are a little bit of the two differences there.

What can happen is that when you give immunotherapy, and you tell the immune system go attack the cancer, it gets excited and it can attack other organs and that’s what’s called immunotherapy-related adverse events. And it can attack anything, it can attack our thyroid, which is what we commonly see, but really any organ. It can your attack your heart, your brain, your muscles, your lungs, your intestines. People can be fine on therapy and then all of a sudden develop full-blown diarrhea. We scan them and we find colitis or inflammation of the intestines and then we have to give steroids or other immunosuppressive events to kind of tamper down the immune system.

When we first started using immunotherapy, one of the things that they noticed was, they started using it in melanoma, and they gave patients with melanoma these checkpoint inhibitors and they were so excited, and all of a sudden they scanned them and they progressed. It was this kind of like, oh my gosh, is immunotherapy not working? We’ve invested all this research and we’re getting patients who are progressing. So they stopped the medicine. Then they re-scanned them, and they realize, wait a second, actually they’ve now improved. And it developed this concept of called pseudo-progression.

If you’re on immunotherapy, sometimes that first scan things are going to look a little bit worse before they look better. Because the immune system is kind of activating, and it looks swollen and inflamed and can look like someone’s developing disease progression when they’re not. It’s an important concept that we really want to pay attention to.

These are just some of the adverse events that we can see, and you can see essentially any organ is affected. This is one of those things where if you’re on immunotherapy for a long time and you develop a side effect that’s new, bring it to our attention because we do want to do that workup, it could be an adverse event.

I always tell my patients, day to day, most people do really well on immunotherapy. They don’t really have any day-to-day side effects. Things like full-blown diarrhea, nausea, vomiting, you can have a little bit of fatigue, your blood counts can be a little bit low, but it’s not really day-to-day terrible for most people. But if you have an adverse event, it can be really be full blown and we want to evaluate that very quickly.

There’s many trials that are ongoing for metastatic, but I wanted to highlight some of the TNBC ones especially since it is TNBC month. And you see the landscape not look as big. But I want to share some of the really exciting studies that are ongoing.

There is Tropion-Breast 02. This is datopotamab, that new ADC that was just approved, in first-line triple-negative breast cancer in patients who are not eligible for immunotherapy, which I think is going to be really, really important. We feel like we don’t have a lot to offer those patients and we’re putting them on chemo. And we know that even if the chemo works, in 12 weeks they’re going to be beat up from that chemo and it’s going to be hard to keep going. So really excited to see what this study shows us.

There’s Tropion-Breast 05, which is datopotamab deruxtean plus or minus durvalumab, which is an immunotherapy for patients that are PD-L1 positive metastatic TNBC. And then we have the Saci-IO study, which is PD-L1 negative, and then sacituzumab with immunotherapy to see if we can overcome that PD-L1 negativity by adding sacituzumab and many more. There’s a lot ongoing, and we’re hoping some of these will report out soon and will offer more options so that when we’re here in a year, that landscape’s going to be bigger, that we’re going to have more drugs to add to that space.

A lot of questions recently about vaccine trials in breast cancer. There is a lot ongoing. Right now there is no vaccine that has been approved to treat breast cancer. But there are a lot of studies, there’s studies in HER2, there’s studies in triple-negative. There’s studies about can we give vaccines to prevent, can we give them to treat. So a lot happening right now, but nothing that is approved yet.

I will say that there’ve been a lot of, there’s been a lot floating around the internet these days about potential impact on the trials, some of these vaccine trials, and budget cuts. I think we just don’t know much yet. A lot circulating and creating, of course, fear and nervousness and anxiety. But we don’t know what’s happening quite yet there.

Eleonora Teplinsky, MD [00:45:02]

I just wanted to take a minute to talk about updates in brain metastases because this is a question that always comes up. You can see there’s different algorithms here about what to do. But in someone who has newly diagnosed brain metastases, essentially what we want to figure out is, Is this something that can be resectable? Should it be resected? Can we give radiation?

We try to give really focused radiation or stereotactic radiosurgery so we don’t have to radiate the whole brain, which can create more cognitive impact. We figure out can we give SBRT or stereotactic radiosurgery versus whole brain radiation therapy. And I will say the radiation oncologists have come a really long way in trying to give medicines and do whole brain radiation that’s hippocampal sparing and that protects some of that cognitive decline that we used to see with whole brain radiation. So it’s certainly a lot better than it has been in the past.

Then the other part that we have to figure out is, What do we do with our systemic therapy? In some cases now if we have good therapy that’s going to cross the blood-brain barrier, sometimes we’re able to think about do we do that and postpone the radiation. So a lot is happening in terms of how we approach the disease, but we’re thinking about is there also disease progression in the body. What treatment was someone on? Were they on treatment that penetrated the blood-brain barrier? Can we switch them to a blood-brain barrier penetrant treatment? So a lot’s happening in this space as well.

I just wanted to show you here that, I tried to find a list of trials that are ongoing, and this was, I think there were three pages. I only put one page of the trials in brain metastases, but just to show you how much work is ongoing right now. I think everyone recognizes that brain metastases are an unmet need, in treating them, preventing them, screening for them, both in patients with early-stage breast cancer and metastatic.

There’s been a lot of discussion about, as we get better with our systemic therapies, we know a lot of them don’t penetrate into the brain. So the brain almost becomes what’s called a sanctuary site where the cancer cells can go because there’s no treatment penetrating up there. So should we be screening for brain metastases? How often? The standard has always been we don’t do it in the absence of symptoms. And that paradigm is changing. A lot of people are starting to have this discussion and conversation about what to do. I will say that I usually have that conversation with my patients about should we be screening for brain metastases. Especially in patients who have really well controlled disease in the body, we’ll periodically think about doing brain MRIs. And that’s an ongoing discussion.

In conclusion, metastatic breast cancer continues to evolve. These are just some of the updates. But as we see new drug approvals, we see research evolve. It’s really exciting to see this progress. None of these drugs were around a few years ago, and I think a lot of you have seen and been on some of them.

As we do that, I think the most important thing that we do, two things. One, we have to diversify clinical trials. We have to study the patients that represent the face of metastatic breast cancer because we can’t sit in front of a patient and say, I don’t really know how you’re going to respond because maybe this was an 80%, 95% Caucasian trial. And so we have to improve diversity in clinical trials. That’s a huge priority of a number of organizations.

But I think no matter what we do, the patient has to be at the center of it. I feel very encouraged. To be here and speaking, you guys are all such amazing advocates, and whether you advocate for yourself, for your community, on a national level, it’s so important. And I have been so encouraged to see organizations and pharmaceutical companies and governmental agencies that are putting patients on the steering committee for trials, that are listening to patients. Because when we as oncologists or researchers stand up and say, “Well, the safety was tolerable.” What does that mean? We all know that even one episode of diarrhea a day is not really tolerable. I think as we move forward, we really have to think about quality of life and how to really help people thrive with metastatic disease. Thank you so much.

Jean Sachs, MSS, MLSP [00:49:38]

Thank you so much, Dr. Teplinsky. I’m sure you’re all confused, right? This is a lot of information, and you’re right in saying so much is changing so quickly. So much has changed in the last even 5 years.

Caroline and Holly are going to help me do this, but I’ll just start with, there’s a bunch of questions about can you go back to some of these treatments. So one specific one is: If you were on a CDK 4/6 and also fulvestrant and both failed and then you’re moving to an ADC, can you move back and try one of these new SERDs?

Eleonora Teplinsky, MD [00:50:22]

Absolutely. I think that the challenge with any clinical trials, and you can ask this question for really any medicine, as new things get approved.

The challenge with trials is that it takes a decade plus to bring a drug to market, so what happens is when the trials are enrolling patients. We saw this in the datopotamab study, it didn’t allow prior antibody-drug conjugates. So now we don’t really have data to say what’s the effectiveness going to be if we give you datopotamab if you’ve already had sacituzumab. And the same thing with the novel ADCs. Can we go back?

In general, yes. I think that this is where having those conversations with your oncologist about what do we know, what do we not know, and thinking about safety. Because we’re not going to know everything. The research is not going to keep up as quickly as what we need on a day-to-day basis in the clinic. So the answer is always, let’s talk about it.

A lot of times, too, you see at the meetings, the big thing that’s splashed around, that’s on the media headlines is the phase III trials that have hundreds of patients. But there are researchers that are looking at these small subsets of can you go back, and that doesn’t always make the podium. But there always is some data. There’s always maybe a study of 30 patients, and let’s see what happened. So I think talking to your oncologist and asking are there smaller trials that may support this is important.

I think this is where having that relationship with your oncologist is important. And get a second opinion, get a third opinion, get a fourth opinion. Because no one is going to care as much about your disease as you will. And so the more people you can talk to, the better it’s going to be.

Caroline Koffke, RN, BSN, OCN [00:52:20]

We have lots of questions about treating the disease based on location. Do you treat patients with different drugs depending on the location of the metastases?

Eleonora Teplinsky, MD [00:52:32]

Yes and no.

I think it’s more about toxicity here. So I’ll give the example of lung disease. Let’s say someone has a lot of disease in the lungs, and they’re already very symptomatic from a lung cancer standpoint. As we think about ADCs, maybe we would pick one that doesn’t have that lung toxicity just because it can be hard to tease out and evaluate. But there isn’t, at this point, large, robust data that says, based on this site of metastases, we should treat with this.

With that said, if you do have brain metastases, some regimens are going to be more brain penetrant than others. So in those cases, absolutely we want to think about, medicines that are going to penetrate into the brain. If you do have bone metastases, we definitely want to make sure we’re thinking about bone modifying agents like denosumab or zoledronic acid. But generally we’re kind of thinking about the disease as a whole. And balancing side effects, and looking at every single person as an individual.

Holly Hernandez [00:53:40]

When you consider antibody-drug conjugates and a patient goes no evidence of active disease on that, what is the protocol to continue on that drug? Are you lowering the dose? Are you putting more time between? Or are they staying on the same protocol?

Eleonora Teplinsky, MD [00:54:00]

I had this conversation yesterday, actually. I have a woman, she’s triple-negative and she’s been on T-DXd for I would say about almost a year and a half. We’ve lowered the dose to the lowest dose and she still has some side effects and she’s struggling. So we had this conversation about what do we do. And there’s really not a lot of data to tell us what we should do in these situations.

I will say I’ve had some patients where I’ve done a little treatment holiday, We’ll take one or two sessions off, and come back. Sometimes we’ll do this around holidays or vacations with the understanding that we don’t have robust data to point us in one way or another, but we’re balancing quality of life.

Some patients are nervous, and she’s really nervous to stop. She said maybe we’ll skip one, and I’m going to see how I feel. But if we are taking a break, I do tend to kind of bump up the imaging, and do it a little bit more often. In some patients with metastatic disease, I’m using circulating tumor DNA testing. I find that that can be in some people more reliable than tumor markers, again individualized. And so maybe in those patients, if we’re taking a break or stopping, we’ll bump up our cadence of that monitoring. But really thinking about it on a case-by-case basis.

Jean Sachs, MSS, MLSP [00:55:27]

Great. Someone’s asking a question. What about proton therapy on MBC, especially people with brain mets?

Eleonora Teplinsky, MD [00:55:37]

It’s a great, great question. Proton therapy tends to be a little bit more side effect-sparing. So in patients with leptomeningeal disease, which is disease that’s involving the brain and the spinal cord, we do like to think about proton therapy in those cases because it can improve toxicity.

The challenge is that very few places offer it. It’s very expensive. In the New York, New Jersey area, there’s a place in Somerset, not far from here, that is really one of the only centers that does it, and it’s thousands of dollars if your insurance doesn’t cover it out of pocket. So it’s really a balance, but it is something that we do use and think about for leptomeningeal disease.

Jean Sachs, MSS, MLSP [00:56:20]

I’m going to also ask, so a couple people have said, If they’re doing well on their current treatment, should they stay on their treatment or should they be looking for a trial? And is it important? Like at what point does it make sense to switch?

Eleonora Teplinsky, MD [00:56:38]

It’s a great question. Now, typically, unless we have a trial like SERENA-6 where they’re looking for those emergence of mutations and switching, most clinical trials you would switch upon disease progression. But here’s the thing: We do think it’s important to think ahead.

Now, if you’re a disease has been stable for several years, that’s very different than cancer that’s kind of growing a little bit more quickly. But let’s say you get a PET scan or a CAT scan and it shows disease progression, and then we start thinking about a clinical trial that’s at a different institution, so to speak. Then you have to establish care with that institution. They have to get your records, they have to get you an appointment, and now time is ticking.

I think that if you were thinking about a clinical trial somewhere else, I think it’s good to meet that team early on or when your disease is stable so that you’re already established, they’ve gotten your records, you’ve gotten necessary testing, and you have a plan. I like to think ahead, I hate surprises. And so I like to know, if this progresses, what are we thinking about next. If your institution has a trial, then we obviously typically would wait until that disease progression. But if you’re thinking about going elsewhere, it’s an important thing.

I think it’s a great question to ask your oncologist and say, “I know that my disease is stable right now. What do you think we would do next if there’s disease progression?” And there may not be a clear answer because it may depend on, When are we talking about progression? Is something new coming? But at least you can get an idea, and you can follow that with, would it be beneficial for me to seek out potential clinical trials knowing that I would kind of save them for the time of progression. Because then you’re just preparing. You’re not saying that’s it, my disease is progressing, but you have a plan. And I think having a plan relieves a lot of the fears that many people have.

Holly Hernandez [00:58:41]

There are people asking, can we add different targets based on the antibody-drug conjugate idea like CDK 4/6 inhibitors?

Eleonora Teplinsky, MD [00:58:56]

I think the challenge is we have to be a little bit careful about adding a lot of things together because we also want to balance side effects and safety. We have to know will there be any new safety signals. Sometimes this drug can do this, and this drug can do that. Then you combine them together, and it can be really, really toxic. So I think we have to be careful.

And I think that it’s really still important to follow the data. Now understanding that we might not always have it, but thinking about is it safe. If we really don’t have any signal of safety, we really have to be very careful with that because we just sometimes don’t know how two drugs are going to interact. So we do want to share what’s been done.

There might be a small study that’s been done, or sometimes we’ll do things that are being studied in clinical trials in unique situations if someone can’t get on a trial. But at least we know it’s being studied on that trial. And these are very unique situations that really require a lot discussion.

Caroline Koffke, RN, BSN, OCN [00:59:58]

Have you seen SERDs being used in the triple-positive community?

Eleonora Teplinsky, MD [01:00:06]

Not yet. I’m sure there are ongoing trials, but nothing that is used in clinical practice at this time.

Jean Sachs, MSS, MLSP [01:00:16]

Given the side effects for those with the PIK3CA mutation, how is that treated?

Eleonora Teplinsky, MD [01:00:24]

For anything, as we think about how we treat them, it’s based on the side effects and understanding that side effects are going to manifest differently in each person.

The big thing with hyperglycemia for the PI3K inhibitors is each of the drugs, has a different degree of hyperglycemia. So that’s really important. We should be monitoring fasting blood sugars and hemoglobin A1C levels. We want to have those in advance. And if you have someone with diabetes, this is where we want to optimize in advance if we think we’re going to use those.

For example, I told you about molecular testing and looking for that PIK3CA mutation. If we’re not using it in first line but we know that someone has a PIK3CA mutation and it’s going to come up in the future, they should see an endocrinologist if they have poorly controlled diabetes so that, that can be controlled in advance.

Then once you start on the medication, each of the drugs has very specific labels about how often to check the blood sugars, what to do if they get above a certain point, what to start. And I love to work with our endocrinologists, our ophthalmologist, our cardiologist, everyone that can help us manage those side effects. That’s really important.

What you can do is ask your oncologist, If my blood sugar goes up, what’s the plan? Should I see an endocrinologist? Do you have someone that you work with? Because we all know these appointments can be hard to get. And what we’ll do is we’ll start the medicine for someone if they need it, and then we’re helping them get an appointment. If you’re treated in community centers — I’m kind of in a hybrid — but that’s not always possible. So I think being your own advocate in important. I would love to tell you that in every place, everyone is being offered these things and has easy access to all these specialists, and we know that’s not true. But by being here and knowing this information, you can advocate for yourself to make sure you have all of these specialists lined up to help you.

Caroline Koffke, RN, BSN, OCN [01:02:28]

Building off of that, we know that there are a number of side effects, some of which we know, some of which may come to light as you said, in practice, as more people receive these medications. What are your strategies for conveying dose changes? Explaining your symptoms to your doctor? And presenting that to your doctor so that you can get the support that you need and potentially reduce doses or change cadence.

Eleonora Teplinsky, MD [01:02:59]

I think the best advice that I can give is be really straightforward about what you are asking. And I say this in this way, that if you were thinking about a dose change, tell me. Come into your meeting or send me a message the day before and say, “I know we have an appointment, I’d like to talk about a dose change.” Because sometimes people are thinking it, but they don’t say it.

Fatigue means different things to different people. Nausea means different things to different people. And when we think about when we grade it right, a lot of the side effects have to do with how does it impact your “activities of daily living” or your quality of life. It’s going to be different for different people. So it’s really important to be very honest. I think what happens is sometimes people are nervous, or there’s not enough time or the doctor didn’t bring it up. I think just be really honest about what you are hoping to get.

Two other things with that. If you don’t have enough time in that visit, make a special appointment, it could be telehealth, to say, “I’d really like to talk about this concern that I’m having.” And bring someone with you. Bring someone with you to the appointment that is going to advocate for you and that’s going to speak up, even if you feel uncomfortable, and say, “I’d like to talk about a dose reduction or a change.” And understand that all of the drugs have dose reductions built in that are safe and that are effective. Each drug in their package labeling will say, you can go down to this, you can go down to this. And then after that you can’t go down anymore. They won’t allow doses that have not been proven to be effective. And I can’t tell you, and we see this so much with the CDK 4/6 inhibitors, that people are struggling on the highest dose, and there have been so many studies that have said dose reductions do not compromise efficacy. Lends the question of, well why are we not starting at the middle dose then. Right. Well for some people, a lot of that is dose dependent for each individual.

Know that there are safe ways to dose reduce, but bring it up. Don’t be afraid of that conversation.

Jean Sachs, MSS, MLSP [01:05:05]

That was going to be my follow-up question. Do you always start your patients at the maximum tolerated dose?

Eleonora Teplinsky, MD [01:05:13]

No. It depends on what other side effects they’re coming in with. If they’re already dealing with intense fatigue and this drug is known to cause fatigue, I won’t. We’ll start at the middle dose. Depends on age, other medical factors, what their day-to-day life looks like. And we can always tweak it. If I do start at the highest dose, I’m very clear that we can dose reduce. Sometimes we’ll start at the middle dose and, if they do well with that first or second time, we can go up. So it’s really individualized.

Holly Hernandez [01:05:51]

If a CDK and fulvestrant have failed and you move on to an antibody-drug conjugate, can you go back and try one of these new SERDs or is it not likely to work?

Eleonora Teplinsky, MD [01:06:03]

I think we maybe covered that question, but yes you can individualize and we can think about that.

Jean Sachs, MSS, MLSP [01:06:09]

I love this next question, and I have a story, it’ll be quick. The question is, What about the rate of infusion? This person’s on Enhertu at 90 minutes, but they started at 30 minutes.

I did recently talk to a man whose wife was on Perjeta and Herceptin but was having an allergic reaction. So he actually learned how to use the chemotherapy infusion, and he sat with her for every therapy and slowed down the dose so she could tolerate it. It was kind of amazing.

But what about that? Because I think that’s something people don’t always know to ask about.

Eleonora Teplinsky, MD [01:06:46]

I think this is a great, great topic. And we actually learned about this from patients and from patient support groups.

People were coming in and they’re saying, “I saw in my support group.” I forget which drug, but they saw in their support group that a longer infusion, people were doing better with that. That’s that real world experience that we learn from. And that’s why these communities are so important.

I think, absolutely, we don’t have — again, it depends on each drug — a ton of large clinical trial data that says you can slow it down, but we know anecdotally that it really helps some people with side effects. So that is something that we can employ. Absolutely.

I think that this is something that if you see it in your support group, bring it up. I can imagine that some people are met with “That doesn’t work,” “That’s just one person’s experience.” But really push. And I think asking the question of is it harmful to slow it down, we know that it’s not. So can we try it and can I see how I feel. It gets a little tricky in terms of support because it increases the time in the chair, in the infusion center. And for a lot of infusion centers that are limited on space, that can be a problem. But I really would try to push and say, “Let me try it, and if I feel better ...”

The data on this is anecdotal and it depends on drugs. So it’s not like everyone needs a longer infusion time, but if you’re having side effects, and in some drugs that may be something we can consider.

Holly Hernandez [01:08:22]

Do you see any benefit to adding tumor testing in the early-stage setting versus waiting until the metastatic setting? Adding additional testing?

Eleonora Teplinsky, MD [01:08:32]

I think it depends on what that additional testing is. We know that there can be discordance between early-stage and metastatic mutations and molecular changes.

Let’s say we test your original tumor and find out you have a PIK3CA mutation, we don’t know what to do with that information. As we think about testing it’s, Is it actionable? Can we do something with it? Is it going to help you live longer or with better quality of life? Right now we’re not routinely doing molecular testing on early-stage cancer unless we are acting about it for a clinical trial. But that may change in the future as things develop and new targets evolve.

Jean Sachs, MSS, MLSP [01:09:24]

And then there’s a question, is there any significance to the androgen receptor in breast cancer?

Eleonora Teplinsky, MD [01:09:31]

The androgen receptor is one that we see more expressed in triple-negative breast cancer. There have been a number of trials really trying to think about targeting the androgen receptor, and still some that are ongoing. There’s some data maybe, but nothing that’s really robust or meaningful in terms of significantly improved outcomes. But more work is being done. It’s not something that we routinely do and think about at this point, but it will evolve.

There’s a lot of work going into subtyping, especially triple-negative breast cancers. The idea that not all breast cancers are the same, and we kind of treat all TNBC cancer similarly right now. We test for PD-L1 but we’re not looking at basal-like, luminal-like, different subtypes, immuno modulatory subtypes. As that research evolves, I think we’ll get more data into how to really think about each case in an even more personalized way.

Caroline Koffke, RN, BSN, OCN [01:10:27]

I asked a similar question to Dr. Kaklamani but would love your opinion as well. Obviously there’s lots of trials ongoing, lots of new information coming at this community, which is amazing and exciting. But what are some of the resources that you give your patients to help navigate the influx of information and finding trials or things that might be right for them?

Eleonora Teplinsky, MD [01:10:50]

I think that there is a lot of information, and I think here is where some of the things you see on social media are great and some are not. Because what happens is some of the studies, whether they’re preclinical or not, sometimes get picked up by the media, and the media runs with it. And the media loves splashy headlines that are often sensationalized and are not accurate. So it can be really hard. It’s hard for me to parse it out half of the time too, because they want to sell their story. They want you to stay on their page and read it, and it can be really hard to tease out if this study, People Magazine just ran something, the headline was so wrong.

I think it’s really important to go to patient groups like Living Beyond Breast Cancer, the American Cancer Society, ASCO, cancer.gov, there’s all of these really great resources that you can go to that are trustworthy, that are vetted by medical advisors, that are people that are knowledgeable and in the field saying, yes, this is promising. Or wait a second, let’s slow down and hold on a second.

I think that it’s really important to use those groups. Here’s where trusting your medical team is so important, because you want to have a place where you can go and say, “I saw this online. I saw this on my support group. Can we talk about it?” It’s a big difference to separate individual stories from what we know in terms of large data, and everyone’s story different, everyone’s experience is different.

I get it. I mean if you are being offered a drug and then you hear about several women who’ve had a really hard experience with that drug, it can be really hard to mentally prepare yourself to go on these side effects. But it’s really important to understand too that there are people with each drug that are doing well. So having all of those resources and communities is important. I think for clinical trials, clinicaltrials.gov is a great place. It’s hard to navigate, and sometimes things aren’t updated as quickly as we’d like them to. So it can be hard to see is this trial accruing or not. But on clinicaltrials.gov, all of the trials have a contact number that goes to a human at that site. It usually goes to someone in the research office, and they can talk to you. They can screen you over the phone, and they can give you that information.

A number of the advocacy groups are really starting to get involved in helping connect people with trials.

Lastly, a lot of the companies that do molecular testing, if there is a trial in your area, they actually, if you have a mutation, they actually will in the report will give you that information like you may qualify for this trial. So that’s yet another way to get that information. And that can be really helpful if you are at a community place or somewhere that maybe your oncologist wasn’t aware of the trials. Those molecular testing companies are really providing us with a great resource.

Jean Sachs, MSS, MLSP [01:13:57]

How many people in the room are on a clinical trial? And if you’re watching by livestream, if you could put it in the chat just to get a sense. OK, so some. Not a ton. Not everybody.

Eleonora Teplinsky, MD [01:14:09]

But or how many have been on a clinical trial in the past.

Jean Sachs, MSS, MLSP [01:14:11]

Right. Better question. OK, great. So obviously talking and learning from each other is a great way to do it.

Eleonora Teplinsky, MD [01:14:19]

I’ll just add one thing is that if your oncologist hasn’t brought up clinical trials, it may be because there aren’t any right now. And I think it’s an important question to say is, Are there any clinical trials? Or am I a candidate for a clinical trial in the future? Just so you start planting and having that conversation.

Caroline Koffke, RN, BSN, OCN [01:14:39]

We talked briefly earlier, and you’ve mentioned it briefly today, about federal funding and just being concerned about the future of clinical trials. Obviously we’ve seen incredible progress from them. Have you noticed any changes in your own momentum or your own clinical trials with changes in the administration?

Eleonora Teplinsky, MD [01:14:57]

Nothing yet, which is great for today. We don’t know how this is going to evolve. A lot of the funding cuts right now are proposed. As of Thursday or Friday, I think the federal judge blocked some of them from going into effect. But we don’t know what’s going to happen. I think this is really an evolving field, and what we all can do because there’s a lot we can’t do.

But what we all can do is contact our elected officials, our lawmakers, and share your story. ASCO has their advocacy ACT network, and on their ACT networks website, they’ve drafted letters for you. Put in your zip code and they will draft letters to all your elected officials. And you can change those letters to share your story. I think the more we do that and the collective voice I think is really important.

It’s an evolving field, and we will see what happens. I don’t know, and I think this is where, as Dr. Kaklamani said, there’s going to be a lot of people, about, I think it’s like 10%, don’t quote me on this number, of trials that are federally funded. The majority are not. And the federally funded trials are so important, but we have to lean on all of our other partners that we work with for the trials, if there are cuts, to hopefully make up some of that difference.

Jean Sachs, MSS, MLSP [01:16:15]

Thank you. Someone’s asking a question. What are medical oncologists, what kind of continuing education is required? Because we know that not all oncologists are like you reading all the studies and going to all the meetings.

Eleonora Teplinsky, MD [01:16:30]

It’s a great question. To maintain board certification you have to do continuing medical education. However, it’s not really specified what that continuing medical education is. You could do survivorship education, you could do new drugs.

Most oncologists get that by going to conferences like ASCO, where you can get CME, but it’s not really regulated into like what kind of CME you have. A lot of accredited breast centers require that their doctors do breast-specific continuing medical education. For example, if you’re at a place where you treat multiple cancers, you could get your CME for lung cancer for example. But if you are at an accredited breast center and you practice breast oncology, you have to have breast-specific CME. But even that can vary. It’s not as prescriptive as it could be.

Caroline Koffke, RN, BSN, OCN [01:17:33]

You mentioned ctDNA tests earlier, and I know we’ve talked a lot about biomarker tests. Can you just briefly explain the difference between those two tests and how you use them?

Eleonora Teplinsky, MD [01:17:42]

Absolutely. There’s a little bit of overlap, but the idea is that circulating tumor DNA, so all of our cells shed DNA into the bloodstream including tumor cells. The idea with the circulating tumor DNA is that as the cells die, they shed DNA and you can pick that up. And those are tumor informed assays. They actually took a sample of your tumor and they created kind of an assay or a blood profile from it that they can then measure in the blood. And the ctDNA testing can quantify it. So if you’re monitoring every so often, every few weeks, and you see the ctDNA going up, it can be a guide. OK, maybe we should do our scans earlier.

Just like with tumor markers, we have situations where the ctDNA is climbing, and the scans look the same. And we don’t know what to do in that case because switching early that begs the question of are we just going to change therapies and maybe wouldn’t have made a difference. So we need more data in that space.

When we think about biomarker testing, we’re not looking, we’re specifically looking for particular mutations. So we’re looking for ESR1, we’re looking for PIK3CA. So there’s some same idea in that liquid biopsy, but a little different in terms of what we’re looking for.