Medical advances in the treatment of metastatic breast cancer

Transcript

Maryam Lustberg, MD, MPH [00:00]

I know it’s a lot of information that we’ll be covering. I had the chance to hear Dr. [Debu] Tripathy’s presentation. We’ll be touching on a lot of the themes that he introduced as well. I want to assure you that your questions will not be unanswered. So anything that we can’t get to on the panel, I’ll be here after the session formally ends. I’m happy to speak to you one-on-one, and my email will be at the last slide, and I’m happy to get questions.

I also wanted to take a moment to acknowledge a tremendous loss that the metastatic breast cancer community has experienced since yesterday, which is the loss of Sheila Johnson, who was an incredible patient advocate and leader who lived with metastatic breast cancer for 15 years and was a trusted colleague who I had the fortune of working with on multiple grants and papers, and just a wonderful human being.

So we’ll be delving into all the different subtypes of breast cancer, which is of course very, very important. But I thought to, initially, while we’re all together, I thought it was also important to talk a little bit broadly about what I call the clouds and the fog that surrounds cancer biology and cancer subtypes. And my hope is that, as we have this conversation today, there will be a little bit more clarity as we go forward.

In the year 2000, so almost 24 years ago, there was a publication that was called “The Hallmarks of Cancer,” where several key pathways were identified, which helped us understand kind of what was actually driving tumor cells to grow.

Well, since then, 24 years later, this “Hallmarks of Cancer” has been updated to include multiple additional factors. And some of these were referred to by Dr. Tripathy and that includes the genetic landscape of the tumor, what’s driving the tumor. But just like we function as a community—that we’re all together and we’re tied and there are multiple connections that we all have—these tumor cells also don’t exist in a vacuum. And the environment that surrounds them, there are multiple factors that feed into this. And this updated “Hallmarks of Cancer” really, acknowledges that.

The tissue environment, the other factors that can influence tumor growth, again, stressing the complexity. And I’m not making excuses why we’re not making progress fast enough. We are making progress. It absolutely needs to be quicker. But all these clouds, all these factors are what influences tumor biology and can make that task a lot more challenging. A big headline in the last year or two and even beyond, and it made additional headlines this week, was that we really want to… you know, we talk about breast cancer, lung cancer, brain tumors, but we also talk about targeted therapies. And there’s been a really unified effort to think about a tumor agnostic way.

I was hearing conversations in the background during the break and people were like, “People are talking about tumor agnostic way.” So this is a truly sophisticated audience. But the idea is if we have a protein target on the tumor, does it really matter where the tumor actually originated. There’s been a lot of exciting efforts that have been led by scientists and advocates that have really emphasized this point, and it has led to the approval of what we call tissue-agnostic FDA approval of certain drugs. This only opens additional therapies for patients with breast cancer.

So the idea is if there’s a high mutational burden, that opens the door for any patient with breast cancer to have access to, for example, immunotherapy. So there’s going to be additions.

Lots of this space is going to be expanding in the next decade. I’m very hopeful that this will allow me to look at that tumor tissue biopsy that Dr. Tripathy was talking about, and if I see a target, it doesn’t matter if the original studies were not done in breast cancer, I would be able to—one day be able to—give you these drugs.

Lots of exciting news in a lot of the pathways that he referred to, including the PI3K pathway, lots of work on genetic pathways such as BRCA, and just this past this month we had the FDA approval of Enhertu for all solid tumors that are HER2-expressing.

Now, you might say, as a patient with metastatic breast cancer, “Well, this doesn’t really help me, we already had that approval in breast cancer.” The reason I’m choosing to highlight this is that this is going to be a major advance for other indications. This is setting the precedence that we can use tumor agnostic ways to bring more drugs to you more quickly.

Maryam Lustberg, MD, MPH [05:23]

I think one of the themes of this meeting is going to be drugs and drugs and drugs and innovative mechanisms. So I thought it would be nice to just look at a cartoon, because sometimes when we talk about these fancy drugs, it can be hard to conceptualize what’s happening.

T-DXd also known as Enhertu is an antibody-drug conjugate. I will be speaking about multiple antibody-drug conjugates during the meeting, and the principles of this mechanism that you see here are going to apply to all of them in essence.

The idea is there’s a target on the tumor cell and there’s a binding to that target through that antibody, and then it internalizes into the tumor cell. And due to immense advances in technology, that antibody, which is linked to a chemo drug, gets to release the drug. And the chemo gets actually released exactly where the tumor is expressing the target. It’s a very elegant way of delivering chemotherapy. Very different from our traditional chemotherapy.

Chemotherapy has a role, and this—in essence—is releasing chemotherapy, but it is a distinct mechanism of a more targeted approach. And then some of the chemo actually diffuses out to other adjoining cells that may have not either picked up the drug for whatever reason or they didn’t have the target. And this is called the bystander effect. So it further synergizes the antitumor efficacy. Now, it may lead to additional toxicity as well, so I’m not meaning to minimize that in any way, but really this is a powerful foundation for drug development that is going to rock our world.

In reviewing the most recent AACR [American Association for Cancer Research] meeting that just took place, multiple companies are focusing on how to improve this mechanism. How can we improve the antibody? How can we improve that linker technology? How can we add more innovative chemo agents so that we have more opportunities in sequencing?

So this is indeed an important advance that we’re going to continue to build on. But let’s delve more into breast cancer; that’s what we’re here to learn about.

In terms of the subtypes of breast cancer, you have—and Dr. Tripathy did a really nice job focusing on—the hormone receptor-positive pathway, the HER2-positive overexpressing tumors and also those that we call triple negative, where we are not seeing expression of ER, PR or HER2. So this is a little bit of a review for this really sophisticated audience, but I really wanted to acknowledge that these are the subtypes that I’ll be covering in more detail.

And I do not want to forget about HER2-low because again, from us focusing on these very distinct subtypes, the recognition that maybe things are not either/or. It’s not whether you’re HER2-positive or HER2-negative, that even a little bit of HER2 expression can give us a powerful way to target that tumor because our drugs are better.

It’s not that we always knew there was a little bit of HER2 expression. As you can see in this figure, 62 percent of the hormone receptor-positive breast cancers have low levels of HER2 and a third of triple-negative breast cancers have HER2-low as well. We knew this, this is not new information. So we just kind of knew this and we were going around decade after decade really not knowing what to do with it. But because we have new drugs now that can target and go after this HER2 signal, this has really defined this as an opportunity for us to treat.

Before I delve into the different subtypes, I just wanted to again, acknowledge the collective community that we have been. I have had the fortune of really learning from a diverse group of patient advocates over the last 20 years that I have been a medical oncologist. And really the messages have been heard and I think that the oncology community is listening. The idea that we need precision medicine, personalized medicine. It’s not about giving you too much drug or too little drug. I want to give you the right amount of drug. And I’ve learned from fellow advocates to not call things de-escalation or escalation, but really what we’re talking about is right-sizing our therapies. So that’s what we’ll be talking about.

Maryam Lustberg, MD, MPH [10:16]

So the next few chapters will be focusing on the different subtypes of breast cancer. If you don’t have hormone receptor-positive breast cancer, you can stretch and relax. But there will be some points of connection that I will highlight.

Anybody know what this might be? It’s a crystal picture of something. It’s a crystal picture of the estrogen receptor, and it really highlights the complexity of this one target that has completely revolutionized how we treat breast cancer. Before precision medicine was the vogue term, when we were treating breast cancer with estrogen deprivation therapy we were practicing precision medicine because we were going after this target.

That red bubble and blue is where the estrogen is actually binding in this very complex structure, and when the binding happens, it localizes into the nucleus, the center of the cell, and starts this cascade of cellular perforation and activation. Dr. Tripathy covered this a little bit, so I’m not going to spend too much time on this, but what we’re talking about is estrogen binds to the receptor. This is a simplified cartoon, but I think it serves the principle. Essentially it’s a lock-and-key model. Estrogen binds to the receptor, it starts a whole cascade of activation. Then tamoxifen—which it’s been said that tamoxifen has saved more lives than any other cancer drug in history due to the commonness of breast cancer and because it is such an effective drug—essentially competing with estrogen for that lock and key. So if you have tamoxifen binding to the receptor, then the estrogen cannot further activate things.

You heard a little bit about the aromatase inhibitors, which is another class of drugs. The names that you will recognize are things like Femara [letrozole], Aromasin [exemestane] and Arimidex [anastrozole].

Essentially what these drugs do is they leave the receptor alone, the receptor can do whatever it’s doing, but they significantly lower estrogen levels. So you’re kind of left in this ultra-low estrogen state. Again, the receptor is not going to be activated in that purpose. But resistance can happen as you heard in the previous talk.

And so we have really been building on this mechanistic understanding of the estrogen receptor. An older drug known as Faslodex, or fulvestrant, which is an injection, it’s an uncomfortable injection sometimes, as some of you have experienced it. What it does is, actually, when it binds to the receptor, it actually down-regulates the receptor and may actually destroy the receptor at some level. A lot of our newer drugs—some of them were referred to, and I’ll talk to you about it a little bit more—actually break down the receptor. So again, the mechanism is different, we’re trying to fool and trick these tumor cells with different biological understanding.

This busy slide highlights again that estrogen blockade is the principle mechanism where we treat hormone receptor-positive metastatic breast cancer, but it needs helpers often. These helpers actually target these additional pathways to help us further synergize. For example, the class of drugs known as the CDK 4/6 inhibitors, the names you would recognize are Ibrance [palbociclib], Kisqali [ribociclib] and Verzenio [abemaciclib]. They’re kind of like breaks; you are putting the breaks on tumor growth so the growth is slower and that estrogen blockade has additional time to work more effectively. These are very much a cornerstone of how we treat metastatic breast cancer, particularly in the first and second line.

The PI3K pathway, Dr. Tripathy showed some nice figures on that. This is an adjoining growth pathway and it can get revved up, particularly when an alteration is present. Those PI3K mutations that can be present in 30 to 40 percent of tumors. We actually have good drugs that we can use here. Several years ago we had the approval of Piqray, also known as alpelisib. And then in the last year, just since your last conference here, we have the approval of capivasertib, which is also known as Truqap. These are targeting PI3K inhibitors, and dozens of other PI3K inhibitors are under investigation.

Maryam Lustberg, MD, MPH [015:22]

Other helpers are PARP inhibitors. You heard about the kind of drugs that help capitalize on defects in DNA repair. These drugs can be combined with hormone therapy. So the principles here that I wanted to highlight are that we can work together to further strengthen hormonal blockade.

Immunotherapy. We are getting there for hormone receptor-positive breast cancer. We’re not quite there yet, but I think there’s exciting data that perhaps we can use additional strategies to make these what we call colder tumors, tumors that may not be as sensitive to immunotherapy, more sensitive to immunotherapy. So it’s coming, I feel hopeful but not quite ready for primetime.

A question I get asked by many patients who see me for treatment of metastatic breast cancer, and this may resonate with some of you, is “I want to do everything possible to make sure that I’m choosing the right treatment, that I’m improving my chances in the best possible way. Don’t spare me. Just give me the best recommendation.”

Sometimes when we talk about starting with endocrine therapy or hormonal blockade, a common question, and we welcome your questions kind of echoing the previous speaker. We want you to ask these questions. They ask, “Well, could it be that chemotherapy might work better? My friends and family are asking me why you’re not starting with chemotherapy.” And in breast cancer, we’re really fortunate that we have really well-designed clinical trials to inform our decisions.

In the last few years we had the randomized study called the RIGHT Choice study that was reported out. Patients with active metastatic disease were actually randomized to receiving chemotherapy versus hormonal therapy plus a targeted therapy like a CDK 4/6 inhibitor. And we can confidently and assuredly tell you that the ones that got hormonal therapy and targeted therapy, not only did they have good quality of life, but they actually had better cancer outcomes. So we’re not taking shortcuts when we’re recommending hormonal therapy and targeted therapy to you. It’s actually the better therapy.

When we talk about this diverse treatment landscape, and I know there’s a lot of questions on this because you want to again know what is the right treatment for you. We’re going to cover this a little bit here, but I think it may come up, it may be better elucidated during the question and answer. But the idea is the standard of care for that first-line metastatic breast cancer treatment is really a CDK 4/6 inhibitor plus endocrine therapy. We have data after data really showing that. Now as the early-stage metastatic breast cancer landscape is changing, there may be some patients who had a CDK 4/6 inhibitor even in that early-stage disease, and then they had unfortunately a progression. And so there’s also a lot of trials and agents looking at—for patients who particularly had unfortunately a quicker progression into that first-line metastatic disease—can we add additional targeted therapies such as a PI3K inhibitor or other targeted therapies that might help the next CDK 4/6 inhibitor work.

These trials, the closest one to getting approval, but it’s not approved yet, is listed on that top box. But more information is coming and there are a lot of clinical trials in that first-line space. After some time, and how long that time is is unique to you. We can’t predict what that time course looks like.

Many patients will need a second line of therapy due to progression, due to resistance that develops. And again, reemphasizing the point from the previous talk, it’s really important to understand the biology that is happening after progression. With the principle one, there are others too, but the really most important one being that estrogen receptor 1 mutation, the ESR1 mutation. Really, if you can take one thing away from this slide is that that second line therapy really, really needs additional biological information. And then, hopefully, you’ve also had germline testing so we know your genetic makeup. Because if you have a germline alteration such as BRCA 1/2 or PALB2, you actually are eligible for those targeted therapies as well.

Maryam Lustberg, MD, MPH [20:15]

At minimum, I would say what we want to know is: What is your PI3K status? What is your ESR1 status? And what is your germline mutation status? Now there are maybe additional alterations, but at least take away that much to ask your oncologist about.

There are a lot of trials in the second line space. So my second piece of advice here is if you have an opportunity—standard of care therapies are absolutely good—but if there’s an opportunity to also hit pause and also explore what clinical trial options are available in this space, it just gives you additional options of combining additional targeted therapies together and really having access to this next generation of drugs. And we can certainly talk more about that.

At some point, again I can’t predict when that would be for you individually, no matter how much I help block these estrogen pathways, no matter how many targeted therapies I add, at some point, unfortunately, most patients, the tumor may not care anymore how much we’re smartly manipulating estrogen pathways. And that’s when the role of chemotherapy comes in. And there’s no absolute standard in terms of what that first line chemotherapy should be. Although in conversation with many patients over the years after coming off a lot of oral-based therapies, generally the preference is can we try some type of oral based chemotherapy? And that would be capecitabine, which is quite active in hormone receptor-positive breast cancer. But certainly intravenous chemotherapy is an option as well. And certainly if there’s a clinical trial in that space near you, that would be something to consider.

Then after that, I think then we have this amazing opportunity to utilize some of our newest drugs, which include those antibody-drug conjugates that I told you. This is where we come back to how we’re bridging these different subtypes of breast cancer together. Enhertu, or trastuzumab deruxtecan, actually has an indication for HER2-low, hormone receptor-positive breast cancer. Amazing results. And similarly, we have an indication for use of Trodelvy, or sacituzumab, in the same population, whether you’re HER2-low or HER2-zero.

I believe Dr. Tripathy talked about this a little bit, but this HER2 status can be really tricky. So don’t be afraid to ask your oncologist, “Are you sure what my HER2 status is?” Because sometimes we really do need to look at this. And then many, many new drugs are coming, and lots of drugs that are targeting the estrogen receptor one pathway.

We have our first new endocrine therapy agent that was approved and that’s Orserdu, or elacestrant, for ESR1-mutated tumors. We have two approved agents now for PIK3 as I mentioned before, but more are coming. And then back to the mechanisms and how we understand the estrogen receptor.

Amazing scientists have thought of newer ways to target this estrogen receptor. One of the most promising ones is a class of drugs known as PROTACs, and that’s on the far left-hand side where you see the Pac-Man type figure. But this is really nifty. The idea is, let’s tag the tumor cells. Then our own internal machinery breaks down the tumor cells. Several PROTACs are in clinical trials, and it’s very active.

And then this is in no way exhaustive, but I did want to also highlight a class of drugs known as SERMs. So the idea we talked about breaking down estrogen receptor, these are complete estrogen receptor antagonists. They really block any functioning of the estrogen receptor. And this drug has been shown to be very promising. And I’ve listed the different clinical trials and combinations that are there.

So key takeaways is that estrogen receptor is a target, it is precision medicine. It’s one of our powerful ways. Let’s work together to incorporate some of these newer target targeted therapies on trial. And then traditional chemotherapy and antibody-drug conjugates, absolutely have a role and we need to work together to collaboratively manage side effects.

Maryam Lustberg, MD, MPH [24:55]

Moving on to HER2- positive breast cancer. I like to call these HER2, the HER family, as these transmembrane antennas. They’re little growth antennas that pick up signals from the outside and transmit further into the cell, amplifying the cell. And the discovery of Herceptin, or trastuzumab, which blocks this HER2 pathway has essentially also revolutionized cancer care for this set of tumors.

And these treatment paradigms can be a little confusing, but you saw some of the initial progression-free survival curves that Dr. Tripathy showed. As opposed to hormone receptor-positive breast cancer, where I made a big case that we don’t want to start with chemotherapy because it’s not the best option, in HER2 positive breast cancer we have really convincing data that if we initially incorporate some chemotherapy in combination with HER2-targeted therapy, we actually get a lot more benefit. So the idea is early incorporation of chemotherapy, then the chemotherapy falls off and many patients can essentially rest on Herceptin alone or Herceptin plus Perjeta is absolutely how we’re currently practicing.

Then second lines and third lines depend on a few factors. One is, is there evidence of involvement of the brain by breast cancer? So is there CNS [central nervous system] involvement of breast cancer?

We know as a class, patients with HER2-positive breast cancer have a higher chance of unfortunately experiencing relapse in the brain. So it’s important to report symptoms early if you’re having headaches or vision changes.

We have had several advances for patients with CNS involvement including the medication Tukysa, or tucatinib, which is an oral HER2 drug that has incredible penetration into the brain in ways that Herceptin does not. Because of an amazing study called HER2CLIMB we have that as an indication.

And then back to Enhertu. Enhertu also has actually really promising CNS activity as well. So in this second-line space, the way we think about it is you’re going to find some practice variation here, and that’s OK, but if there’s not active CNS involvement, generally the second line recommendation is for Enhertu. If there is active CNS involvement and your oncologist really wants to target the brain more actively, then certainly the Tukysa, Xeloda, Herceptin regimen is preferred.

After that we go into the realm of different drug combinations, including the older drug T-DM1, or Kadcyla, which used to be our second line. But then results showed that really Enhertu was behaving better in terms of clinical outcomes. So you are going to find that there are different variations in terms of how these additional drugs are sequenced and this is also an opportunity to also utilize clinical trials to gain access to some of these HER2-targeted drugs. I’m happy to take questions on those.

Trials to watch. We really want to investigate additional agents that have CNS activity beyond Tukysa. Before drugs are near approval they have funny long names and then they get cute names. So this is ZN-1041, which is currently in clinical trials. And then the second bullet highlights this principle of, even if patients don’t have a genetic alteration, a germline genetic alteration, they may benefit from the combination of a PARP inhibitor with HER2-directed therapy.

And then the third bullet I’m really excited about this trial. It’s from the Translational Breast Cancer Research Consortium. It’s called the SAPPHO study. Everything that I’ve shown you so far is about sequentially picking one therapy, using it till it stops helping us and then switching to the next line of therapy. Pretty logical. What the SAPPHO study is asking is let’s change that paradigm. We have all these active agents in HER2 positive breast cancer. What if we did them in rapid sequence? Essentially if we did active regimen one followed by active regimen two in sequence after a certain set interval, and gave a patient with HER2-positive metastatic breast cancer early access to all of these active agents. The question that they’re asking is: Are we going to have improved clinical outcomes and potentially disease eradication? So that’s exciting.

Maryam Lustberg, MD, MPH [29:57]

I know you guys heard about the STOP-HER2 study, but what I wanted to talk about there is how patient-centered it is. So the idea is patients who have been on HER2 targeted therapy for a long time, thankfully, do they really need to be on ongoing therapy or can it be right sized and potentially eliminated. And we didn’t want to decide that with a coin toss or a computerized randomized allocation. That just sounds ... A lot of patient advocates who were involved in the creation of this study said, “We don’t think patients would want that.” They wouldn’t want to be randomized to whether they received this therapy or not.

So this is extremely patient-centered, which is you get to decide which arm you go on. This is unusual as studies go. So you get to decide if you want to stay on your HER2-directed therapy and continue observations still contributing to the outcomes of the study. Or maybe you’re tired of coming every three weeks for the Phesgo injections or the Herceptin-Perjeta infusions. Maybe you need a break and you want to see how it is. Those patients can actually come off these infusions.

So very targetable pathway, we expect more HER2 antibody-drug conjugates coming. Thank you to all the companies who are working in this space and we also need to invest more in CNS metastasis. So I hope that work continues to expand triple-negative metastatic breast cancer.

By no way, we have been calling it that, that it doesn’t have targets, but that’s not true. That was just us not understanding that it has targets. It doesn’t have maybe the traditional ER, PR or HER2 targets, but there are actually multiple pathways including very much immune-mediated pathways that tend to be most activated in triple-negative breast cancer. So these tumors are most likely to benefit from our novel immunotherapy agents. A third of them are HER2-low, so that’s one of our targets. And also we don’t want to forget about germline genetics. A higher portion of patients with triple-negative breast cancer also have germline genetics. You do not need to have triple-negative breast cancer to have germline genetic testing. As you heard, all patients with metastatic breast cancer should have testing, but these are just multiple targets and many more are to come.

As we learn the biology of triple-negative breast cancer more are to come, but I think one of the most exciting areas is related to immunotherapy. We have approvals right now for the immune checkpoint inhibitors like pembrolizumab, but lots of exciting work with cancer vaccines and adaptive cell therapy. And I will highlight those. But I just wanted to kind of take you back toward a history lesson of the timeline, which is that in many ways breast cancer was a late comer to the immunotherapy landscape. The second box highlights the approval of pembrolizumab, or Keytruda, in combination with chemotherapy. And then I wanted to again bring this back to the theme of tumor agnostic indications. Tumors that have high mutational burden actually can have an indication for immunotherapy regardless of being triple negative or not, it doesn’t matter.

But back to this kind of idea of can we harness the immunotherapy option to better target these tumors. And back to drug development technology. I’m not a drug developer, but really incredible work has gone into improving the technology of how we harness and create these chimeric antigen receptors which become tools to essentially individualize the T cells that are harvested. We isolate T cells from you, and then really activate and expand them so they’re precisely going after the tumors in your body that have these targets. And this is no longer science fiction.

This particular schema is from a trial that we have ongoing at Yale right now with Dr. Hurwitz, who’s the PI. But there’s lots of trials like this looking at CAR T production and infusion. This particular trial is specifically for triple-negative breast cancer and the target that it’s looking for. Back to the theme of we need targets identified that maybe we weren’t thinking of. It’s looking at this receptor tyrosine kinase orphan receptor that’s expressed in a lot of triple-negative breast cancers. And so this is the trial from Yale. You may have things closer to you as well.

This is in no way saying we are the only ones that are doing this work. But the principle is creating your own specialized targeted immunotherapy infusion that goes after your tumor cells. There are certainly limitations in that it takes time to engineer those T cells to be precise. And so there has to be a lot of thoughtful attention in terms of when we are actually utilizing this approach because if your liver is progressing, we don’t want to take four to six weeks to do this. What I advise you, if you’re in that first or second line in your triple-negative breast cancer care, that’s the time to start exploring these clinical trial options. So you can plan. You don’t want to wait until that third progression or later to be planning, because by planning ahead you can potentially find these options and really be thoughtful with your oncologist about when to incorporate them.

Maryam Lustberg, MD, MPH [35:59]

To cover the Midwest portion of the country. Again, this is from my colleague, Dr. Maggie Gatti-Mays in Ohio State, which is the idea again of tumor cells that are expressing a certain protein, GD2, and then kind of essentially infusing these natural killer cells. And this is an early phase study and it’s currently enrolling. So just options to keep in mind, and there are many others you can explore closer to you.

Antibody-drug conjugates are absolutely part of how we’re treating triple- negative breast cancer with the first indication being Trodelvy, sacituzumab, as part of the ASCENT study. And then later we had the approval of Enhertu in the setting of triple negatives that are HER2 low. But lots of exciting trials are in the horizon including things that we call biphasic antibodies. And the idea is instead of just targeting the tumor cells, that there’s actually an adjoining antibody target that is also targeting the T cell. So it’s like this dual approach synergy to go after and then start this cascade of immune activation along with the release of chemotherapy. And we think this could be a really attractive option in trials to come in triple-negative breast cancer. So lots of innovative ADCs are in the horizon.

And then kind of wrapping up with HER2 low, just reemphasizing that many of you will have, regardless of your subtype of breast cancer, tumors that are HER2 low. Make sure you know your HER2 results. And the most important bullet that I can highlight is that HER2-low status can even be from that primary, original early-stage breast cancer tumor. Even if your current metastatic tissue biopsy is showing a HER2 score of zero, or if you had early-stage breast cancer at some point, even that early stage breast cancer counts. Just by having HER2 low at any point, at any tissue, you qualify for Enhertu.

This is also when you question your oncologist and they’ll be really impressed. So the question is, there is a ton of data that HER2 testing is really fraught with error. We’re not trying to mislead you. We’re doing the best we can, but what has been shown is that pathologists can have a really hard time knowing what’s zero, what’s HER2 low. And we may be depriving some patients who are, we’re calling HER2 zero, but they may be HER2 low. So this is where you ask your oncologist: Can you retest my tumor? Can you maybe send that out or use other methodologies to test for HER2? Those are good questions to ask.

We’re almost at time for the talk portion, but I want to address many unanswered gaps which apply to all subtypes and that includes sequencing of therapies.

A lot of active work is being done in terms of which drug should I use first. So you’re going to see a lot of information on this coming up in the coming years.

Dosing. We really need to optimize our dosing. The FDA has listened, and this has been because of efforts of patient advocates, I really want to emphasize that. The Right Dose Organization has a booth here and I had the fortune of acting as one of their advisors. And we lost a visionary leader of the Right Dose, Anne Loeser, last year who tirelessly advocated that the maximal tolerated dose may not be the right dose. And that these questions need to be asked.

Happy to take questions on oligometastatic disease. This is a fancy way of saying that when you have a few spots of disease as opposed to multiple spots of disease, current paradigm is that we still think you benefit most from just treating the whole body and not doing spot control, like not cutting things out or giving focal radiation. But the NCI is also paying attention because maybe, maybe we were too simplistic and additional studies need to be done, particularly in patients who present with stage IV de novo disease. So more trials are needed there.

Maryam Lustberg, MD, MPH [40:28]

And beyond the scope of this talk, but I also actively research how can we all work better as a team because cancer care is quite complicated and we really need holistic care. Brain mets please, to the sponsors who are listening, we need a lot more activity in this space. Lots of unmet need.

If you are being offered the choice of whole brain radiation. My takeaway for you is make sure you’re getting a second opinion from a brain breast medical oncologist and radiation oncologist. Because what we’re going away from is we want to use less whole brain and to more targeted therapies systemically or to more focused radiation.

We need to work on continued expanding of our trial eligibility and we need more targeted therapies.

I talked about this already, and my last slide is this, which is, I know the metastatic breast community is mourning today. They’re quite shocked by our recent losses. And I just wanted to say I hear you, and in no way do I want to pretend that everything is OK, because everything is not OK. We are making progress, but it’s not happening quickly enough. And I do get a sense that things are accelerating, which is good in terms of progress. Mortality is coming down, it needs to come down faster and go to zero.

And then I wanted to draw your attention to another area of unmet need, which is that flat line at the bottom. This is the incidence of de novo stage IV breast cancer. This is patients who present with stage IV breast cancer that no imaging was able to detect the primary breast tumor or they didn’t have access to those early-stage imaging data. So it’s not their fault, it’s that their disease presented at stage IV. As you can see, we haven’t made a dent in that at all. So in the future, I think more innovative, blood-based monitoring studies at a population level may be the answer there, but lots more research needed there. So I hope I’ve cleared a little bit of the cloudy picture.

This is my favorite sunrise in the Haleakalā National Park in Hawaii. And thank you. Thank you for your time.

Jean Sachs, MSS, MLSP [43:09]

Thank you so much. That was great. More complications, but I’m sure the questions are going to come in super quickly. So Ashley and Katie are going to help me, but I just thought we could start. There’s a couple people that say these new drugs are great, but they’re expensive and sometimes insurance companies will pay for infusions and they won’t pay for oral. I know you’re not a payer, but just any insights on how we get the insurance companies to catch up with the rapid pace of science.

Maryam Lustberg, MD, MPH [44:40]

Yeah, it’s absolutely a huge problem and I think you’re raising the financial toxicity that impacts the lives of our patients living with all cancers, including metastatic breast cancer. I think it comes down to advocacy.

I’ve been so impressed with what the metastatic breast cancer advocacy community has achieved in recent years. And I think, as many of you know, most recently there was the ASCO [American Society of Clinical Oncology] advocacy meeting in Capitol Hill and a lot of the focus was on drug shortages, which is another whole area.

But I do think banding together and highlighting that this is a critical need. Then also working with industry sponsors to have better patient access programs. I know they do a lot, but there are patients that are in that middle income space, who don’t always qualify. My message to them would be, I think sometimes some of the income cutoffs are, are leaving a large group of patients who are at significant hardship. So I think it would have to be some type of a forum and continued efforts between policy makers, industry sponsors, patient advocates and oncologists. And I’m sorry I don’t have an easy solution.

Jean Sachs, MSS, MLSP [45:10]

No, that’s, I didn’t expect you to, but I think it’s really important that we talk about it because we know oral medications have value, it keeps people out of the hospital, out of the doctor’s offices. So we got to get the insurance to continue to pay that. OK, Katie.

Kathryn Edick [45:24]

There are a few questions about clinical trials in general. A lot of people want to know when they should, and why they should, access a clinical trial. Do they do that at first line treatment or should they wait?

Maryam Lustberg, MD, MPH [45:40]

Great question. Thank you for asking it.

I just want to re-highlight that every treatment that we currently have as standard of care was previously tested in a clinical trial. So brave individuals before you participated in these clinical trials and made these available. Two, so much safety and consideration is given to clinical trials that some studies have actually shown that patients on clinical trials can actually have better outcomes. There’s multiple watches on them and they get access to the newer drugs.

But to more principally answer your question, I would say at every juncture, I think it’s important in that discussion with your oncology team to ask the question, what are my standard options and what are my clinical trial options? At that juncture it may make more sense to do a standard of care therapy or it may make sense to do a clinical trial. We no longer, or we never really, recommend you waiting until you’re on your third, fourth line or fifth line of metastatic breast cancer treatment to consider clinical trial. Really at every juncture, whether it be first line, second line, or third line, at least ask the question so you know your options. And then depending on, clinical trials have both pros and cons and we don’t want to minimize the cons, but I think the cons can be sometimes an additional time commitment or a larger commute depending on where you’re living. All that can be considered together to really decide on what the right option is. So don’t wait, I would say ask at every juncture,

Jean Sachs, MSS, MLSP [47:19]

Right. And the why is clear. We’re only going to get new drugs and hopefully cure this disease if people participate.

I was so struck by the de novo slide. And there is a question here from a new young de novo metastatic person and she’s asking, do you think lowering the age of routine imaging would improve this downward trend. Do you think it’s imaging or do you think that it’s a different kind of screening?

Maryam Lustberg, MD, MPH [47:44]

I appreciate your question and I think it’s one of the central research questions. The truth is we don’t know fully that answer. I think it really is continuing to be researched, but I would say it’s twofold. One is that we are not, in general, widely doing what we call risk assessment. We were using that cookie cutter approach—start at age 40, get your mammogram—and we may be missing opportunities where groups that need to start younger or may have additional risk factors that really necessitate them having breast imaging sooner are being missed.

We’re moving toward incorporating these risk-based calculators. Every woman should really know her risk of breast cancer. And there’s also some concerns that perhaps with certain populations like Black women, again, a lot of these studies were done on white women and that led us to identify these certain age cutoff points. Should we have really more personalized recommendations in terms of how we do imaging?

But I don’t think it’s all about imaging and the reason for that is in some of these de novo breast cancers the process may be simultaneous, where it takes one cell in the tumor cell and by the time that we’re actually able to see it in a breast imaging, it may already have those extra invasive properties to spread to the rest of the body.

This is my opinion, it may not be shared by others, but it’s that the field of blood-based population-based monitoring is currently under great study. You heard a little bit about liquid biopsies in terms of, you know, taking patients who already have cancer and using the blood to understand what’s going on. But then there’s a separate whole field of blood-based monitoring where there are large scale population studies asking the questions. Can we identify early signs of cancer in the blood before we can even detect it on imaging? Those studies are ongoing. I don’t recommend that we run and do them now as standard of care. But to answer your question, I think it has to be a combination of more personalized risk assessment plus kind of better blood-based monitoring.

Kathryn Edick [50:15]

Thank you. I’m going to take us back to clinical trials again. I think then there’s also more conversation about when we talked about when, why, but how. How do people who are in rural communities or who are going to community hospitals access these clinical trials? And then, part two of that is people are questioning if you’ve been on so many lines of treatment, then you may not be eligible for clinical trial.

Maryam Lustberg, MD, MPH [50:42]

Great question. So maybe I’ll take the second part first, which is that it is true that trials do have specific eligibility criteria and it sometimes drives us crazy, even us oncologists because they can be sometimes too strict and too limiting. There’s a whole other advocacy effort going on in terms of making eligibility criteria more flexible and opening doors for more patients.

In terms of prior lines of therapy, it really depends on the clinical trial. Some would say you can only have had one or two lines of therapy, but not all of them, particularly for example, phase I trials, which generally do not restrict the prior lines of therapy. What they base eligibility on is how good is your performance status, how well are you functioning in day-to-day life, what your kidney and liver function tests are looking like? And a lot of them are now focusing on a certain biomarker. So back to our theme of biomarkers and targeted therapy. If you have that particular target, then that’s part of the eligibility. So yes, I think prior lines of therapy may exclude you from some trials, but not all.

In terms of access to clinical trials. It’s a huge area also of unmet need. We do know that patients who are near academic, tertiary type settings tend to have sometimes more access to clinical trials, whereas patients in communities and in the community oncology setting may have less, but that’s not always the case. But particularly the rural areas are quite at risk of, even if they want to, sometimes there’s weekly visits for some of these trials, not all of them, and so to have to commute a long way. I think what we’re trying to do is the concept of decentralization of clinical trials, which is that we don’t, most patients are treated in the community and we do not want to be only focusing on this narrow group of patients who are near tertiary care centers.

There’s this whole effort on bringing more clinical trials to the community. We’re not fully there, but I think at least our field is taking attention that this is not good the way it is. So more efforts on that are coming.

In terms of finding a clinical trial that’s eligible for you. One is talking to your oncology team. Two is several advocacy organizations have actually put together resources in terms of clinical trial lists and availabilities. And three, I believe patient advocates are sometimes astonishingly knowledgeable about the availability of clinical trials. So kind of connecting to advocacy organizations would be my central advice.

Ashley Dedmon, MPH, CHES, LSS [53:46]

We have questions around biopsies. This is a two part question. Can HER2 be tested through liquid biopsy? And the second part is do bone biopsies give as accurate results about receptors as a tissue biopsy?

Maryam Lustberg, MD, MPH [54:03]

Such a great question. I’m so glad you asked that.

So bone tissue can be some of the most challenging tissue to do reliable testing on, particularly HER2. The reason for that is you can imagine that bone tissue is hard and they have to decalcify it, take some of the calcium out in order to run the protein staining. If that’s the only site of disease you have, absolutely it’s important to still biopsy bone, but knowing its limitations and knowing that if in the future there is an additional site to biopsy to not forget to do that because bone can be unreliable in some ways.

But the first part of the question was really important in that it came up also in the session before me about the differences between liquid biopsies and tumor tissue biopsies. And that’s the one difference with liquid biopsies is that we don’t get the HER2 status. It will give you HER2 mutations but not HER2 expression, which is what we need for indications like for Enhertu. That’s what I was hoping to also address from the previous session is that if there’s any question about HER2 status, the liquid biopsy will not be enough and we would recommend a tumor tissue sampling.

So for a patient who, let’s say was HER2 zero, or I’ll give an example. I have a patient who just recently started a CDK 4/6 inhibitor, hormone receptor-positive breast cancer, and her scans at 11 months unfortunately are showing evidence of progression. And it’s a little bit earlier than we think of on average. Every person is unique, but in this case, yes I could send a liquid biopsy because I’m checking for ESR1 status. But I actually talked to her and I said, this is the case where we really need to look at your tissue again because I want to feel confident about this HER2 status. Because when tumors don’t behave exactly as you’re expecting, that’s another sign that maybe we missed the HER2 signal initially. So I think if there’s any question about HER2 status, go for the tissue and not the blood.

Jean Sachs, MSS, MLSP [56:19]

So I think this would be good to address. We know that Orserdu was approved if you have the ESR1 mutation. So this person is saying, well if I do have the ESR1 and I take this new therapy but it doesn’t work, are there other similar SERDs that are available. And of course I’m going to add and do you really need the ESR1 mutation to get access to the others?

Maryam Lustberg, MD, MPH [56:44]

Great question. The EMERALD study, which was the study that led to the approval of Orserdu actually included patients with and without ESR1 mutations and benefit was seen in both. When the FDA was reviewing the data, the benefit was strongest in those who had mutations in the ESR1 pathway; that is why it led to that indication for now. On standard of care right now, the only way we can give you Orserdu is if the tumor has an ESR1 mutation.

However there are multiple clinical trials that are investigating different SERDs and even elecestrant, or Orserdu. There is the ELEVATE study that is being run by that company which is actually combining Orserdu with other targeted therapies. So the question of access comes to that second or third line space where I really encourage you to explore your clinical trial options because it will actually expand your options. So definitely take a look.

And yeah, definitely other SERDs are absolutely being investigated but as standard of care, essentially that’s what we have right now.

Jean Sachs, MSS, MLSP [58:01]

Yeah, and that’s a good example of patient advocacy. because at the San Antonio breast cancer meeting this year, there was an FDA panel and the metastatic advocates were really angry that the non ESR1 group that did do well were not approved. Again, they really let their voices be heard.

OK, go ahead Katie. I’m sure you have another question.

Kathryn Edick [58:23]

Yeah, so I’m grouping some together again. There’s lots of questions around the standard of care. Specifically, you talk about HER2 positive every three weeks, people are questioning if there are studies or can it be stretched to four weeks or longer out? And the same is for other medications that are oral where you take them for five days and then you have like a week of rest. There’s just these questions about stretching with that. I think if I’m understanding quality of life, but also to decrease resistance during those rest periods.

Maryam Lustberg, MD, MPH [59:00]

Great question. I think it comes back to optimizing dosing, which I highlighted as an unmet need.

In terms of whether changing dosing helps us overcome or reduce the risk of resistance, as far as I know we don’t have good data for that approach, but there are other reasons to explore alternative dosing and that could be quality of life issues and vacations.

I’m all for trips and vacations. I’ve had patients who stretch their Herceptin and Perjeta to every four weeks, for a period of time. I think it really comes down to that shared decision making and sharing with them. I don’t have official data to tell you that every four weeks is no different, but it’s probably OK for a short period of time, especially if the disease has been stable for a long time.

We do have some data on alternative dosing regimens, though, that I feel extra confident for. For example, with capecitabine, many of you may know that it’s two weeks on, one week off, but we actually have published data that the one week on, one week off regimen and making it a four week cycle, actually is equally effective and often is associated with less toxicity. That one I would feel even extra confident about because I can point to a published paper.

In terms of dose reductions, and I know that wasn’t part of the question, we actually have a ton of data on our targeted therapies showing that dose reductions in targeted therapies do not negatively impact outcomes. So don’t be afraid to use dose modifications when you need it.

But for these alternative dosing schedules, I would say look at your life, look at your needs, really work with your oncology team, and don’t ever sacrifice a trip.

Jean Sachs, MSS, MLSP [1:00:54]

And I would add, talk to each other. I know there’s a lot of closed social media pages with people on the same drugs. A lot of you have gotten very creative with your oncologists and found dosing schedules. Again, these new drugs are new, so we don’t know that much like we do about some of the older drugs. So I think it’s really important to learn from each other. Go ahead, Ashley.

Ashley Dedmon, MPH, CHES, LSS [1:01:17]

There’s one follow up question, from our last question. How much latitude do doctors have in diverging from standard of care?

Maryam Lustberg, MD, MPH [1:01:27]

Like there’s no one, same patient, I would say there is quite a bit of difference among oncologists, and some of us are more rigid than others.

I think back to hearing from patients and patient advocates, I feel like, as a field, we’re coming around more, in terms of being a little bit more flexible. I believe you made that point, Jean, the idea of making sure it’s a right fit with your oncologist. Some are going to be more by the book than others I’m not going to sugarcoat that. But then there are others who really enjoy the creativity of working with you and coming up with new solutions. And I just love those conversations because it really highlights that partnership aspect of oncology care.

I think there’s variability there, and if you want to interview your oncologist, that could be one of the first questions you ask them. And that has helped me a lot, in these first visits I ask my patients a few key questions, which are: How do you want our communication to be? How do you want your scan results? Do you want them released? Do you want me to call you? I don’t want any surprises in terms of what their preferences are, but understanding and it’s a relationship just like anything else. And you need to know what your preferences are.

Jean Sachs, MSS, MLSP [1:02:57]

Yeah, that’s a good point. I mean, now that they do release records, I think it’s within 12 hours

Maryam Lustberg, MD, MPH [1:02:02]

Or sooner.

Jean Sachs, MSS, MLSP [1:02:03]

Or sooner.

But you can tell your hospital or your healthcare provider, I don’t want them released. I want a phone call. You just have to make that known.

There’s an interesting question. I don’t know how you’ll answer this, but I think the question is: Is de novo metastatic breast cancer more aggressive than progression? Or is it really just about the subtype?

Maryam Lustberg, MD, MPH [1:03:28]

The answer is we think it’s not more aggressive, interestingly. My colleague is Dr. Lajos Pusztai, who is the co-chair of the SWOG breast committee. And there is an editorial in the Journal of Clinical Oncology. If you just look up, his name is a little complicated, we can release it. But essentially he presents a really compelling argument that de novo breast cancer that hasn’t been through other treatments and different clonal evolution. Actually one of his big, big points that many others support, including myself, is that in some ways, in a lot of our metastatic trials, we couple stage IV and metastatic breast cancer as if it’s one population. But in many ways, this de novo population has, one, different needs, may have slightly different biology, and that this is the population that actually the National Cancer Institute will likely, it’s not official yet, will likely be focusing on in terms of that oligometastatic curative intent.

Jean Sachs, MSS, MLSP [1:04:35]

That’s so interesting. Because you’re not pretreated. I know, for the patient, it’s much more difficult because they don’t have a team in place and this is also new to them.But that’s reassuring and I would love to know more about that.

Kathryn Edick [1:04:50]

We have a couple questions around the oligometastatic field. First, how do you classify how somebody is oligometastatic? And then the second part of that is, do you recommend mastectomies for your de novo or oligometastatic patients?

Maryam Lustberg, MD, MPH [1:05:08]

Great, thank you for that question. The definition of oligometastatic disease can vary across trials, but most of the trials have used the cutoff of four or five distant metastatic sites as the cutoff. Generally, most of the trials that have studied this in breast cancer have really focused on patients who have maybe up to three distant metastatic sites or even one. But the official definition of oligometastatic is five sites or less. And this is the dilemma with oligometastatic disease.

When we’ve had large scale studies in breast cancer, for example, we had a trial that looked at all comers in terms of metastatic breast cancer. They may have had primary breast cancer that became metastatic disease or they were de novo stage IV. And they asked the question: What if we do mastectomy or some type of breast surgery in addition to systemic therapy or only systemic therapy. And what that trial showed is that there was no difference in outcomes and it didn’t help patients live longer.

So in general— there are always exceptions, but in general—if we’re following evidence-based practice, the role of local therapy for this oligometastatic disease has not been shown to be clearly beneficial. Now, there are always exceptions. There’s always one oncologist or one patient or maybe somebody here who will stand up and say, “I had this and I’m doing well and I’m disease free,” and I’m so happy for you because there are always exceptions to these rules and humans are individuals and unique. But at least our phase III breast surgery trial did not show a benefit.

We’re a bit cautious about this approach because often if you take time for local therapy, that period of healing that you need from surgery is that whole time that I’m not able to give you effective systemic therapy that’s treating the body. And sometimes we can see that additional sites may develop, et cetera.

In terms of local therapy with radiation, or if we have one or two liver spots, can we go cut it out or radiate it? There have been several studies that have asked that question in breast cancer. And again, what they have shown is that it works in lung cancer. This is going against my initial tumor agnostic discussion. It works in lung cancer when we go in, zap, zap, zap. But it doesn’t work with breast cancer. And we don’t know exactly why. But the thought is twofold. One is that breast cancer may be more of a systemic disease and I can zap what I can see, but I’m not eradicating some other hidden things that I’m not seeing. But the second thing is, back to is it de novo. These trials had heterogeneous populations of de novo and metastatic cancer and did that muddy the waters?

I think we need more data, but what I’m telling my patients is even if you have oligometastatic disease, absolutely start systemic therapy first. Let’s see what the disease trajectory is and then have additional shared decision discussions.

Jean Sachs, MSS, MLSP [1:08:26]

I’m going to change the focus just a little bit. Some people are saying, what’s your opinion about adding some kind of naturopathic doctor or adding other complimentary therapies? And do you ever work with those providers or sort of what do you tell your metastatic patients?

Maryam Lustberg, MD, MPH [1:08:46]

It’s a great question. I think in some ways, back to how rigid the oncology field has been. In some ways we’ve been rigid; in some ways we’ve had a right to be rigid, in that some of these herbal and supplements can actually have adverse effects and actually counteract negatively with our cancer therapies. And part of it is because we’ve been such polarized specialties, the naturopaths and the regular oncologists have not been sitting at the same table having these discussions. It’s been these silos that have developed.

What I share with my patients is that ultimately they’re the decision maker. I’m the guide. I will share with them when we don’t have data on combinations, and that I may have concerns. I share with them that I don’t want them to be afraid to tell me if they want to explore these options or use these options because it’s much safer for me to at least know what they’re using. It’s not something that I would recommend on my own. But I have dialogues with my patients, because a lot of assertions are made about some of these therapies without good, randomized data. And we have seen so often that something that works in a cell line or in an animal model is not how these agents are behaving in humans. So I would just recommend open dialogue and exercising caution.

Ashley Dedmon, MPH, CHES, LSS [1:10:17]

Given the incidence of de novo, should the guidance be that all persons start out with breast MRIs or ultrasounds regular imaging versus mammograms, especially dense breast tissue persons?

Maryam Lustberg, MD, MPH [1:10:34]

It’s a great question. We thankfully have very much learned that it’s every woman’s right to know that they have dense breast tissue.

Dense breast tissue is important twofold. One, it elevates the future risk of breast cancer on its own as a biological factor and then it also can make imaging by mammography more challenging. So if your family members or siblings or children have dense breast tissue, make sure that they’re aware that it’s their right to complement mammography screening with ultrasound. I think that’s an important thing.

The role of MRI is that it’s a great test for patients who have a higher than 20 percent lifetime risk of developing breast cancer. But it also has limitations. One is that it’s highly sensitive, which is it can see every little thing, but it’s not very specific. So it can lead to a lot of false positives where patients end up getting scar tissue and multiple biopsies and things like that. So this is something you can take back to your loved ones. You need to know your risk for breast cancer. If you are average risk, then the MRI may actually do more harm than good, but certainly ultrasound complementing mammogram for breast dense tissue.

Jean Sachs, MSS, MLSP [1:12:03]

This is a question I was hoping you would address, which is that now that we’ve had three CDK 4/6 inhibitors on the market for a while, are they starting to be like, if you try one and either it fails or you have a hard time with the side effects, are you starting to move patients to different ones?

Maryam Lustberg, MD, MPH [1:12:23]

Great question, yes. We have three approved agents. The first one was Ibrance, thank you Pfizer. And I remember the day I started using Ibrance because it completely changed how my patients were doing. They could stay on therapy for years and years and years and it was amazing.

Now that we have Kisqali and Verzenio, if we go strictly by evidence, phase III, evidence level data, only Kisqali has been associated with significant overall survival data. And so you’re going to find some practice variation among oncologists, but I think by the strength of overall survival data, there is a tendency to more likely to start with Kisqali at a first line. But I have done that and many a time I do end up switching for various reasons due to toxicity. So it is absolutely possible to switch among agents.

Your second question about resistance and progression beyond CDK 4/6 inhibitor, I’m glad you brought that up. In patients who experience a progression of their disease on a first line CDK 4/6 inhibitor, they have lots of options. We talked about that big figure with lots of options, but let’s say there is not a clear genomic alteration target to go after. We actually had a study that was reported by Kevin Kalinsky called the MAINTAIN study that showed that switching your endocrine therapy backbone and then switching your CDK 4/6 inhibitor actually had some effect. So it is an option.

Kathryn Edick [1:14:05]

Yes. There are questions out there because we have the STOP-HER2 trial, so people are inquiring about other mutations and ER-positive if you have been NED, are there any other trials out there or any thoughts about discontinuing or stopping treatment for other subtypes besides HER2?

Maryam Lustberg, MD, MPH [1:14:31]

Great question. I think it probably most next applies for … no it really does apply to other subtypes. I’ve been doing this for 20 years and I’ve definitely experienced patients across all subtypes having long-term disease stability. For hormone receptor-positive breast cancer, it comes down to toxicity. So if, for example, the endocrine therapy agent is causing other long-term effects, effects on bone health and things like that, I think it’s really an individualized and shared decision making where we don’t have a trial and probably that trial will never get done unfortunately. But it is an opportunity to think about, is it causing more harm than good. And I think it could be a decision that you make with your oncologist, but there’s no trial that I can refer you to for that.

In terms of triple-negative breast cancer patients. I’ve had patients who’ve had long-term disease stability on immunotherapy and then we had this discussion of do we stop immunotherapy or keep it going. And it’s different patients choose differently and it’s OK. It’s OK. But it is a data-free zone

Jean Sachs, MSS, MLSP [1:15:53]

We only have a few more minutes anyway and I’m sure everybody wants to have lunch. I would just love to ask you, what are you most excited about? There’s clearly a lot of things in the works. It’s also, I think for patients, getting really confusing between all the additional testing and the new therapies. Are you feeling like this is the way it’s going to go, we’re just going to get more and more personalized in how we treat breast cancer?

Maryam Lustberg, MD, MPH [1:16:23]

I think the antibody-drug conjugates are going to completely transform oncology care. I see that space rapidly changing in the next few years. So I’m very excited about that. The second thing that I’m excited about is that the whole field of circulating tumor DNA, both in early stage as well as advanced disease, I think we’re just in the beginning, I think for this idea of using our blood as a way of more closely monitoring and personalizing therapies. And the third thing I’m excited about is what the advocacy community is achieving. I feel really honored, I really think you guys have improved care and how we deliver care. So thank you to all the advocates who are tirelessly working on this.

Jean Sachs, MSS, MLSP [1:17:29]

Yeah, and also for the oncology community for being open to let patients in, because patients are sitting on IRBs and clinical trial review and study design and patient materials and really listened to. And you talked about what—Sheila I knew for many, many years, and that was what she made such a difference on. So we just appreciate the compassion of the breast oncology community.