Innovations in care: What you know matters

This four-part series features discussions that help individuals further understand their options by providing insight on breakthroughs in treatments, the role of testing, and navigating the cost of cancer care.

The sessions empower both those diagnosed with early-stage and metastatic breast cancer to make informed decisions about their care and provide strategies to help them advocate for themselves throughout treatment and beyond.

Session 1 | Shared decision making and patient choices

Speakers: Blakeley Schmidt Anderson; Don Dizon, MD, FACP, FASCO

Moderator: Amelia O'Relly

In this age of personalized medicine, treatment decision making can be a complex matter. This program helps you understand why there are standards of care in breast cancer treatment, how they impact your treatment decisions, and how to advocate for standard of care if you think you are not receiving the care you deserve.

Watch or listen to the recording below, or read the transcript here.

Session 2 | Innovations in treatment and side effect management

Speaker: Eleonora Teplinsky, MD

Learn about the latest breakthroughs in targeted treatment, how these treatments are administered, the short-term and long-term impacts of chemotherapy and strategies for managing these side effects. We also explore the evolution beyond chemotherapy, oral therapies that may make treatment more convenient and ways that personalized medicine may impact your treatment plan and provide you with options.

Watch or listen to the recording below, or read the transcript here.

Session 3 | Understanding testing in breast cancer

Speaker: Reshma Mahtani, DO

This session explains the role of testing in breast cancer today. Learn about the tests that look for mutations, or changes, in tumors and in the blood and are used to develop a tailored treatment plan for your personalized care.

Watch or listen to the recording below, or read the transcript here.

Session 4 | Practical matters: The financial and time toxicity of breast cancer

Speakers: Erin Bradshaw; Pallav Mehta, MD

Moderator: Kelly Choy-Wilson

The term financial toxicity describes both the practical and the emotional impact of the cost of care on individuals and families managing a cancer diagnosis. This session explains the factors that contribute to financial toxicity, explores their impact, and provides ways to reduce or overcome obstacles. Hear about useful resources to assist with everyday bills, manage costs, and eliminate barriers to quality healthcare.

Watch or listen to the recording below, or read the transcript here.

Transcripts

• Session 1
• Session 2
• Session 3
• Session 4

Session 1 | Shared decision making and patient choices

Amelia O’Relly [00:00:07]

I am honored to introduce you to today’s exceptional speakers.

We have, first of all, Dr. Don Dizon, a medical oncologist who’s a professor of medicine and surgery at Brown University, director of Pelvic Malignancies and Lifespan Cancer Institute, and the head of community outreach and engagement at the Legorreta Cancer Center at Brown University in Providence, Rhode Island.

Joining Dr. Dizon is Blakeley Schmidt Anderson. She is a patient advocate who was diagnosed, also in 2019, with early-stage breast cancer. Blakeley is a patient of Dr. Dizon, and both of their bios are also on LBBC.ORG.

Welcome, Blakeley and Dr. Dizon, and thank you so much for joining us today.

Don Dizon, MD, FACP, FASCO [00:00:50]

Thank you for having me.

Blakeley Schmidt Anderson [00:00:52]

Thank you for having us.

Amelia O’Relly [00:00:54]

Dr. Dizon, I’d like to start off with you first, just to give us, if you would, please, a little bit of context for our conversation. I’d like to start by having you give an explanation of personalized medicine and standard of care and what that really means.

Don Dizon, MD, FACP, FASCO [00:00:50]

This is a concept that’s been with us now for at least 8 years, even 10 years, but it’s the notion that cancer is not just this one monolithic disease and that even breast cancer isn’t one disease that requires a cookbook recipe to treat.

We know that breast cancers come in different forms and the ones that people have most likely heard about, hormone receptor-positive disease; triple-positive disease, which is hormone receptor positive, HER2-positive; triple-negative disease, which is negative for hormone receptors and does not express the HER2 protein; and then there’s ER-negative, HER2-positive disease.

All of these four very basic forms of breast cancer require their own treatments. But even now we’re learning that within each of those four groups, there are little subgroups that may require even more diving deeper to figure out what the tumor is. If you just focus, say, on hormone receptor-positive disease, people are now getting tested for what’s called the recurrence score, or they may be going through an assay that will indicate based on the tumor DNA, what are the chances that it could come back. In fact, they may get a prognostic score of, say you took tamoxifen alone, based on the tumor DNA this is the chances it could come back, if you took just tamoxifen. And we’re morphing these figures and trying to see, does it only work in small tumors or does it work in large tumors. Does it work if the lymph nodes are not involved, or does it work when the lymph nodes are involved? And this is the emerging science, but all of these questions are leading us towards a time which we are now in, and hopefully we’ll get better, where we can now look at someone with breast cancer as opposed to just looking at their cancer and helping them decide what are my options and what do we think is the best course of action now? Now that’s really the goal.

Amelia O’Relly [00:03:35]

The conversation around treatment decisions for providers and for patients that then kind of melds out of this notion of the standard of care is more individualized. It’s becoming more individualized over and over again. Thank you for that.

Blakeley, I’d love for you to tell us a little bit about your story, and as part of that, to the point we were just talking about, we’d love to, to kind of hear how you’ve also been able to make your own treatment decisions alongside Dr. Dizon. So tell us a little bit.

Blakeley Schmidt Anderson [00:04:14]

I found a lump at the beginning of October 2019 while I was getting ready for work one day. It was just a regular day, and I was like, I’ve gotten dressed a lot of days and put on my bra a lot of times and this just doesn’t seem right. I went to my doctor, wound up with a mammogram and diagnostic ultrasound, and then was diagnosed by the 31st of October.

I got very lucky. I was 36. Nobody blinked twice about me being as young as I was, but again, I recognize I got very lucky because that’s not everyone’s experience. I live in Rhode Island, and I immediately went to the hospital in Providence where Dr. Dizon works and met him. I also did decide to get a second opinion because I am someone who wants as much information as possible. And then I made my choice.

I was aware of standard of care. Standard of care is a very obscure word and phrase for most everybody. My background is medical health education. I had that in my background, so I was a little bit familiar with what that meant. So going in, I had, I’d say a toe up, but that’s about it because I have learned so much since. I got a second opinion and learned what my tumor was. I was HER2-positive, I was ER-, PR-positive, but those percentages were very low. My tumors were ER-, PR-positive, but less than 10%, which when we start to talk about personalized medicine and personalized choices all of those details really play in.

That’s my story. I did about five and a half months of neoadjuvant chemo, chemo before surgery, because, which, of course, that terrified me because I was like, I thought you’re just supposed to get it out of me now, like just surgery first, that’s what I understood. But again, I did trust the doctors and they said, “Well, actually, if we can shrink this a lot, then that’s the best thing.” And you really do get an education.

So I did that chemo first. My tumor shrunk about 75%, then I had a lumpectomy, I had surgery about 5 weeks into COVID, and that actually influenced my treatment decisions based on what the hospital would do at the time. And then, based on the pathology after surgery, I was given a recommendation that I decided to go with for adjuvant chemo. So I did 14 months, or 14 rounds, post-surgery and post-radiation.

I finished active treatment March 2021 and began endocrine therapy, which is another whole aspect of care for hormone-positive cancer. So that’s a little bit about, and

Amelia O’Relly [00:07:45]

Thank you for that. So many questions that immediately pop to my mind just going through that. I can tell you my own experience as well, 2019. A lot of what you shared is very similar to what I was experiencing as myself. At the time I was metastatic, so I was already off and running as they say. But what’s interesting is you mentioned, you had a really good footing, a toe up into what is standard of care. I would say that I was probably on the other end of that because there was no history in my family, and I had always had clean mammograms. I had no idea that this was even possible, and it was already metastatic when it happened.

I’m curious, Dr. Dizon, for patients who do not begin with a baseline of what standard of care is. I’m curious, what are some things that you recommend people try to understand at the point of diagnosis so that that informs their treatment decisions. Because I wish there was so much more that I would’ve known back then. And I had excellent care, and I still do, thank god, but what are, what would you say they need to understand at the beginning of that diagnosis?

Don Dizon, MD, FACP, FASCO [00:08:56]

I don’t think there’s anything that they need to understand at the diagnosis, is what I’m going to say. What Blakeley taught me is that people learn over time. What Blakeley did, because she needed to understand—and this is not uncommon, I think many people listening have the same experience—she needed me to repeat things, and then she needed to ask why. Why am I going to do this part? And she wasn’t shy about it. And I think the difference between someone who doesn’t know anything about medicine and is coming to this completely cold. Like they were never going to go to the doctor until they were 90 with a heart condition. And all of a sudden they’re young and they’re coming to a doctor with cancer. Blakeley, probably you did have that experience in medical health and medical communication. Plus there were other things. I don’t know if you want to get into that.

Blakeley Schmidt Anderson [00:09:49]

I should clarify that I knew absolutely nothing about breast cancer standard of care, nor did I know anything about standard of care for my specific diagnosis. I understood what the concept of standard of care was. Quite honestly, it was actually from diabetes education. I had just heard this word like this phrase before, standard of care. And this is kind of like, this is the baseline of what should be happening at hospitals across the country.

But, again, throughout this whole process, I live in New England. I’m very close to some of the major academic teaching hospitals from Brown which is right down the street from Harvard, which is close to Mass General. And then we’re close to Yale, New Haven. We really have a lot of education and science going on in this area. And for that, it really changes.

And the other piece that Dr. Dizon is referring to, probably, is that my diagnosis at 36 came about 4 years after my mother’s death from ovarian cancer. So I had been a caregiver for her for 3 years during her treatment, and I understood that very well. However, I immediately then thought that I had the same fate as my mom who had died 4 years prior. For which he assured me that at that point in time it was not the case, and it was a very different diagnosis. And so I had a lot of challenges coming in just to be like, “OK, you’re not going to die. You’re going to be OK.” That took a while to wrap my head around. Like, “OK, this is a different disease.”

And then in breast cancer land, as we’ve already said, there’s so many different varieties. And then even varieties within the varieties.

Don Dizon, MD, FACP, FASCO [00:11:54]

I don’t know if you sensed it, Blakeley, but I remember when we were going through your receptors we were like, it is a hormone receptor-positive, weakly so, but it was almost like, but it’s also HER2-positive. And I think I was a bit excited about that because we had treatments for HER2-positive disease. That work really, really well.

I’ve learned from treating folks like Blakeley that there is no optimistic news when it comes to cancer, that having HER2-positive disease is not something to celebrate for someone who’s just newly diagnosed. It’s good to know that there are treatments for that.

But to get to your first question, Amelia, it’s a process. And what Blakeley did was advocate for herself, and she needed to understand why. She did her own reading and I fully supported her having a second opinion as well. But she wasn’t satisfied with the first go-round. And she also wasn’t shy about asking me for clarification. And I think, throughout it all, it was a process of actually, it became like almost two colleagues discussing the data.

Amelia O’Relly [00:13:09]

And that’s so important. I had to quickly ramp up myself as well because I came from a background of being in corporate America where we were doing high problem solving all the time. You walk into this problem that is life and death, and you’re trying to, all of a sudden, amass all that information. And many times you feel ill-equipped. Looking back now, I think, “Oh, these are some of the things that I would’ve wanted to ask right at the beginning,” or at least to have that readily available that I could address.

Something that you both said, so I’d like, Dr. Dizon, for you to kind of start off and then Blakeley to provide some perspective is how do you communicate, then, with a patient that doesn’t necessarily have that strong decision making or advocacy for themselves. Not everyone is in that same, it’s a continuum, and some patients have less comfort with that. There are many cultural factors that play in, or even just where they are or how they’re processing all this information at once.

So what are some things and how do you communicate with the patient that is not as driving as, I’d say, we were at the beginning of this?

Don Dizon, MD, FACP, FASCO [00:14:28]

I think it’s first to understand that people are very different in how they make decisions. And that’s OK. I’ve run into a fair share of people who say “I trust you. I’ll do whatever you say.” And they really don’t want to get into the details of it. They just want to know what the plan is. My job is not to force them to understand my rationale for it, but it’s to say, based on everything, this is what I think, and this is why, how do you feel about it? If they say, that’s fine, let’s just do it.

I will do one thing — and everybody, if they’re like, “whatever you say” to folks like Blakeley who is like, “I just need you to map this out for me. I want to digest it, and then I want to talk again” — everybody I meet with gets the same conversation twice. I will tell them everything that I know about their cancer, I’ll get to know them. I’ll propose a plan, I’ll go through the plan, and then I’ll say, “I’m going to give you information, you’re going to take it home, and you’re going to show it to people. And then you’re going to come back in a week and we’re going to have this conversation again. And we’re going to start with your questions.”

Amelia O’Relly [00:15:46]

I love that. I love this notion of twice. Because you have to download some of this in your own mind to at least sit with it for a minute.

The challenge sometimes though is the speed at which everything is moving. But I love this point that you’re making around, let’s go through this twice, because so often you feel like you have to do it in the moment.

Don Dizon, MD, FACP, FASCO [00:16:13]

Yeah. And I think it’s really important that people know that if you need that extra week to synthesize it, so it makes sense for you, that’s not going to be the determining factor of whether you live or die of cancer.

If it feels like a moving train, ask me if it’s OK to stop the breaks. Because oftentimes there is time to be thoughtful. And I can say, treating folks like Blakeley, who are really good advocates for themselves, reinforces this idea that people oftentimes need information, and then they need to get out of the cancer center and then come back.

Amelia O’Relly [00:16:55]

And that brings me to another point. Is the role of the provider, or the healthcare provider, leading versus guiding, or a blend of the two? What would you say is primary? Should they be leading? Should they be guiding? How should they be coming at it?

Blakeley Schmidt Anderson [00:17:18]

I like advising because ultimately everybody is in charge of themselves, and everybody should be the boss of themselves and what happens to them. I am someone who is naturally very outgoing, so that helps. I try to make a lot of this a little game, because why not. It makes it more fun when it’s actually miserable. I’d be like, “OK, let’s go try to stump Dr. Dizon. I’m going to throw him this wild card and make him work today.” Like, he doesn’t get to phone it in ever.

Don Dizon, MD, FACP, FASCO [00:18:00]

No, I don’t think you can ever say that I phoned it in with you.

Blakeley Schmidt Anderson [00:00:52]

No! No, no.

The other piece is that I was someone who’s like, “I want a plan, I want a roadmap,” but at diagnosis day, I wanted a roadmap for the next, what was almost 20 months of treatment. And depending where you are, kind of re-gauging your thinking and taking one step at a time. This has been a lot of work and I’ve done a lot of yoga work and a lot of different complementary things to help — a lot of therapy, a LOT of therapy — to think about, well, we don’t even get to make that decision yet.

The first step for me was neoadjuvant chemo. And then you have to recognize that nobody can know necessarily what type of surgery until you see how effective that chemo was. And then you have surgery and you get pathology results, and then that information informs the next step. Even from the outset, Dr. Dizon couldn’t tell me how long is this going to take. Because he didn’t know.

Of course when I got my pathology results after surgery and I found out I was going to have, I think it was 9 more months of treatment instead of what I had thought was going to be 6 more months. Even though that 3 more months, you showed me in hindsight, at that moment, it just sent me absolutely reeling. Because I was like 9 more months, and for me, 9 months was a trigger because I had wanted to have a baby before cancer. I was like, oh my gosh. But definitely really trying to come up with this mentality that you are in charge of yourself and this is your life. It’s a very silly comparison, but like if you’re at the hairdresser and you’re too afraid to be like, “No, I don’t like that cut.” You have to really, and that’s of course, that’s a hard topic in cancer land, as I like to call it, with hair. But you have to really speak up because this is important. And nobody cares about you as much as you should care about you.

So yeah, that idea of kind of decision points and really trusting yourself. When I was deciding where to get treatment, whether in Boston or Providence, I asked myself a lot of questions that didn’t really have anything to do with care. How long am I going to have to be in the car? How many days a week am I going to have to go? Who’s going to be able to take me? There was a lot of things that I asked myself to see how well it sat with me. And that also what informed my decision. It wasn’t just like a doctor or just the treatment.

Amelia O’Relly [00:20:55]

And I think something that you said is also a really important point. At the beginning when you were talking about the plan. I’m very similar. I wanted a plan. I think what I would say is, for me, my treatments failed for the first 18 months. And it was not because of any gap in care. My care was also a prestigious organization, Cleveland Clinic. I mean just top-notch. And the challenge was, it was just not responding. It kept failing. I went through seven lines of treatment in 18 months before we found the one that worked. And in the process of that, it was getting ridiculously worse.

The point that you made around the plan and not setting yourself up for that expectation is because there are nuances that happen. There are failures that could occur. Dr. Dizon, you talked about recurrence or a change that could happen. Now suddenly now the treatment has to go a different direction. So I think that it’s also very important to give yourself, as a patient, that grace that things are going to ebb and flow. And that is super, super hard to digest.

You both touched on additional pieces like the role of therapy, which I did as well, as well as yoga and other things. Can you touch a little bit also on this notion of how the patient can prepare themselves for what could be failures? Because that could happen, sometimes very quickly, sometimes it’s OK for a little while and then a spring pops.

So, Dr. Dizon, I’m curious, first from you, around the navigation of that, especially the first 6 months of treatment. That can be so very tricky.

Don Dizon, MD, FACP, FASCO [00:22:38]

Some of the conversations that, Blakeley, we had were only peripherally related to the cancer and its treatments. It was really about how am I supposed to be living through this? It’s at some point, and Blakeley’s not alone in this, but it was terrifying. The first 5, 6 months was terrifying. I would see women every time they came in, they were in tears because they worried I was about to say something. Like, it’s not working.

There is this fear of progression. There is this fear of recurrence. And it’s a very, very real phenomenon. And again, I think this is what we learn from the people we treat. And Blakeley has been one of my best teachers. We need to understand that people don’t leave their cancers in the cancer center. It follows them. It follows them home. It follows them while they’re trying to reincorporate their lives. And if someone is struggling, we need to give voice to that.

There is always a chance that things aren’t going to go the way as planned. That this map, that, Blakeley, you’re carrying around with you, there will have to be a stopping point. And then maybe even a U-turn, or we’ll have to go right when we thought we were going straight. And the journey may get more circuitous, but at least acknowledging that that’s true. You’re not providing this false sense of security that it will all go fine and this is a blip, but you’re still on the right path. Then 3 months later you’re dealing with someone whose treatment failed, and are like, “Well, let’s just go on the next one.”

Not only that, some of the things that we spoke about was just how hard the treatments were. And it was such a thing that we spoke about. It’s like, how do I navigate this? Do I have options beyond this horrific thing you have me on? And really, I challenge you, Blakeley a lot about we could stop this,

Blakeley Schmidt Anderson [00:24:52]

And that actually has come up, the idea I think about stopping it. I’ve been on endocrine therapy, and that is an actual nightmare. For anyone who might be starting it or going through it, some people do really well. I actually did take a break from it. I’m currently on a break from endocrine therapy. I didn’t realize how terrible it was until I went on a break because I had compared it to active treatment, active chemo, and comparatively endocrine therapy is a lot easier, quote unquote, than active chemo where I had lost all my hair, I was nauseous constantly. Not being nauseous constantly and having my hair grow back, those were two huge pluses. However, there’s a certain level of misery that is constant.

This idea of choices, and I have spent a lot of time thinking about what’s in my control versus not in my control and what can I choose? And I’m talking everything from alcohol to whether or not it’s fine to eat cheese because I was hormone receptor-positive. And depending on what you want to read and believe that that’s something in my choice. It’s like I have control over whether or not I drink alcohol and whether or not I eat cheese, which seems silly, but I know it’s a thing. I just had to kind of really think about what’s going to be best for me.

Then there’s this something that we talk about: What is your appetite for risk? Because with this idea of endocrine therapy especially, I could say no. Like I could say I absolutely don’t want to do it. I feel so much better off of it. However, I do very much view all of my doctors as extremely highly educated consultants. And they’re like, “Based on what we know, this is what we recommend.” And then Dr. Dizon was extremely good at being like, “And it’s your choice.”

Really wrapping your head around that and putting yourself in this mentality, “I am in charge of what happens and I can choose to not do it.” There was a point after I had started endocrine therapy where I needed to make a change. I actually went to the doctors in Boston. I got their opinion, and they said — for reference, I did Lupron injections monthly, and then I started with the L one

Don Dizon, MD, FACP, FASCO [00:27:48]

Letrozole.

Blakeley Schmidt Anderson [00:27:49]

Thank you. Letrozole. I was going to say some other L, I can’t. Yeah, letrozole.

And it was terrible. And Boston had said, “Well we would just put you straight on tamoxifen.” And Dr. Dizon was like, well, you could go straight on tamoxifen or you could try a different AI. So I quite literally took the side effects of tamoxifen and Arimidex, which is what I wound up taking. I read the side effects, and I saw that, and I compared the side effects. And I was like, I’d like to try Arimidex before I go to tamoxifen. So that’s what I did. And that was where I felt comfortable and that was the kind of decision I made.

Amelia O’Relly [00:28:35]

And it is an important point that you’re driving here, because I did the same with my own treatment. It’s this notion of balancing risk and how risk balancing allows you to make choices. Because I think what happens all too often — and I’ve lived this experience, I’ve also known, like you, many other folks in it as well — is there is a standard protocol, practice associated with whichever medication treatment path you are best prescribed to take. But the side of that is all the other adverse pieces that come with it.

And it isn’t as though that prescribed path is a 100% guarantee to the point that you made earlier, Dr. Dizon, there’s no guarantee on one end, there’s no guarantee on the other end. So you have to live in this navigation mode. But the ability to balance the risk with making choices is an important piece that I think that I’m so happy to hear you convey to this audience group. I’ve done the same, we’ve made, my doctors and I, adjustments to my treatment cadence to manage those side effect components because quality of life is an important piece. And also the adverse effects, what I call compounded interest the wrong way. There is so much that is happening to the body as well. You’re trying to balance those two pieces. And I think it comes down to weighing the risks of here’s what it means and here’s how I’m living my life day-to-day versus these other pieces that I can do to try to stretch it a little bit more, right.

Don Dizon, MD, FACP, FASCO [00:30:17]

But I think the more important thing is that the person who needs to make those determinations about risk and side effects and benefits and all that. It’s not me.

Amelia O’Relly [00:30:28]

It’s the patient.

Don Dizon, MD, FACP, FASCO [00:30:30]

Blakeley took, she did, she read on everything and said, "I would prefer to do this." And I was like, "OK, that’s what we’ll do."

Amelia O’Relly [00:30:43]

And the piece that I think that some folks are also bringing up in the Q&A is that there are some patients whose doctors who are not as open as you are, Dr. Dizon, to the role of the patient as also a co-navigator. Or they don’t have the access or are not as connected to the latest things that may be available. How does a patient navigate that piece?

I’m a fan of second opinions. I got them as well at the beginning, and I’ve gotten them even at junctures during my treatment when we were thinking of making adjustments. But that was also encouraged by my doctor. They wanted another set of eyes. They welcome that. But some of the comments that we’re getting is what if I’m with a doctor that isn’t able to answer my questions, that doesn’t necessarily know those things. What path can I take, or should I take, as a patient?

Don Dizon, MD, FACP, FASCO [00:31:43]

I think a conversation I have with pretty much everybody is that I work for you. I work for the people that I’m treating. It’s not the other way around. I’m oftentimes really trying to assuage concerns when people leave my practice, or when people go for a second opinion, decide to stay at a different institution, you are well within the rights to get the care that you need with the person who you best identify with.

I think it is harder in a more rural community or in a smaller city, where there’s really one medical practice and they all belong to the same practice. And then there are the intricacies of “I don’t want to piss off Doctor X, so I can’t take you on.” I think feeling stuck like that is a very big dilemma. And I think what Blakeley can teach everybody is, even in scenarios where you don’t have the choice of a provider, you can still expect them to do more for you.

And I think that’s really what Blakeley, our communication style has gotten to the point where I anticipate that not only is she going to want to know what did I learn from the last meeting I went to, and this decision to go on a break was certainly, I mean, we were communicating via Instagram with each other as this data came out. But I know that she’s following the literature as well as I. And I can expect those conversations when we meet. And I think at some point, my hope is that people and their relationship with their doctors does morph into something beyond doctor-patient, where relationships develop. And I think that’s the best of both worlds.

But for anyone who’s stuck and embarrassed that they can’t upset their doc or stuck with a doc who is not listening to them, it’s OK to say to yourself “I actually deserve better than this.”

Blakeley Schmidt Anderson [00:33:59]

And there are, I don’t know very recently, but I know that a lot of the major cancer institutes do offer virtual second opinions. So if you are somewhere where you don’t have access to a major cancer center, and this isn’t something that I’ve looked at recently, but Dana-Farber is where I went. Because also Mass General is in Boston, but Dana-Farber is where my mother had gotten treatment, so that’s also where I went for the second opinion. And I know at that point in time, they did offer virtual second opinions. So even if you’re somewhere else in the country and you would like them to review your case, then that’s something to look into.

I’ll also say that, at the very beginning of my diagnosis, I got three different options for treatment, for neoadjuvant chemo. Dana-Farber said these are the two different things that we could do. And then, I call it Dizon’s Delight. At home, I’m like, “He’s mixing up my chemo cocktail.” And it was slightly different. It wasn’t exactly the same. It was based on a different study. But I collected enough information at that point in time, and now we’re talking within a couple weeks of diagnosis. We’re talking, I found a lump the first week in October. This was the first week in November. So this was very early on. Because at some point, I do like to think about what’s in my control and what can I do, and this is my decision.

There are definitely points where I’m just like, the heck with it, I’m just going with what they say. Because it’s too much. I don’t have the energy fight or care. I mean, I cared. I was like, I don’t have the energy to read another thing. And I didn’t Google a lot. I looked at very little bits. I would reference the studies that Dr. Dizon or other doctors were talking about. And I’d be like, yeah, sounds good. And that was good enough for me.

Sorry, I’ll just add that I keep referencing this break. So it’s important to add that the break, the literature, the study that I’m doing this break based on is the POSITIVE study. It’s a maybe baby break for me right now. I decided to take a break because prior to treatment I had wanted to have a baby. And that was, I think I actually mentioned it in my bio, because before I did any of this, I actually did fertility preservation. So this study that I’m throwing my life, I’m resting my life on right now is the POSITIVE study. That’s what it’s called.

Don Dizon, MD, FACP, FASCO [00:37:08]

Yeah, it was a huge breakthrough for us at the breast cancer community. Because it actually put figures down for women with hormone-positive breast cancer who decide to stop endocrine therapy so they can try to get pregnant. And it wasn’t a randomized trial or anything, so we don’t have a figure, but the risks were not that high. And again, Blakeley and I reviewed it and we made decisions, and she made decisions about this falls into the risk that I’m comfortable with to achieve this goal that I’ve always wanted for myself.

Blakeley Schmidt Anderson [00:37:49]

I just don’t think about it that much. It’s like I make a decision. I’m like, that’s the decision you made.

Don Dizon, MD, FACP, FASCO [00:37:53]

It took you a while to get there, but you did make that decision

Blakeley Schmidt Anderson [00:37:56]

Well, it did, and that, I mean, it’s been almost 5 years.

I can say that the amount of practice I have had to do, just like, “This is the decision you made. You can make a different choice.” But this idea of the plan, like I really wanted an absolute roadmap at the beginning, and I had to recognize that it’s not realistic because you never know.

Amelia O’Relly [00:38:23]

And you have to be able to let go. I think that was really, really difficult for me because, similar personality, very much of, “OK, we’ve got to have a plan, we’ve got to understand these pieces.” There are a couple of points that I want to underscore for those, because I think the points that you’ve made have been so incredible.

One is this notion of virtual second opinions. I don’t want to lose that because that’s something I also did and it was immensely, immensely helpful because it’s a way to have access and to reach — we did with Dana-Farber, with MD Anderson. So you have a chance then to get to other doctors that you may not have available in your own little zip code of the world.

The other piece that I think is important also is this notion of risk assessments. And we’ve had some questions on, is there some risk assessment information out there that, or protocols out there that I can use navigating through this.

Sometimes I think it’s what you said, Blakeley, it’s like, let’s just go. I’m letting go and I’m going to see what happens. But I think there’s also to the extent that there are some questions that help patients understand how to assess risk.

For me it was intuitive. I started to think through side effect management, how we are doing with the scanning. So I started to layer in the data that I was collecting for myself, and I used that as my risk assessment protocol. But are there some other things that, Dr. Dizon, either you know of or things that you tried that helped inform your risk assessment? I think it’s an excellent question on the Q&A chat that just came through.

Don Dizon, MD, FACP, FASCO [00:39:55]

Yeah, I think because breast cancer is so different now that I think it’s hard to generalize about risks and benefits that’s going to work for everyone’s kind of breast cancer. I think, practically speaking, it’s not only important that I tell you my impressions of a drug, but that I actually hand you information, really hard information that says, this is what this drug is, and this is the reported side effect profile.

So I told you stuff, here’s some things to look at as well, this is option B, I can tell you this and here’s some information on that. And if there’s an option C, give you that stuff as well as information. And then give you time to process that and then come back.

Again, it’s what Blakeley taught me is that people will actually look at that. This is not something that’s like, OK, my doctor gave me stuff and I’m just going to put it in a drawer and never look at it. If your life is depending on it, you’re going to look at it, and you’re going to see things that say, I am not able to accept the risk of uterine cancer with this drug. I’m just not. Believe me, I was like, “It doesn’t happen to young women. It’s a really rare side effect and these are the risk factors.” But at the same time, you’re the one that had to take the drug.

Blakeley Schmidt Anderson [00:41:24]

And that was the deciding factor for me on the decision of tamoxifen versus trying a different AI. For me, reading that uterine cancer could potentially be a side effect of tamoxifen. I’m like, “Nope, not doing it.” I’m going to deal with the AI and just, that was my choice.

Tamoxifen, I might do much better on tamoxifen. The side effects of endocrine therapy that I experienced were fairly extreme to the point it impacted my relationships, with my husband. Like every, I think Dr. Dizon a sexual health clinic written about that’s on his bio. That another part of it, every aspect of my life.

There’s a lot of acceptance that has to go into it. I hated the idea of taking antianxiety medication to counteract the endocrine therapy. I hated it. I’m like, I hate this. I hate it.

And I’m going to do it anyway.

Because I found out that that worked really well for me, and I felt a ton better. It didn’t make everything go away, but it made things more bearable.

Amelia O’Relly [00:42:48]

What would you say the role of priority setting within your life kind of played into some of those decisions? Because I feel like depending on where someone is in their life, right? And I think sometimes we don’t think about that intuitively. Like you clearly did, you had priorities that you put into your decision. How did you, how did you kind of make that happen?

Blakeley Schmidt Anderson [00:43:17]

One thing that I have thought about a lot is that I really worked a lot on acceptance. And I kind of sunk into it. I didn’t fight against the fact that I had cancer. And a lot of that actually is because my mother, when she was going through treatment, she really had this like, battle mentality. And she’s like, “I’m going to beat it.”

My mom, had a massive debulking, a 12-hour debulking surgery for basically stage four ovarian cancer. And she decided to walk a three-mile walk for Dana-Farber, fundraising for Dana-Farber, 3 weeks after she had the surgery because she was so damn determined. But my experience was, I was like, well, that didn’t necessarily turn out for her very well. So my approach to treatment was to just like, accept it.

And if anything, I probably didn’t mush into the couch as much as I should have. I was in a position where I could take a leave of absence from work, and I did, I took a few months off during the worst of treatment. And I just had time to just like be with it and sit a lot of hours by myself sitting on the couch, and really kind of thinking about what’s important to me and that was what I wanted to do. And that felt right for me. Just accepting this is where you are and you’re going to go through it and you’re going to feel your way through it, like based on your gut.

But that was a lot of work. This is, I’m almost 5 years out from diagnosis. I had four different therapists that I talked to regularly during active treatment. I talked to the chaplain at the hospital, like practically every time I was there. I had a couple therapists that I talked to sometimes. I had my own personal therapist. I tried different things. I spent a lot of time just navigating this because it is an absolute nightmare. I mean, it’s a nightmare.

We can make it as light as we want to, but it is an absolute nightmare, and it sucks. Yeah. Absolutely sucks. The toxic positivity bullshit, I’m like [laughter].

Amelia O’Relly [00:45:51]

I am right there with you. I am right there with you. And I think that the word that you said that’s so critical is acceptance. I think that acceptance does not mean defeat. And acceptance is not a weakness. Acceptance is the ability to actually come to grip with what the reality is in that moment, knowing that the reality is going to change. And sometimes that reality can become bad for a little bit or for a long bit, or it can become really good for a while. But I think if you’re constantly bracing for impact, your body’s going to take a lot more of a hit. And because you’re constantly in this brace impact as opposed to, “I have to, kind of, accept it and then navigate through it.” I think I took a very similar approach early on.

Blakeley Schmidt Anderson [00:46:35]

Sorry to interrupt. There’s a book called Radical Acceptance. I haven’t read it. I like to read like the highlights. I want to read an intro. I might come across like I’ve read every single study. I read the abstract, so I read like three paragraphs. That’s enough for me. And then I make my decision. The book Radical Acceptance. I’ve never actually read it. The title was enough. I just have gone to that. Like I’m like, “OK, this is happening, and so what are we going to do about it?”

And it sucks. I did a brief foray into improv comedy in the past couple of years. And they say, “Yes, and.” So there’s no wrong answer. It’s not a but situation. It’s, yes, I have cancer, and what are we going to do about this? And how are we going to move forward? And what can I do to make the best of it?

Amelia O’Relly [00:47:40]

I love it because it is exactly that. It’s a point in time and that’s all we can get to, one at a time. As they say.

We’re getting to the end of our hour here. This is such a rich discussion. We could go on, I know, for forever. I know I could.

I’d love any final thoughts. Any other comments or things that we didn’t get to touch on that you really want to convey to the audience? I know we only have a few minutes left, but I’d like to at least give you a chance. Any other thoughts or comments?

Don Dizon, MD, FACP, FASCO [00:48:13]

I would just say that I think remembering that this is your life we’re talking about. Going in with that strength, and not even worrying about if your question is stupid or simple or not appropriate. If you have a question, you have to ask it. And if you are afraid of something and, Blakeley, you did this so well for me, if you’re afraid of something, say it.

At some point it was like, “Oh, I have this pain, blah, blah, blah, blah.” And I was like, OK, we’ll watch it. Blakeley would be like, “I don’t feel right, and I’m worried about a recurrence.” And it totally took a totally took the conversation a different way. We can’t read your minds as your docs, but we can certainly help put you at ease, in case it’s something serious that you were worried about.

That kind of honesty, I think it does take some strength, but at the end of the day, we work for you. So you need to tell us what we need to do to help.

Amelia O’Relly [00:49:16]

I love that you say that. It changes the patient role to the customer. The patient as the customer as opposed to the patient as some other individual.

Blakeley, any other closing thoughts before we wrap up?

Blakeley Schmidt Anderson [00:49:33]

Yes, I would just say really do advocate for yourself because it is your life and you have one life. It is easy for me to say because I’m a very loud, outgoing person to begin with. However, whatever any individual person can do to search deep down inside to be like, just take charge. You are the boss of what happens, and just own that. And trust yourself. If you have a concern, bring it up because there’s a lot to be said for gut instinct.

Amelia O’Relly [00:50:17]

Absolutely. Very well said. And I can’t thank you enough, both personally, as a patient in this journey, as well as the moderator for today. And on behalf of LBBC, and just thank you so much for this phenomenal conversation and for your candor and your openness.

Session 2 | Innovations in treatment and side effect management

Jean Sachs, MSS, MLSP [00:00:10]

I am so thrilled to introduce you to today’s speaker, Dr. Eleonora Teplinsky. She is a medical oncologist who specializes in breast and gynecologic cancers. She is the head of breast and gynecological medical oncology at Valley-Mount Sinai Comprehensive Cancer Center in New Jersey.

Many of you may be familiar with her because she’s very active on Instagram, @DrTeplinsky. So if you don’t follow her, I encourage you to do so. She shares all the time and is so compassionate and educated, it’s a great way to stay up to date. She also has a podcast called INTERLUDE: Cancer.

I am going to turn it over to Dr. Teplinsky, and I will come back from time to time to ask some of your questions. Just remember put your questions into the chat.

Eleonora Teplinsky, MD [00:01:04]

Hi, everyone. Thank you so much, Jean and the rest of the team, for having me. The goal of today’s talk is, it’s a big topic. We’re going to talk about some of the newer treatments for both early stage and metastatic. We’re going to talk about triple-negative, HER2 positive, hormone receptor positive. And it’s really a high level overview of what’s happened in the last few years, what’s happening, what we can see in the future, and how to manage some of the side effects. It’s a lot to do in an hour. Please feel free to put any questions in and we’ll try to answer as many as we can.

These are my disclosures. None of them are relevant to today’s talk.

The overview that we’re going to touch on is that the landscape of breast cancer treatment has changed drastically over the last few years. There’s changes in treatment paradigms, both in early-stage and metastatic breast cancer. When thinking about how it would be best to structure this talk, I thought we’d break it down into really four classes of medications that have revolutionized how we are treating cancer. We’re going to talk about antibody-drug conjugates, immunotherapy, CDK 4/6 inhibitors, and some of the novel endocrine therapies, some have been approved and some that are being studied. We’ll talk about the mechanisms, the drugs, what they’re approved for, and touch on side effects as well.

Let’s start with antibody-drug conjugates. There are a lot of medications that fall into this class, and we’ll talk about what they are, but this is Enhertu and Kadcyla and Trodelvy among others. Essentially what they are — it’s different than chemotherapy, it’s different than what we traditionally think of as immunotherapy like Keytruda — these are classes of medications that have three components, and you can see that here in the photo. The three components are, there is an antibody, then there’s a drug also known as the cytotoxic payload, and then the two are linked together via a linker.

The antibody will bind to a specific protein or receptor that is going to live on certain cells, including our cancer cells. And when that antibody binds to the cell, the linker then activates to cleave the antibody from the drug, or from that cytotoxic, or cell death, payload. And then the drug enters the cell and it can cause cell death. It’s binding to an antibody, but then really injecting something really toxic into that cell. And the benefit of antibody-drug conjugates is it spares a lot of the normal cells so that it’s a very targeted cell death. It’s more effective. It has, in general, a little bit less toxicity because it’s not targeting all of our cells. Some people call it the biological missile for targeted cancer therapy. And I like that because it really speaks to how it’s very, very focused.

A lot of our antibody-drug conjugates have what’s called a bystander effect. The idea is that the toxin goes into that cancer cell but it kind of spills out in the tissue surrounding that cancer cell in that targeted region. You’re kind of bathing the cells around it. So it’s a little bit more effective but it can also cause more toxicity. A really simple way that I like to think about it is if you’re making jelly donuts and you inject the jelly into the cell but some of it spills out and kind of gets on the surrounding area, that’s kind of what an antibody-drug conjugate will do. It’ll get inside that cell for that very targeted delivery. But then kind of go on a little bit outside as well.

Eleonora Teplinsky, MD [00:04:55]

Enhertu is the big antibody-drug conjugate that a lot of people have heard of, and it’s used for really the majority of metastatic breast cancer at this point. Enhertu was also known as trastuzumab deruxtecan. It’s also known as T-DXd. So the T is the trastuzumab, we know trastuzumab as Herceptin. Trastuzumab is an antibody that will bind to the HER2 protein, and then deruxtecan is the drug that goes inside the cell. The drug binds via the trastuzumab, the linker is cleaved, and then the deruxtecan is released inside the cell.

You can see here, after it causes cell death, you’ve got that bystander effect where it goes into that neighboring tumor cell.

Enhertu was first approved for HER2-positive disease. And then because of that bystander effect they realized that you don’t have to have a lot of HER2. Even if you’re HER2-low and have a little bit of HER2 expression, because it goes to the neighboring cells it’s very effective. So it was approved now for HER2-positive and HER2-low metastatic breast cancer. There’s also data for ultra-low where you have just the tiniest amount of HER2 expression, but it’s not FDA approved for this indication yet, although people are using it.

In terms of what HER2-low is, prior to this distinction, people would say you’re either HER2-negative or you’re HER2-positive. And in early-stage breast cancer, because we’re not using this medication yet in early-stage — stage I through III — we’re still really kind of binary, negative or positive. But in metastatic disease what happened with this study was there became this new classification. The photos up here are what a pathologist looks at to determine if something is positive or negative based on the amount of HER2 expression. And if you have no HER2 expression at all, you’re negative. Although we’re now starting to group some of these into an ultra-low category. And then if you are 3+, you can see it’s a lot of HER2 so you’re positive. If you’re 2+ it’s equivocal. There is a confirmatory test that we do. And if that’s negative or 1+, meaning just a little bit of expression, then you’re HER2-low. And when we were able to give Enhertu to this population, we were able to treat a significantly greater number of patients with metastatic disease, which was really amazing.

This study was the DESTINY study presented at ASCO back in 2022, I believe it was the DESTINYBreast-04 trial. They looked at patients that were HER2-low, and they found that it essentially doubled the time that people were on the medication without experiencing disease progression or dying from breast cancer. And this very quickly became the standard of care in that HER2-low. It’s really offered up a number of new treatment options for many, many patients that didn’t have it before.

The other antibody-drug conjugates in breast cancer are Kadcyla and Trodelvy.

Kadcyla we use for either HER2-positive metastatic breast cancer as well as for patients who have early-stage HER2-positive disease who had neoadjuvant therapy, did not have a pathologic complete response. And so rather than continuing Herceptin and Perjeta, we will switch to Kadcyla for a different way to target HER2. We have Trodelvy, which is used for metastatic disease, both in triple-negative and hormone receptor-positive, HER2-negative.

All of these have a different target. For example, Trodelvy doesn’t bind to HER2 like Kadcyla or Enhertu do, but it binds to the TROP2 protein, which many cancer cells express, and then it delivers SN-38, which is a topoisomerase inhibitor. It’s a different type of drug. These drugs are extremely effective and have really changed how we treat both metastatic and early-stage breast cancer, in terms of Kadcyla.

Datopotamab deruxtecan is a novel antibody-drug conjugate that is very far advanced in clinical trials and not FDA approved yet, but we’re going to wait to see if that happens. There are over a hundred different antibody-drug conjugates in development — not just for breast cancer, for many different types of cancers. This is a field that’s really growing quickly. In breast cancer right now the majority of the data is in metastatic disease. But we’re starting to move some of these drugs into the early-stage setting, and I’ll show you that a little bit later on.

In terms of side effects, the side effects of antibody-drug conjugates are related to that payload. That’s the drug. Remember: the antibody binds, the linker is cleaved, and then the drug gets injected into that cell. The side effects are related to that drug. And they vary, they can include low blood counts, neuropathy, hair loss, fatigue, diarrhea, GI toxicities. We see liver enzyme abnormalities. The big one for trastuzumab deruxtecan that we watch very closely is pneumonitis or inflammation of the lungs. There is about a 12% incidence of pneumonitis happening and we have to follow it closely and stop the treatment and give steroids if we see it because there are very serious consequences of pneumonitis.

Different antibody-drug conjugates will have different side effect profiles, and improving tolerability and toxicity is important because we get more benefit from that bystander effect but we also have more toxicity. It’s a trade-off.

Before we move on to the next category, Jean, are there any questions that are coming on ADCs that we can answer?

Jean Sachs, MSS, MLSP [00:11:39]

First of all, thank you. That slide was so helpful and I’m seeing in the chat that a lot of people really appreciated it.

One question is: What about dosing? Does everyone start at the highest dose with Enhertu? How does that work if the side effects are really hard?

Eleonora Teplinsky, MD [00:11:49]

I think that’s a question that people are looking into and trying to figure out. Does everyone need to start at the highest dose? For now, it’s on an individual basis, seeing how people are feeling even going onto that drug. I will have some people that I start at the highest dose and other people who are already coming in and maybe they’ve been on a prior treatment where their blood counts are low or they already have some underlying GI toxicity. I may start them at a medium dose. So there’s not really a one size fits all.

I think it’s having that discussion with your doctor about can we talk about the dose that we’re starting at. Are we starting at the highest dose? If so, I’m concerned about , these side effects, how are we going to manage it? But for now the standard starting dose is 5.4 milligrams per kilogram, it’s based on your weight. But some people may start at a lower dose and that really is that individual discussion. And the same thing goes for our other antibody-drug conjugates.

Jean Sachs, MSS, MLSP [00:12:57]

That’s helpful. So for everybody listening, this is important, talk to your doctor about the dosing.

It’s also important, now that we know about HER2-low and ultra-low, that your biomarkers get retested. If you want to talk a little bit about that.

Eleonora Teplinsky, MD [00:01:04]

Yeah. Ultra-low, we’ll take that out of it just for one second.

For HER2-low, you actually don’t need to get retested because it’s already going to be on your pathology report. The pathology reports, both for early-stage and metastatic are going to describe that HER2. So they’re going to say is it 1+, is it 2+? And then, based on that your doctor said you’re positive or negative. Now you can, just by looking at your pathology report, and going to that slide I showed you with the 0, 1+, 2+, 3+, you can actually say, oh I’m HER2-low.

Now ultra-low does need to be relooked at because these are ones that are being scored as zero because there’s really very little expression. This does require the pathologist to take a look. I have called the pathologist and said, is there any HER2 expression? I know you said it was zero, but was there any signal at all? And so that does need to be relooked at.

Jean Sachs, MSS, MLSP [00:14:15]

Great.

I’m going to ask two more questions together and then you can move on. One is: Will Enhertu be available in early-stage? Do that one, and I’ll find the second one.

Eleonora Teplinsky, MD [00:14:27]

Great question. Every drug always starts in the metastatic setting for a number of reasons. It gives you efficacy a little bit faster because people have active disease and we can see, did it respond or not. There are clinical trials of moving Enhertu into the early-stage setting, they are ongoing. A lot of that depends on how quickly that those studies accrue and what the results of them are, so we’ll see.

Sometimes things that work in the metastatic setting don’t work in the early-stage setting. We’ll see that a little bit later on, but I don’t have any information one way or another at this point.

Jean Sachs, MSS, MLSP [00:15:08]

OK. I’m going to let you keep going. Thank you.

Eleonora Teplinsky, MD [00:15:10]

All right, so let’s move on to immunotherapy.

Immunotherapy has been around for a while now, we use it in so many different cancers, but we really started using it in triple-negative breast cancer about 3, 4 years ago, longer if you were on a clinical trial. The idea with immunotherapy is that normally cancer cells are able to invade the immune system. The immune system does not recognize your cancer cells as foreign. And so the immune system doesn’t attack them. When you get sick, when you get a virus, your body’s able to say, “Hey, this virus doesn’t belong in the body.” And it attacks it and gets rid of it. It doesn’t do the same thing for our cancer cells until you give immunotherapy.

These drugs are called immune checkpoint inhibitors, and they essentially stimulate the immune system to attack the cancer. They stimulate the antitumor immune response, and the way they do that is by releasing the breaks that typically keep the immune system away. It stimulates that immune response, and it promotes the immune system to eliminate the tumor cells.

Very effective. But what can happen is sometimes the immune system gets excited and so then it can activate our normal T cells, which can attack and cause what is like an autoimmune disease. It kind of stimulates your own T cells to attack different organs. We’ll talk about some of the side effects in a second, but immunotherapy has 100%, if nothing else, revolutionized cancer outcomes. We use it in so many different tumor types. But let’s talk about how we use it in breast cancer.

A drug that many people may have heard of is Keytruda, or pembrolizumab. Approved in many cancer types. In breast cancer it is approved in two areas right now. The first is for metastatic, triple-negative breast cancer that is PD-L1 positive. These are biomarkers that will predict response to immunotherapy because of the way that the drugs target. It’s immunotherapy in combination with chemotherapy. That’s the KEYNOTE-355 trial. And then the KEYNOTE-522 trial in stage II to III, early stage, triple-negative breast cancer in addition to chemotherapy.

Now I can give you a whole talk for an hour on the KEYNOTE-522 study, but the idea is that immunotherapy very quickly became standard of care for stage II to III triple-negative disease because of a significant improvement in outcomes. And actually just last week or two weeks ago at the ESMO meeting in Barcelona, they presented 5-year overall survival data for the KEYNOTE-522 study. And 5 years is a really important marker, especially in triple-negative disease. What they showed was that, in people who received immunotherapy, 5% more were alive at the 5-year mark than people who did not receive immunotherapy. Nearly 87% of patients were alive at 5 years. We want to be at a hundred percent, we’re not there yet, we want to be more than 5 years. But this is still a very important milestone for this drug in this disease.

You do not need to be PD-L1 positive in early-stage breast cancer. That’s something that comes up a lot. And we are starting to see there’s some good trials in hormone receptor positive, HER2negative, this is the KEYNOTE-756 trial. And so we’re waiting on that data. We know that when we gave immunotherapy — similar to 522, but in hormone receptor positive — more patients had a pathologic complete response. Meaning that at the time of surgery more people had their cancer go away. But we don’t know yet if that actually translates to a lower risk of recurrence and a lower risk of dying from cancer. That’s what we’re waiting for before it gets approved and before we start using it routinely. But we’re making progress.

Eleonora Teplinsky, MD [00:19:44]

In terms of the side effects, I mentioned that the T-cells get activated, you get all these things that seem like, or are, autoimmune diseases. The most common thing we see with immunotherapy is thyroid. You should be, if you’re on immunotherapy, getting your thyroid levels checked very regularly, but it can affect any organ system. It can affect your brain, it can affect your heart, it can affect your intestines, your muscles, your joints, your bones, your kidneys, your lungs, your liver. And so we’re constantly monitoring. The challenge is people will say, “How do I know if a side effect is from immunotherapy or if it’s from chemotherapy?” And I will say sometimes it is hard to tell, but let’s say you’ve had 8 weeks of chemotherapy and you’ve had no side effects, and now all of a sudden you start having a ton of diarrhea, we want to make sure that that’s not inflammation of the intestines from the Keytruda. Sometimes you can’t tell. And sometimes if we can’t tell, we treat it with steroids and if it gets better then that can be a really helpful sign that it was immunotherapy related.

All right, Jean, any immunotherapy questions before we move on?

Jean Sachs, MSS, MLSP [00:20:58]

Yeah, I do have an immunotherapy question and then, I think I have a few more ADC questions.

Someone’s asking, if this person already has a history of autoimmune disease, is immunotherapy more likely to trigger an overreaction of an immune response?

Eleonora Teplinsky, MD [00:21:16]

It depends on what that immune disease is and how well controlled it is or not. A lot of people already have thyroid issues, that really isn’t a contraindication to treating with immunotherapy. But if you have a really uncontrolled autoimmune, even like an uncontrolled lupus where it’s flaring, then that may be a situation where we may not even give immunotherapy. These are individual discussions.

I will say that as immunotherapy has become much more commonly used, we’ve gotten more comfortable with using it. Years ago we might not have used it at all [in that situation] and now we’re trying to test and see, can we monitor it closely in conjunction with all of the other doctors that are caring for your immune diseases.

And this is where, especially for immunotherapy, working with all of our other specialists is so important because we’re going to use the cardiologist if you have myocarditis or inflammation of the heart, we’re going to use the GI doctor, the rheumatologist. So we’re working with all of our specialists here.

Jean Sachs, MSS, MLSP [00:21:25]

Got it. And so for the side effects from Keytruda, do they lessen over time?

Eleonora Teplinsky, MD [00:22:31]

On a day-to-day basis, most people don’t have many immunotherapy side effects. I will say some people feel occasionally a little bit nauseous, but day-to-day you really don’t have it. But when you have an immunotherapy-related event, it’s going to come out. Then we treat that, we usually will treat that with steroids. It’s not something where you have it every time. We don’t want that to worsen, so we’re going to treat that at really the earliest point.

Jean Sachs, MSS, MLSP [00:22:59]

OK. And if you’re doing well on Keytruda, it’s working, can you be on it for as long?

Eleonora Teplinsky, MD [00:23:07]

In the metastatic disease? Yes. I will say usually around 2 years. We typically don’t continue for more than 2 years, but there are of course exceptions. And then in the early-stage setting, right now it’s 1 year of Keytruda. It’s 8 cycles with chemotherapy before surgery and then 9 cycles after.

Jean Sachs, MSS, MLSP [00:23:29]

OK. And then this is a question about PD-L1. If their numbers are dropping, I guess they’re having less PD-L1, and they have triple-negative breast cancer. Should they still stay on immunotherapy? I don’t know if they’re metastatic or early stage.

Eleonora Teplinsky, MD [00:23:47]

Remember PD-L1 only matters for metastatic. We don’t usually keep rechecking it. As long as the immunotherapy is working we would continue it.

Jean Sachs, MSS, MLSP [00:23:59]

OK. So I want to ask just one ADC question. I’m not going to do a great job pronouncing the new drug that’s in the pipeline. Datto ...

Eleonora Teplinsky, MD [00:24:06]

Yeah, Datto is good.

Jean Sachs, MSS, MLSP [00:24:09]

Datto is good. So can you just share, what subtype is this looking at? And do you have a sense of when it might?

Eleonora Teplinsky, MD [00:24:19]

Yeah, it’s being looked at in a couple of different breast cancer disease types. It’s furthest along, believe, in the hormone receptor-positive, but there are some triple-negative studies as well. I do not have an idea of when it will be approved. Those decisions live with the FDA. So I don’t know.

Jean Sachs, MSS, MLSP [00:24:43]

Got it. All right, I’m going to let you keep going.

Eleonora Teplinsky, MD [00:24:46]

What I wanted to share is some ongoing trials for early-stage triple negative breast cancer.

The idea has been, if someone has a pathologic complete response with immunotherapy and with chemotherapy for triple-negative breast cancer, we know that a pathologic complete response is important. If you have that, do you really need to continue the Keytruda after surgery?

The OptimICE-pCR study is looking at actually taking away Keytruda, de-escalating, for people who have a pathologic complete response after neoadjuvant chemotherapy and immunotherapy. Participants on that study are randomized to either receive no treatment or pembrolizumab.

Now the OptimICE-RD study is the opposite. If you do not have a complete response, we want to continue the Keytruda but can we do something else? Obviously some cells were resistant, and we want to optimize our treatment to try to make sure if there are any residual cells that we can’t see, that we get rid of them. And the OptimICE-RD is just one of the several escalation studies that are out there.

Without a study, people who don’t have a pathologic complete response are typically getting, some will get pembrolizumab alone, some will get pembrolizumab plus Xeloda, which is an oral chemotherapy, and those who have a BRCA mutation will get Olaparib, a PARP inhibitor. And the studies are looking at novel drugs. The OptimICE-RD study is looking at sacituzumab govitecan which is Trodelvy, that’s an antibody-drug conjugate we mentioned earlier. Here we are now moving it into the earlier stage setting. And other studies are looking at different ADCs and different targets. I think these are really important studies because this is how we’re going to get better outcomes. We want to get close to a hundred percent of patients without a recurrence, and the more we can tweak and pivot and individualize therapies the better.

Eleonora Teplinsky, MD [00:26:55]

Let’s switch gears a little bit to CDK 4/6 inhibitors. These are drugs that are used in hormone receptor-positive, HER2-negative breast cancer. There is some data for using them for HER2-positive in the metastatic setting but not FDA approved, so we’re not going to touch on that. Those are smaller studies in very individual situations. Approved metastatic and early stage. Bottom line is that the CDK 4/6 inhibitors prevent cancer cell growth, they prevent cancer cell proliferation. And the way that they do that is by interfering with the cell cycle. On the right over here you see a picture of the cell cycle. There’s growth, the S-phase is DNA synthesis, G2 is more growth and then mitosis and they split into two. For all of our cells including cancer cells in the body, they have to grow and then they basically replicate into two. And that’s how more cells are made. The CDK 4/6 inhibitors block a key component of that transition between G1 and S in the cell cycle. And they do that by suppressing this phosphorylation of the retinoblastoma tumor suppressor protein. It’s a lot to say but in order for cells to go through the cell cycle, you need phosphorylation of this RB protein and the cells block that process. And so cancer cells can’t replicate and they die.

In the metastatic setting we have three drugs that are approved, palbociclib, which is Ibrance; ribociclib, Kisqali; and abemaciclib, Verzenio. In the early-stage setting we have two drugs that are approved. I’m going to focus more on the early stage because that’s a little bit newer. The drugs in the metastatic setting have been around for a long time. We do know that we’re seeing a little bit less use of Ibrance in the metastatic setting because some studies have come out saying that maybe Kisqali is better, but Ibrance is still very often used. And then we can pivot from switching from one to another if we need to. But let’s talk about the early stage.

Verzenio, or abemaciclib, has been around for longer. It is approved on the basis of the MonarchE trial. It’s approved for patients, all hormone receptor-positive, HER2-negative; they have to have four or more lymph nodes, or you could have had one to three lymph nodes and then either had grade three disease or a tumor size greater than five centimeters. Initially when it was approved, it was also approved based on a Ki-67 value. And that actually has been removed from the qualification to get Verzenio or not.

The study has been published several times and they keep publishing longer follow up, which is great because we know that these cancers can recur 5, 10, 15, 20 years down the road. So the longer follow up we have, the better. They’ve recently published a 5-year follow up and they found that patients who received abemaciclib with endocrine therapy compared to those who received endocrine therapy alone had a 7.6% absolute improvement. Meaning 7.6 more percent of patients were alive without a recurrence at the 5-year mark.

You can see in this graph, the bottom line in the blue is the people who got endocrine therapy alone. That’s 76% were alive without a recurrence at 5 years compared to 83.6% of people who got Verzenio. What’s interesting about this is that if you look, the benefit increases as each year passes. So there’s more of a benefit as you go later on because we know these cancers can recur kind of later down the road.

Verzenio is not the easiest drug to take. Some of the side effects include diarrhea, that’s really the biggest one. There’s also fatigue, low blood counts. With the diarrhea, people can have nausea, abdominal pain, there’s joint pain. And what’s difficult about this drug is that one or two episodes of diarrhea can really negatively impact someone’s quality of life. This is where many people require a dose reduction. And there was a study actually published just a few months ago that said, which is so reassuring, that if we dose reduce, we are not compromising the efficacy of the medication. And that’s huge because one of the questions people ask me all the time is, “If I lower the drug because I’m having side effects, am I going to lose its effectiveness?” And we have clear data to show that it does not do that. That’s abemaciclib.

Eleonora Teplinsky, MD [00:31:57]

Just last week, so this is hot off the press, ribociclib was approved also in early-stage breast cancer. And this is on the basis of the NATALEE trial. So the NATALEE trial, same idea in terms of endocrine therapy alone, here just with an aromatase inhibitor, or adding ribociclib to that aromatase inhibitor. Now the approval for ribociclib, and I have it here, is broader than that for abemaciclib. Abemaciclib is a very high-risk population, meaning people at the highest risk of a recurrence. And within that there’s variation. Ribociclib allowed, if you were lymph node-positive at all, you were able to go on the study. You didn’t need all those other things. If you were lymph node negative, then I have that here, you had to have grade III disease or grade II, and there’s all these characteristics, but the idea is that it allows for a broader population.

We have data, it was originally presented in June of 2023. And at that point they said if you add ribociclib, you have about a 3% benefit in reducing risk of recurrence or death from breast cancer. And just last week they presented the 4-year updated data and similarly that 3% jumped to 5%. So we’re starting to see again that longer benefit as time goes on. The big thing here is that it allows patients that are lymph node negative. So based on studies it’s estimated that double the amount of patients will qualify for ribociclib than qualify for abemaciclib.

This is a really important medication. It gives a lot more options to people, but as always it comes with side effects. Some of the most common side effects are low blood counts. We have to monitor the blood counts closely, joint pain, nausea, headaches, fatigue. I will say that ribociclib is a little bit easier to tolerate than abemaciclib. It does require EKG monitoring for the first several visits because it can cause arrhythmias. And we really want to monitor the liver enzymes.

Now Verzenio is given for 2 years with endocrine therapy. Ribociclib is given for 3 years. And so it’s a discussion because it’s 3 years of more intense visits and more intense following and more intense side effects. And so these are all really risk-benefit discussions with patients and their doctors. The nice thing about ribociclib is that the dose approved in early stage is lower than the dose approved in the metastatic setting. So I think we’ll even see some better tolerability, which is really important.

Before we move on to the next group of medications, let’s stop here for any questions.

Jean Sachs, MSS, MLSP [00:34:57]

Yeah, we do have some questions.

One person is asking if Kisqali has an interaction with the approved medication for menopausal symptoms Veozah?

Eleonora Teplinsky, MD [00:35:14]

Not that we know of. One of the things that I did not mention is that ribociclib cannot be given with tamoxifen. It can only be given with an aromatase inhibitor. There is an interaction there. I will say with any medication you always want to check, and I do this all the time. When I’m seeing patients, I’ve got my drug interaction calculator up, and I’m always confirming and checking because there are so many drugs out there. We do want to check, with ribociclib, we want to make sure with certain drugs that there is no metabolism interaction, there’s certain foods. So definitely talk to your doctor about just making sure that everything is OK.

Jean Sachs, MSS, MLSP [00:35:52]

OK. And then in the metastatic setting, if you started on Ibrance and the cancer has progressed, can you move on to another CDK 4/6?

Eleonora Teplinsky, MD [00:36:01]

Yes, there are studies that look at this. It’s, I believe, the MAINTAIN study and the postMONARCH study. They look at CDK after CDK, and that is an option. What we want to do, and I know you have a whole separate talk on this, is molecular testing of the tumor because we want to see are there other mutations we can target with different medications. But yes, you absolutely can give another CDK 4/6 inhibitor if you’ve previously been on one.

Jean Sachs, MSS, MLSP [00:36:28]

OK. And then in the early-stage setting, there’s a lot of questions. If the efficacy for Verzenio is still good at a lower dose, why are so many people being put on the higher dose? And how do you have that conversation upfront?

Eleonora Teplinsky, MD [00:36:43]

It’s a great question and the best thing I can tell you is that the study looked at the efficacy for people who had to dose reduce based on side effects. We don’t have a study looking at starting everyone on a lower dose. And so we don’t know if that efficacy is going to be the same. Dose reducing for symptoms versus starting everyone on a lower dose is a different question. And so I have that conversation, I explain that to patients and I will say I have some patients that I know they had a hard time on, let’s say chemotherapy, they’re prone to diarrhea, we’re not starting at the full dose. On the other hand, I have some people who do great on that full dose and other people who go right away down to the lowest dose. So everyone is different.

And I think we’re seeing our patients so often, I will change it. I think the key is to be upfront about your symptoms and not to say, “Oh, I’ve got three episodes of diarrhea, I can handle it.” Yes, you can handle it, but do you have to? Maybe your quality of life would be better with one or none.

I think it’s that conversation, but you’re right that that’s a common question that comes up and we just don’t have that answer.

Jean Sachs, MSS, MLSP [00:37:59]

Right. So it’s so important. Have a great relationship with your doctor, and if you don’t, get a second opinion.

I’m assuming this question’s coming from a metastatic patient. If a medication stops working and the cancer progresses, can you ever go back to that medication at some point in time?

Eleonora Teplinsky, MD [00:38:17]

Yeah, it depends on what the situation was. Sometimes we’ve rechallenged after a while, but a lot of it depends on what was the progression, how long were you on it, what happened to the disease at that point, how did you tolerate it. It’s not a blanket statement one way another.

Jean Sachs, MSS, MLSP [00:38:36]

OK. All right. I’m going to let you keep going. Thanks.

Eleonora Teplinsky, MD [00:38:39]

All right. So we’re going to move on to our last category here, which is novel endocrine therapies. This graphic makes my head hurt, but the idea is to show you that there are so many next-generation endocrine therapies being developed both for early stage and metastatic. This is really great because what we have right now, and I’ll tell you about a new one that’s been approved, but everyone in early stage is either on tamoxifen or they’re on aromatase inhibitors and the side effects are really profound for many people. People are in a very low-estrogen state. They’re living with those toxicities, and they’re really debilitating for many people. Additionally, we know that people do develop disease recurrence despite being on these medications. There’s really been a need for agents that overcome these mechanisms of resistance, that still are able to target the endocrine receptor so that we don’t have to switch to chemotherapy but overcome that resistance and hopefully improve some of the toxicity and the side effects.

There’s many in development, they all focus on really targeting the estrogen receptor. So SERMs are things like tamoxifen that don’t get rid of estrogen in the body but modulate the receptor. Then we have SERDs, this is fulvestrant, or Faslodex. There was a new one approved recently, elacestrant, which I’ll talk about. These degrade the receptor. And then there’s PROTAC and CERANs and SERCAs which all modulate the receptors in different ways.

Eleonora Teplinsky, MD [00:40:23]

The nice things that they’re doing is they’re not degrading estrogen. So toxicity, we hope, is going to be less of the side effects that come from that low-estrogen state. And there are many, many in development. Every review article that you look at, it’s a table, a page or two long, of all of the novel endocrine therapies in development. I think this is a field that’s really going to explode hopefully in the next few years.

Now elacestrant, the trade name for this is Orserdu. This is an oral SERD. This degrades the receptor — so it doesn’t get rid of estrogen, it just degrades the receptor — and it’s an oral medication which is always a good option. And this was approved in January 2023 for post-menopausal women or men with hormone receptor-positive metastatic breast cancer who had previously been on at least one prior endocrine therapy, and they all had to have had a CDK 4/6 inhibitor and you had to have an ESR1 mutation. Now ESR1 mutations tend to tell us that patients may be resistant to aromatase inhibitors. We’re not using ESR1 mutations yet in early stage, but they are really important in the metastatic setting. This is why molecular testing is important. ESR1 mutations can arise at any time. So when someone develops disease progression, we’re always checking to see has an ESR1 mutation developed.

This medication, the oral elacestrant, reduced the risk of disease progression or death from breast cancer by about 30%, but then by about 45% in patients with ESR1 mutation. So it was approved for that cohort with ESR1 because that’s where the benefit is the greatest.

Side effects are there, mostly what I have seen is nausea, fatigue, vomiting, and some other GI side effects as well. As you can see here, headaches, hot flashes. The big one that we monitor is lipids, your cholesterol. We monitor as a baseline and then throughout treatment because here’s where the lipids can go up very quickly on this medication. So this is where working with your doctor or maybe a cardiologist is important. And I will tell you what I do in the clinic is if I think someone’s going to start on that medication soon, I’m already checking their lipids, I’m sending them to the cardiologist to optimize everything before we even start the medication if that’s possible.

Now these are really two trials I’m very excited about in early-stage breast cancer. These are SERD, these are the selective estrogen receptor degrader trials. So we’re not blocking estrogen, we’re getting rid of the receptor. And we’re moving these drugs from metastatic studies to early stage. The one on the left is the CAMBRIA-2 trial. This is looking instead of endocrine therapy, this is for patients on who have a high risk of recurrence. You can see on the left the criteria. They’re going to get the SERD camizestrant. And if they qualify they would get abemaciclib as well. Now this study was approved and started before ribociclib got approved. Sometimes they amend the studies to allow ribociclib, I don’t know what’s going to happen here. But in any case, so endocrine therapy or camizestrant.

On the other hand, the EMBER-4 trial is a different SERD called imlunestrant. And this is for patients who already had 2 to 5 years of endocrine therapy and have a higher risk of recurrence. They’re going to be switched to either continue for 5 more years of endocrine therapy or switch to 5 years of the imlunestrant. The reason that these are patients at a higher risk of recurrence is we’re hoping that these novel medications circumvent some of the mechanisms of resistance to aromatase inhibitors. But it’ll also be really interesting what we see in terms of toxicities and side effects. And hopefully the side effects will be better, but only time will tell for that.

In conclusion, and I’m happy to answer questions, breast cancer treatments, as you can see, are rapidly evolving. We have so many innovative therapies, and we’ve changed our treatment options. We’re improving outcomes, but we still need to focus on managing side effects, improving tolerability, so that we can maximize the benefits of these therapies. Because if we have these medications but people can’t tolerate them or their quality of life is impacted, then I don’t think we’re getting the most out of them that we can. And of course continued research and clinical trials are essential for the future and for the expanding options for all of our patients.

I think we have 10 minutes, so I’m happy to answer as many questions as we can.

Jean Sachs, MSS, MLSP [00:45:29]

You did an amazing job. You’ve timed it perfectly.

A question I have is with all these new developments — which are so exciting and I think SERDs and PROTACs really — there’s so many comments about the side effects of AIs, and we’ve known that for a long time. Do you feel like this is being pushed out throughout the country to everybody, even people who are seeing a general oncologist, not necessarily an oncologist that specializes in breast cancer?

Eleonora Teplinsky, MD [00:46:02]

I think that’s a great question. The trials are not open everywhere, so I think it depends on if the trial is open by you, and I think that speaks on a greater level to the need to make sure that we have trials in the community. So often, trials are limited to bigger centers, and it’s impossible for patients to get there. And the parking and it’s a 3 hour drive. I think it really speaks to the importance of we need to get patients these trials in the community.

I think it’s variable depending on where in the country you are, and if that study is open. And I will say we don’t know. ... The goal is to test the effectiveness of these medications. This is a trial, we still don’t have the answer of how effective is it going to be. And that’s what these trials are attempting to answer. There’s always some hesitation and questions being asked. I will tell you I get questions all the time, people reach out to me and say “I’ve been approached about CAMBRIA or EMBER, what should I do?” And I think the answer is these are questions we need to answer.

Jean Sachs, MSS, MLSP [00:47:14]

OK. And cami and Truqap are the same, is that right?

Eleonora Teplinsky, MD [00:47:19]

No. Camizestrant is not.

Truqap is capivasertib, which is a drug with fulvestrant for metastatic patients who have a PI3CA, AKT, or PTEN mutation.

That’s capi [capivasertib or Truqap].

That’s cami [camizestrant].

Different.

I don’t think camizestrant has a brand name yet, but I could be wrong.

Jean Sachs, MSS, MLSP [00:47:41]

OK. Why is the GI system so impacted by these CDK 4/6 inhibitors?

Eleonora Teplinsky, MD [00:47:49]

I think that’s just sometimes where the targets are. We know that it can also impact the blood counts. Those are just cells that have those markers and that are a little bit more affected by the CDK 4/6 inhibitors based on how they target.

The challenge for any drug is that they target both our normal cells and our cancer cells. And if the normal cells have that receptor, they’re going to kind of target those as well. And I do think the drugs are all different. Ribociclib does not have as much of the GI toxicity that abemaciclib has. Ribociclib, we tend to see more liver enzyme elevations. We tend to see more lower blood counts than we see with abema. So they are slightly different drugs because they’re all CDK 4/6 inhibitors but one does more CDK4, CDK6, they all have slightly different targets.

Jean Sachs, MSS, MLSP [00:48:42]

Thank you.

We get this question a lot. There are some people asking what is metastatic breast cancer? If you have involvement in your axillary nodes, is that considered metastatic?

Eleonora Teplinsky, MD [00:48:56]

Great question. It’s not. Metastatic breast cancer is breast cancer that has spread outside of the breast and the axilla, or the armpit.

Where this comes up often is that the pathology report will say metastatic to the axilla, and so of course you’re thinking, “Oh my gosh, do I have metastatic breast cancer?” But when they say metastatic to the axilla, it means it’s spread to the axilla. But that’s not metastatic breast cancer. Metastatic breast cancer, one more time is cancer that’s outside of the breast and outside of the axilla.

Jean Sachs, MSS, MLSP [00:49:27]

Right. Thank you. And then what about long-term side effects? I know we think about this a lot, but this person is specifically asking about long-term side effects of Herceptin and Perjeta.

Eleonora Teplinsky, MD [00:49:37]

Yeah, I think that’s a really great question.

We know that Herceptin and Perjeta can affect the heart. That is typically a temporary and reversible side effect. While you’re on any HER2-based therapy, you’re getting an ultrasound or an echocardiogram of your heart on a regular basis. Typically for Herceptin and Perjeta, we do that every 3 months. And the reason that they can affect the heart is that there are HER2 receptors on your heart. So the Herceptin not only binds to the cancer cells, but it can also bind to those HER2 receptors on your heart muscle. But that is typically a reversible toxicity.

We’re looking at your ejection fraction, which think of this as how effectively your heart pumps out blood to the rest of the body. If your ejection fraction drops or you develop symptoms of heart failure, shortness of breath, swelling of the legs, we interrupt the Herceptin and Perjeta. We hold it, typically for about a month, and we repeat the echocardiogram and the majority of the time that is a reversible side effect.

Typically, we don’t really see that long-term cardiotoxicity from Herceptin and Perjeta. It’s more what we see while you’re actually getting the medication.

Jean Sachs, MSS, MLSP [00:50:49]

OK, that’s helpful.

This is an early stage question. When do you think some of these new endocrine therapies that would replace tamoxifen or AIs might be available?

Eleonora Teplinsky, MD [00:51:04]

I think we’re a while away. We get excited because the trials are really exciting. But this is the challenge with early-stage trials. They are looking to accrue thousands of patients.

So number one, you have to accrue these patients and that takes time. It’s different than in a metastatic trial where maybe you’ve got 200, 300 patients, it’s easier to accrue. Lots of patients, number one.

Number two, you have to wait to see if there’s going to be a benefit. For example, you have to show that less people have a recurrence on the newer medication depending on what their outcomes are. To give you an idea, the Verzenio studies really started, I would say 2016, 2017. And I think it was approved in 2022. It’s at least, I mean it’s a couple of years. Same thing, NATALEE was a study ongoing 2017, 2018, just got approved, ribociclib. I think we’re at least 5, 6 years away. I would love to be completely wrong, but I don’t think it’s something that’s going to happen in the next 2 to 3 years.

Jean Sachs, MSS, MLSP [00:52:14]

And if people are interested in learning more about these trials and maybe joining, what do you suggest they do?

Eleonora Teplinsky, MD [00:52:21]

So one is talk to your oncologist. The other way to take charge and advocate for yourself is go to clinicaltrials.gov. You can also just search CAMBRIA-2 and EMBER-4 and it’ll give you where they’re accruing. But on clinicaltrials.gov, it’s not the best, easiest website to navigate, but you can put where you’re located, you could put your disease type and see what’s out there. And so you can type in EMBER-4 because that may be, if you’re already on endocrine therapy, EMBER-4 may be the better trial for you. And you could see where it’s open and reach out to that facility.

Jean Sachs, MSS, MLSP [00:52:58]

Great. I’m going to ask one more question and then we’re going to have to stop. But this person has asked a couple of times, so they want to understand. What are the side effects from starting Lupron injections?

Eleonora Teplinsky, MD [00:53:08]

Well, Lupron essentially is putting you into menopause. I like to think of it as a switch. It’s turning your ovaries off. The way it’s doing that is by kind of tricking your body into thinking that it’s making too much estrogen. And your ovaries should shut down as a result of that. I have a lot of videos on my Instagram about Lupron that you can check out.

So Lupron puts you into menopause, and the side effects that come are typically menopausal side effects, if you’re not already in menopause. Hot flashes, joint pain, vaginal dryness, mood changes. Now it doesn’t mean that everyone on Lupron is going to get those side effects, but these are things that may happen and we do have really good ways to manage these side effects.

Jean Sachs, MSS, MLSP [00:53:52]

Thank you so much. We could probably ask Dr. Teplinsky questions all day, but the good news is you can find her on Instagram. Can you tell everybody your Instagram handle?

Eleonora Teplinsky, MD [00:54:04]

Yes. It’s @DrTeplinsky, super easy. You just type in my name, and it’s there. I have a ton of stuff on there. I do a ton of Q&As. If you have a question, most likely I have a video or something on it already.

Jean Sachs, MSS, MLSP [00:54:18]

That’s amazing. And it’s just so great that you make yourself so accessible.

This was a wonderful session. So I want to thank you for your time. I’m sure you probably have to get back to the clinic.

Session 3 | Understanding testing in breast cancer

Reshma Mahtani, DO [00:00:09]

Thank you to the team at LBBC for inviting me here this afternoon. And thank you to all of you for sharing the next hour with me as we go through this very important topic of understanding testing in breast cancer.

As we all know, anyone can develop breast cancer. One in eight women will get breast cancer in her lifetime, and, although much less frequently affected, men can also develop breast cancer.

The good news that we’ll start with is that trends in female breast cancer death rates are falling, and they’re pretty consistently falling. This slide shows the death rates by race and ethnicity, and recognizing that there are clear disparities in care and Black women especially are at a higher risk of dying of breast cancer. As we know, these disparities are very important to address. What I would like to focus on is a bit of good news in that the overall rate in 2020 declined by 43% from its peak in 1989, and that equates to a considerable number of breast cancer deaths that have been averted. So how are we making this progress?

A lot of the progress has been made on the basis of getting the word out about the importance of early detection, finding cancers at a smaller size, and without lymph node involvement or finding stage I and earlier stage II cancers. It definitely equates to improved outcomes and an increased chance of cure. But also these improvements in death rates are very much the result of improvements in our therapies. And our therapies are very much based the testing that we put patients through and tumors through. That’s what I want to focus on today.

By way of background, I want to share this news that for early-stage, localized cancers, the overall 5-year survival rate is very high, 99%. For regional cancers, meaning larger tumors with lymph node involvement, we’re still making considerable progress, but, again, finding these cancers at a smaller stage or earlier stage is very much linked to improved outcomes.

Now let’s focus on treatment and talk about testing. But first, let’s talk about the therapies that may offered on the basis of some of the testing that I’ll be reviewing with you today.

Treatment is based on the type of breast cancer and its stage. Of course, we take into account your overall health. Menopause status and personal preferences are, of course, considered. Many times in the early-stage setting we’re including local treatments, such as surgery and radiation, as part of the therapy. It’s not an absolute that those treatments are not part of a treatment plan for a stage IV, or metastatic, breast cancer patient, but more often the therapies in the metastatic setting focus on systemic treatments, such as chemotherapy, hormonal therapy, targeted drug therapy, and immunotherapy. As a medical oncologist, my focus is in giving these systemic treatments to either stage IV breast cancer patients or, in certain situations, to high-risk, early-stage breast cancer patients in an attempt to reduce the risk of recurrence.

Let’s get into the topic at hand, testing, and let’s talk first about the different types of testing that you may be offered during your treatment journey.

In the beginning we often do baseline blood work to assess kidney and liver function and monitor blood counts as well as side effects. We can use the blood work to monitor side effects and organ function. And then, of course, imaging tests are very important, like CT scans, MRIs, PET scans, and bone scans, to track response to treatment and detect progression. This is used in the metastatic setting, but even for early stage patients, when we’re trying to understand whether the cancer may have spread at initial diagnosis there may be an indication to do some of these tests. Some of our medications can cause side effects, especially with regards to the heart, and that’s why there may be the need for an EKG or an echocardiogram. Those are cardiac monitoring tests.

Reshma Mahtani, DO [00:05:24]

And then there are opportunities to do other sorts of specialized tests called liquid biopsies where we’re tracking, in the bloodstream, fragments of DNA, circulating tumor DNA, that has been released into the bloodstream. We’re identifying on those blood tests mutations that may be present in the cancer that could help us track treatment response. And again, that’s very much utilized in the metastatic setting.

Genomic profiling is an important aspect of treatment where genes are analyzed in the tumor, as well as proteins, to identify specific mutations, which may be targeted. And then, of course, tissue biopsies are very important to analyze not only mutations that evolve that may impact treatment, but baseline tests on those tissue biopsies. For example, we’ll go through, in the next slide, one of the major factors that we use to inform what we offer in terms of early-stage and metastatic treatment. But that’s based on the subtype of breast cancer. Again, this is based on a tissue tumor biopsy.

Broadly speaking, in the early-stage setting, we’re thinking still of our breast cancer diagnoses as one of three subtypes. Recognize that breast cancer is not one disease, there are multiple subtypes. The most common is hormone receptor-positive breast cancer. And I’ll be focusing a lot of my discussions when we come to testing on this subtype of breast cancer. But recognize that about 10% to 20% of breast cancers are so-called HER2-positive. These tumors depend on this gene, HER2, to grow, and it is a somewhat more aggressive subtype of breast cancer. But the good news is we’ve made considerable progress in treating this subtype, and we’ve improved outcomes greatly. A lot of the declining death rates for breast cancer have been attributed to our improvements in treating HER2-positive disease.

And then triple-negative breast cancer, meaning these tumors do not depend on estrogen or progesterone or the HER2 gene. Those are three negatives; we call that triple-negative breast cancer. Accounting for a smaller minority of breast cancers but tend to happen more often in younger women and particularly Black and Hispanic women.

In the early-stage setting, when you have a breast cancer diagnosis, one of the first things to try to get a sense of is which subtype of these breast cancers do you have. And that can be reviewed with your oncologist or your surgeon based on a pathology report.

Now let’s dive into this a little bit deeper. A lot of people get confused about this terminology, hormone receptor and estrogen receptor. Hormone receptor-positive is a broader term, but it encompasses ER-positive or PR-positive. Tumors can be ER and PR positive. They can be ER-positive and PR-negative. Very infrequently they can be ER-negative and PR-positive. But if either of these two receptors are positive, we call it a hormone receptor-positive tumor, which means that the cells have receptors for the hormones estrogen and progesterone, and it means that the cancer can be stimulated to grow by these hormones. About two-thirds of all breast cancers are hormone receptor-positive, so it’s very much the most common type.

Now what about HER2? We’re going to talk about HER2 a lot, especially when we get to the metastatic setting, we’re going to circle back with this new term called HER2-low disease. But in the early-stage setting, we’re not utilizing HER2-low status very much. We’re still considering tumors HER2-positive or HER2-negative in the early-stage setting.

Reshma Mahtani, DO [00:09:55]

What is HER2? HER2 is a protein that’s located on the cell surface, and it’s involved in normal cell growth and development. An overexpression of this protein on cancer cells leads to aggressive tumor growth. You see a normal cell on the left, normal HER2 expression. All the way on the right, you see what we call a HER2 3+ tumor, that’s moderate-to-high HER2 protein expression. And then you there is a continuum: 0, 1+ and 2+. Now the 2+ is considered indeterminate, and additional testing needs to be done to identify whether that tumor is HER2-positive or not. But generally speaking, HER2 1+ and 0 is considered HER2-negative in the early-stage setting. And 2+, with that additional testing, could either be HER2-positive or HER2-negative.

We’re talking about testing, and so far we’ve talked about the importance of ER, PR, and HER2 and recognizing that those markers very much drive the treatments that we can offer. What is an additional piece of testing that is very important is your family history.

When we think of breast cancer, I see this or hear this in my practice quite often, “I don’t understand how I developed breast cancer. I have no family history.” Most women who develop breast cancer don’t have what we call a hereditary type of breast cancer that developed because they inherited a gene that was mutated from their mom or their dad. Most are considered what we call sporadic-type breast cancers, but about 5% to 10% are on the basis of a gene that was inherited from your mom or your dad. And that gene is mutated. These hereditary breast cancers are associated with younger age at onset, triple-negative more frequently but not always, even hormone receptor-positive, HER2-negative breast cancers can be on the basis of a germline genetic mutation.

It’s important because if you harbor one of these mutations, there are additional cancers that you may also be at risk for developing. And as I’ll show you, it impacts not only how you will be monitored but now more recently also impacts treatments that you could receive in the early-stage as well as metastatic setting.

There are several genes associated with hereditary breast cancer, and notice a big portion of this pie chart is kind of vague. It says “other genes” and “familial risk factors.” That is alluding to the fact that we don’t know the entire story in certain families. I’ve seen many patients in my practice who have very, very strong and suggestive family histories, and we’ve not identified which gene may be involved in their specific family. The most common that we see and that we know are hereditary gene mutations that can increase the risk of breast cancer are BRCA1 and BRCA2. But as you see, there are a variety of other gene mutations that can inform your risk of developing breast cancer.

Let’s focus on BRCA a little bit because it is the most common. What is a BRCA mutation and why does it matter?

BRCA genes are found on chromosome 17 or 13. as shown here, BRCA1 and BRCA2. And as we talked about in the first slide, one in eight, or around 12%, of women will develop breast cancer at some point in her lifetime. You see those risks going up markedly with the presence of a mutated BRCA1 or BRCA2 gene as shown for you in the left lower hand portion of the slide.

These mutations affect the cell’s ability to repair DNA, and if you have this mutation, you have multiple options to reduce your risk of developing a future breast cancer and to decrease your risk of developing other cancers like ovarian cancer. You see some of those options here.

Reshma Mahtani, DO [00:14:45]

Most importantly, there’s a 50% chance of passing it on. You see in the picture on the right, in pink, the father in this case is affected. This is another common misconception, that only women can have an issue with a mutated BRCA gene. Men can as well, and there’s a 50-50 chance, as you see, there’s an affected son and an affected daughter in this case, on the lower right-hand side. Men are affected and they can develop breast cancer. If you see a man who has breast cancer, genetic testing is absolutely recommended, but can it can also increase the risk of prostate cancer and pancreas cancer.

Other breast cancer genes with medical management guidelines are shown here. Again, we focused quite a bit on BRCA1 and 2. I won’t take you through all of this right now, but I will show you that the risk that is present with these genes is variable, as shown for you in this table. There is a different level of data to support preventive surgery, preventively removing the breasts, based on which gene mutation is present. There are guidelines that impact how you should be monitored for developing breast cancer, to include a breast MRI as well as the traditional monitoring with mammogram every 6 months, and a variable risk of other cancers. So this information is important.

I would also add that now we have the availability of a drug called a PARP inhibitor. It is a pill. If you have a BRCA mutation and you have early-stage breast cancer, if your tumor was a certain size and had a certain amount of lymph node involvement, you may be eligible to take that medication. It has been shown to reduce the risk of the cancer coming back and also has shown a survival benefit. So this information is key to ask about in terms of testing.

A couple other words on genetic testing. In a given family, the affected individual is the most appropriate person to test for the presence of a germline mutation. Testing the affected family member first will establish if there is a detectable mutation in a known cancer risk gene. And this provides more informative testing for unaffected family members. If an affected individual tests negative, this may eliminate the need to test multiple unaffected family members and save resources. But this would be an individual discussion with the genetic counselor. You may still meet criteria to undergo testing.

Of course, if an affected individual tests positive, this may explain the cancer history in the family and provide unaffected family members who test negative reassurance that they didn’t inherit the cancer risk.

So genetic testing is an important aspect of testing, especially in the early-stage but also in the metastatic setting, where guidelines indicate that all women with metastatic breast cancer should be offered genetic testing. Genetic testing guidelines have recently been changed, every woman with a breast cancer diagnosis who’s less than 65 should consider genetic testing. And based on other factors, individualizing testing recommendations for women over 65 with a breast cancer diagnosis is also recommended.

I want to spend a moment talking about these terms, genetics versus genomics, because in my practice people are confused about this constantly.

The testing that we’ve been talking about in terms of BRCA and the other genes I showed you in that table, that’s considered germline genetic testing. Those are genes that could be mutated that would have been inherited from a parent and could be passed on to a child. And genetics is the study of individual genes and inheritance.

Genomics is the study of multiple gene functions and interactions with each other and the environment. For example, I spoke with you about HER2, that is a genomic test on the tumor. That’s a gene, but it doesn’t mean that it’s something that can be passed on to a family member. That is genomic testing on the tumor. ER, PR, HER2 is all genomic testing. And we’ve moved into an era of very sophisticated genomic testing, including gene expression and next-generation sequencing. And we’ll talk a little bit about that more when we get involved in the discussion on metastatic disease.

Reshma Mahtani, DO [00:19:50]

Just to finish up the early stage, I want to talk about one other aspect of testing that is important. I’ll just take a big step back and talk about, broadly speaking, the three different treatment decision points in the early- stage, hormone receptor-positive breast cancer patient’s journey. I’m only focusing on hormone receptor-positive because it’s the more common subtype. This journey may look different for a triple-negative breast cancer patient and a HER2-positive breast cancer patient. And certainly tests to identify whether or not HER2-directed treatment would be of course recommended in that journey and pathway may look very different. As it would for a triple-negative patient, where we have the use of immunotherapy and chemotherapy now routinely in the early-stage setting.

Focusing on hormone receptor-positive in the initial diagnosis, usually surgery is done first. There are only selected cases where we consider preoperative treatment, but in the usual case you go for surgery first. And the decision is do you need chemotherapy and hormonal or endocrine therapy or is endocrine therapy alone sufficient. There’s also now the availability of these two drugs called CDK 4/6 inhibitors. These are therapies that were initially approved for stage IV, metastatic patients and now in high-risk, early-stage breast cancer patients can be taken for either 2 or 3 years, depending on which drug is chosen. And in addition to the chemo and endocrine therapy, those drugs have shown further reductions in the risk of relapse.

Then there’s this time point of 5 years. Most women take hormonal therapy for 5 years. It’s very important to note that 50% or more of the recurrences actually happen after that 5-year mark. With that in mind, there is the opportunity to consider longer durations of hormonal therapy. I bring up these decisions because the focus of the presentation is testing. So how does that factor into testing? There are tests that can be offered, these are tests on the tumor, that can help us make these decisions. You may have heard of these tests, Oncotype, MammaPrint. These are tests that help us make that first decision about does chemotherapy help reduce the risk. They provide prognostic information, meaning: What is my risk of recurrence?

And some of these tests also provide predictive information: What is my benefit of taking a certain therapy? Either chemotherapy, or in the case of the Breast Cancer Index, this test can help understand what your risk is if you were to stop the endocrine therapy at 5 years and whether there would be a benefit to continue to 10 years. And of course there are other tests as well.

The summary of the testing in early-stage breast cancer, I hope that I’ve driven these points home to you: Genomic tests, including ER, PR, and HER2, these very much guide our choice of therapy. Gene expression assays, like the one I just ones I just showed you in the previous slide, can help make decisions about the use of chemotherapy and the duration of endocrine therapy. An informed discussion regarding germline genetic testing based on a personalized risk assessment, taking into account the age of diagnosis, your specific family history, your specific type of breast cancer, these are absolutely things that should be discussed with your physician at diagnosis.

With that I’m going to pause. We’re at the halfway mark, so this is perfect timing to ask if there are any questions.

Jean Sachs, MSS, MLSP [00:24:15]

Thank you, Dr. Mahtani. You did a great job, and you’ve actually answered a lot of the questions. I’m going to hold the genomic testing questions, so I’m just going to ask a few on this.

One thing you didn’t touch on is the Signatera test.

Reshma Mahtani, DO [00:00:09]

That’s a great question. I’m glad that somebody brought that up.

This is a test that has been marketed quite a bit to patients directly. Just so that we all are on the same page in terms of how this information helps, there are fragments of tumor DNA that can be spilled into the bloodstream and can be picked up at a very low level, much more sensitive than PET scans and bone scans and CT scans. And this is a type of testing that has the promise of finding cancer when it has come back earlier than when we can see it on imaging studies.

It’s a very sensitive tool and it gives us a lot of information about prognosis, risk of recurrence, but it’s not a hundred percent accurate, that sensitivity is not a hundred percent. Just because you have that positive signal doesn’t mean there’s a hundred percent risk that the cancer will come back.

Additionally, and most importantly, the part that we all are struggling with in practice is what does it mean if it is a positive test. Does it mean that we should intervene in some sort of way? What should we intervene with? How many cycles of whatever treatment should we give? And are we actually impacting recurrences or are we just exposing people to more therapy, more toxic treatments and side effects?

Until the trials are complete, and multiple studies are ongoing to test the intervention of using tests like Signatera and others, we’re not routinely recommending, outside the context of a clinical trial, for this sort of testing to be done.

Jean Sachs, MSS, MLSP [00:26:34]

Great, that’s helpful. So the name of the test is Signatera, and the company is Natera. Some of the participants are using those names interchangeably, but they’re the same.

There’s a number of people who are, not surprisingly, struggling with side effects from either their AI or tamoxifen. When would it make sense to maybe do the MammaPrint or the Prosigna to see if there is benefit for continuing hormonal treatment?

Reshma Mahtani, DO [00:27:07]

The test that helps make that decision about continuing endocrine therapy to 10 years or not, the one that’s been endorsed by the guidelines, is actually the Breast Cancer Index. And typically that test is offered around year 4.

I should tell you that in the setting of more than three positive nodes, it wouldn’t be appropriate to order the test. It’s not been validated to support decisions in that situation. If you have more than three positive nodes, the recommendation is usually to extend to 10 years.

But around year 4 is when I start talking to my patients about it because it can take some time to track that tissue down and send it out to the company and for the results to come back. We try to make these decisions not in a rushed way. So somewhere around year 4 you could consider talking to your medical oncologist about ordering it if they feel comfortable and they feel it’s appropriate.

Jean Sachs, MSS, MLSP [00:28:12]

That’s helpful. And there are other companies that talk about the benefit of their test. So important to talk to your doctor about which test is appropriate.

I think it’s worth talking about this, although it might come up in the genomic testing section. We’ve made a lot of progress with liquid biopsies, and it’s made it a lot easier. So if you could sort of talk about that, not having to do a tissue biopsy.

Reshma Mahtani, DO [00:28:42]

In the metastatic setting we’re going to talk about that quite a bit because for the early-stage setting tissue biopsy is still our standard. At the early-stage diagnosis we’re talking about confirming that whatever is going on on imaging or on exam is indeed breast cancer and confirming those important markers, ER, PR, and HER2.

Liquid biopsies in the early-stage setting are not routinely being utilized. It’s in the metastatic setting where that information is so important because it can give us clues about possible next treatment options. And we’ll talk about that in the next section.

Jean Sachs, MSS, MLSP [00:29:27]

Great. And then just to clarify for a participant: If you’re HER2-positive, these tests about stopping, I mean I’m assuming they’re HER2-positive and ER-positive but I don’t know, do these tests about potentially stopping endocrine therapy apply to them?

Reshma Mahtani, DO [00:29:44]

That’s a great question. The data with some of these tests in ER-positive and HER2-positive, we call that triple-positive tumors, the data is not as strong to utilize these tests. About 15% or less of patients that were enrolled on trials that validated the use of tests like Breast Cancer Index had HER2-positive and ER-positive disease.

That being said, the smaller data sets that we have do point to a possible role even in ER-positive, HER2-positive patients. That’s an individual discussion with your physician, whether he or she feels comfortable utilizing it in that way.

Jean Sachs, MSS, MLSP [00:30:28]

Great. I’m going to ask one more question and then we’ll go to the next section.

If you’ve made it to 10 years, is there any need for additional testing after that?

Reshma Mahtani, DO [00:30:38]

Recognize that even in the first 5 years after an initial diagnosis, our guidelines do not call for any routine tests to be done. And certainly the farther away that you get from that initial diagnosis, the lower chance you have of developing a recurrence. After year five, there can be recurrences but the farther out you get, your prognosis improves.

Patients are always asking, “Why are we not doing testing?” And the real answer is that there has never been any study that has shown us that finding metastatic disease earlier and intervening is impacting outcomes. That’s a tough conversation when it comes to the radiation exposure and the length of scans that we’d have to do for a subtype of breast cancer like ER-positive breast cancer where recurrences can happen even 7 or 8 years out. This is a question that I get asked about quite often, but we don’t recommend any routine scans after a diagnosis to monitor.

Jean Sachs, MSS, MLSP [00:31:53]

Right. And I’m seeing some comments, we know that some women do recur after that and it’s really shocking. So we need to remember that.

Reshma Mahtani, DO [00:32:06]

I just want to qualify what I said, by saying that it’s not that if you have a symptom. If you have pain or if you have a cough or abdominal pain, absolutely imaging should be done in that situation to investigate what is going on and that should be brought to the attention of your physician.

Additionally, some of us, myself included, do routine blood work every 6 months or so in the first couple years to monitor. Even that’s not technically recommended, but if there are abnormalities in liver function or other tests, that could also be a reason to do imaging.

Jean Sachs, MSS, MLSP [00:32:50]

OK, thank you. I am going to ask this one other question because I think there is some confusion. When should the Oncotype DX test be sent out? At biopsy or when you have your surgery and lymph node?

Reshma Mahtani, DO [00:33:05]

Either is appropriate. There is good, what we call, concordance with a lot of these tests MammaPrint as well as Oncotype, where they’ve looked at the results on the biopsy as well as on the final pathology specimen at the time of mastectomy or lumpectomy.

Sometimes it is sent at the time of biopsy because the surgeon and the medical oncologist are trying to get a sense of whether that individual needs chemotherapy or not. And if they absolutely do, if it may be helpful to give prior to surgery. That information could help guide that decision.

Jean Sachs, MSS, MLSP [00:33:48]

Great. So this is something patients need to talk to their doctor about. Sounds like it could be done either time. OK, I’m going to let you continue. Thank you.

Reshma Mahtani, DO [00:33:59]

Now let’s move on to the metastatic setting. Again, I am focusing on hormone receptor-positive, HER2-negative. I am going to make sure we leave time for questions, and I have inserted some information on HER2-positive disease and triple-negative as well. I want to make sure that this is generally applicable to everybody.

For ER-positive, HER2-negative metastatic breast cancer, typically a hormone therapy — and we’re using that term interchangeably with endocrine therapy, hormonal therapy — with a CDK 4/6 inhibitor. This is what we call a cell cycle inhibitor. These are pills, they’re not chemotherapy, they’re targeted treatments that inhibit the cell cycle and are utilized in conjunction with hormonal therapy. On this slide you see types of hormonal therapy, you see the brand name and the trade name, or the generic name and the brand name, shown for you. Hormonal therapy medications are typically given in conjunction with a CDK 4/6 inhibitor. We have three approved palbociclib, ribociclib, and abemaciclib.

It’s important to remember that every individual’s treatment plan is unique for them. There are certain times where we would consider endocrine therapy alone, but in my practice I generally do start with a CDK 4/6 inhibitor.

Reshma Mahtani, DO [00:35:34]

How is an initial treatment option selected? Of course you and your care team will choose the option that’s right for you, and it may depend on factors like what prior therapy did you get for early-stage breast cancer. Remember we talked about endocrine therapy, chemotherapy, CDK 4/6 inhibitors in high-risk patients, extended adjuvant endocrine therapy in the early-stage setting, meaning beyond 5 years, taking a longer duration. All of those things factor in. Whether you’re pre- or postmenopausal can impact your choice of therapy. What side effects you are willing to tolerate, what side effects you may have as a residual from your prior treatment, your other medical illnesses and other medicines that you may be on.

Now again, the focus is on testing for this presentation. When we use the term biomarkers, we’re talking about tests that can be done on the tumor. Biomarkers are certain proteins, genes, or changes in the genes — we call these gene mutations — that can happen in cancer cells. And this type of testing is useful to show which treatment is most likely to work for your cancer. Some cancer drugs are only effective for people with certain cancer biomarkers. I’m going to bring up the example of triple-negative breast cancer here. A stage IV, or metastatic, triple-negative breast cancer patient who’s newly diagnosed this biomarker, PD-L1, is an important one to identify a patient who may be eligible to receive immunotherapy in combination with chemotherapy as the first treatment for stage IV triple-negative breast cancer.

We talked about germline genetic testing, BRCA1 and 2, for early-stage disease. I made the comment earlier, I will make it again now. If you did not undergo germline genetic testing as part of early-stage testing, if you develop metastatic disease or you present with metastatic disease — we call that stage IV de novo metastatic breast cancer — you absolutely should have germline genetic testing. There are two oral therapies called PARP inhibitors that are available treatment options, and there are other genes that can be mutated that we’ll go through including this gene PIC3CA. And this information can impact the availability of immunotherapy as a treatment option.

I showed you that slide when we were talking about HER2 in the early-stage setting, and now I want to bring up this concept of HER2-low. And there’s even now HER2-ultralow, which is a more recent designation.

In the early-stage setting, this information hasn’t factored in yet, but I do think it will in the future. In the metastatic setting, HER2-low has absolutely factored into treatment options because some of these tumors now are eligible to take drugs that used to be only for HER2-positive, 3+ or 2+ with what we call gene amplification. Now if your tumor is HER2-low, either 1+ or 2+ without gene amplification, those are called HER2-low tumors and there’s an opportunity to take a drug that was previously only approved for HER2-positive breast cancer if you have HER2-low disease. We’ll talk about that in a little bit more detail.

Let’s talk about reasons that hormonal therapy stops working, and that could be hormonal therapy with a CDK 4/6 inhibitor or hormonal therapy alone. We know that in the presence of our therapies these mutations can develop and they can cause resistance to the drugs that we’re giving.

Reshma Mahtani, DO [00:39:57]

Resistance is when the current medication stops working and the cancer can continue to grow despite someone being completely compliant, taking the medication as prescribed. At that point, testing for actionable mutations may help your doctor recommend targeted treatment options. For example, we talked about CDK 4/6 inhibitors and endocrine therapy being the initial treatment. Several trials have investigated this as the first line treatment, and there are studies that show that taking these drugs upfront is associated with an overall survival benefit. There are also studies that have started to look at, if the first treatment stops working, could we switch to another CDK inhibitor or switch to a different hormonal medication and continue this class of CDK 4/6 inhibitors. We think of doing this especially in people who’ve had really long durations of disease control on CDK 4/6 inhibitors. So this is an option that can sometimes be available.

For individuals who have exhausted all of our targeted treatment approaches, including CDK 4/6 inhibitors and some of the other molecularly-directed targeted treatments and endocrine therapy that I’ll be talking to you about, antibody-drug conjugates are now a type of therapy that are available. It’s a very targeted delivery of chemotherapy via an antibody. This is called a Trojan horse. The chemotherapy is directed specifically to a target on the surface of the cancer cell, and the chemotherapy is directly delivered there.

Trastuzumab deruxtecan [Enhertu] is one such antibody-drug conjugate. This is approved for HER2-positive breast cancer as well as HER2-low. Sacituzumab govitecan [Trodelvy], this is approved for triple-negative breast cancer as well as hormone receptor-positive, HER2-zero as well as HER2-low breast cancer. And trastuzumab emtansine [Kadcyla] is for HER2-positive breast cancer.

I just want to show you this common mechanism of action. Don’t get intimidated by this slide, I’m going to talk you through it, it’s actually pretty easy. You see the tumor cell here, and you see the antibody-drug conjugate coming with the targeted chemotherapy payload, attaching to the target, getting internalized into the cell, and then the chemotherapy falls off and in certain cases drifts across the cell membrane and kills off neighboring cells that have some of that same target expression. This is the mechanism that we call the bystander effect, and this is why, for example, drugs like trastuzumab deruxtecan can work in HER2-low disease.

Finally, let’s talk a little bit about molecularly-directed targeted therapies that are designed to target specific genetic or molecular alterations in cancer cells. Olaparib [Lynparza] on the bottom, there’s another one also called talazoparib [Talzenna], is in that class of treatment called PARP inhibitors that are available if you have a germline BRCA1 or 2 mutation. And then there are other drugs, you see the trade name and the generic name, that are based on other mutations that I’ll show to you here.

One mutation that is tested for, typically in a liquid biopsy, so this is where liquid biopsies in metastatic disease have saved a lot of women the trouble of having to go through multiple tumor biopsies. This is a blood test that can look for the presence of this mutation in the estrogen receptor. It’s called the ESR1 mutation. If that mutation is found, you could potentially be a candidate for this drug called elacestrant [Orserdu].

Another test that can be done in a liquid biopsy, can also sometimes be done on a tissue biopsy, is for this pathway alteration in this pathway called the AKT pathway. It includes AKT, PTEN alterations or the PIK3CA gene. It could mean that these drugs, alpelisib [Piqray] or capivasertib [Truqap], which target these specific mutations, given in combination with fulvestrant may be your next best treatment options.

I mentioned the BRCA mutation. This is still considered biomarker testing. It’s germline genetic testing. It can also be tested for on the tumor. We call that somatic BRCA mutation testing. If you do have this mutation found in your tumor, you should go back and still have germline genetic testing as well. And olaparib or the other PARP inhibitor that’s not shown on this slide, talazoparib, are approved therapy options.

Reshma Mahtani, DO [00:45:13]

When is biomarker testing needed alongside your journey for your decisions? More and more we’re thinking of doing this even at first-line diagnosis because there are newer drugs that are coming, including PIK3CA inhibitors that are showing a benefit upfront in patients that have very aggressive disease that recur within 12 months of completing early-stage treatment. Knowing if you have that mutation upfront may soon be very important.

Typically nowadays we’re testing after first line treatment, and we’re looking for actionable mutations. The key is that this type of testing can be done repetitively because certain mutations can emerge in the presence of our treatments. These are discussions that your medical oncologist should have with you.

Here you see genomic testing during the breast cancer timeline. I’ve tried to include this as a big picture, early-stage and metastatic continuum for testing.

Remember in the early-stage setting we call our treatments adjunctive treatments or additional treatments. So adjuvant therapy for the presence of germline mutations for ER, PR, HER2; assays that can help make the decision about whether you need chemo or chemo and endocrine therapy or endocrine therapy alone.

At the time of first metastasis, it’s always important to confirm that you’re dealing with breast cancer and not another type of cancer or not something that’s completely benign and just looks suspicious on imaging. Confirm that it is cancer. Confirm that ER, PR, and HER2 are the same, they can change. If you haven’t had germline testing in the early-stage setting, it should be done in the metastatic setting. PD-L1 testing is important to understand whether or not immunotherapy would be added to chemo for triple-negative breast cancer. These other mutations that I’ve talked about, PIK3CA, ESR1, AKT mutations, HER2 mutations. Things that I didn’t get a chance to talk to you about, but all of this information can be seen on a liquid biopsy. In certain instances, tissue biopsies are needed as well, but we’ve made a lot of progress in treating breast cancer.

I will end with two slides that just kind of are a step back, big picture view. This is a quote from a physician who was asked to chair the European Society of Medical Oncology personalized medicine task force. And he said, “Personalized medicine comes from the results of research efforts over the past 20 to 30 years to understand the complexity of cancer. Not only between different tumor types and organs, but also within any tumor, there is enormous heterogeneity. As a result, an approach of providing the same kind of therapy to the same patients just because their tumors arise in the same organ — breast, lung, prostate, or whatever — will be effective in general, but does not work for everyone unfortunately.”

Our goal is to offer personalized medicine that can be described as the right medicine for the right patient at the right time.

And with that, I will take any questions.

Jean Sachs, MSS, MLSP [00:48:55]

Thank you so much, Dr. Mahtani. You covered a lot, and I said this last week too, it’s very complicated. We understand that as a patient you have a lot of information to digest, so it’s so important to have a medical oncologist, like Dr. Mahtani, who will sit with you and help you understand.

I want to just ask a general question. With all these advances in testing, are insurance companies keeping pace? Are they being paid for? What do patients need to know?

Reshma Mahtani, DO [00:45:29]

Those are great questions, and I think that in the situation where we have approved therapies that are on the basis of certain mutations, I’ve not had a lot of pushback.

I have had some insurance companies ask for proof of that mutation. When you order the test, they’re looking through your medical records to make sure that you have a liquid biopsy or a pathology report, something that confirms that that mutation or protein alteration is present, which guides their coverage of your medication.

Jean Sachs, MSS, MLSP [00:50:08]

Right. As patients you’ve got to ask the questions and be advocates so you don’t get surprised if you’re going to be charged.

One test you didn’t talk about is the PET-FES test, and I don’t know if that’s something you’re comfortable sharing a little bit about.

Reshma Mahtani, DO [00:50:25]

Yeah, I think that’s a great question. There is a new type of PET scan, it’s called a Cerianna PET or an FES, an estrogen-labeled PET scan that uses a different radioisotope and it focuses on cancer cells that are expressing the estrogen receptor.

This is a test that is being utilized more and more in cancers that are of lobular subtypes, where they don’t show up as well on imaging. I have started to order these FES-PETs, especially in those cases. Some insurance pushback sometimes, and a little bit more coordination in getting the test because it’s not as easily available. But it is something that has been particularly useful in my practice for lobular breast cancers.

Jean Sachs, MSS, MLSP [00:51:18]

That’s great. Living Beyond Breast Cancer did just update content on this, and we also have a blog. We’re so short on time, but I do want to ask, there is a little bit of confusion from our metastatic patients that are listening and our early stage. Does MammaPrint or Oncotype apply to anyone in the metastatic setting?

Reshma Mahtani, DO [00:51:39]

Right now we’re not utilizing MammaPrint or Oncotype for decisions in the metastatic setting. Those are tests that are done on the tumor to help us predict what the risk of recurrence and what the benefit of taking chemotherapy is. In the metastatic setting it wouldn’t be indicated.

Although there is a test that is accompanying the MammaPrint test, it’s called BluePrint. It can sometimes be helpful. In the early-stage setting, there is some investigation to look to see if that sort of grouping of breast cancers in the metastatic setting may help make decisions, but it’s not a routinely offered test in the metastatic setting.

Jean Sachs, MSS, MLSP [00:52:21]

Great. And Living Beyond Breast Cancer does have information on BluePrint also if you look on our website.

I think we’re going to have to end. I want to tell everyone the session last week with Dr. Teplinsky focused more on treatments and side effects. Dr. Mahtani touched on some of them, but if you still have questions about the role of ADCs or CDK 4/6 inhibitors, please make time to watch that. I think it’ll be really helpful.

If you are seeing a general oncologist that doesn’t necessarily specialize in breast cancer, since LBBC serves people all over the country, what do you suggest they do to make sure they’re getting the best care possible?

Reshma Mahtani, DO [00:53:10]

You bring up a very important point, and fortunately a lot of even community oncologists who treat multiple tumor types are now specializing within their groups. And there may be one person that does more breast cancer. As we know, breast cancer is one of the most common subtypes of cancers that medical oncologists see. It’s rare to find someone who has no breast cancer patients in their practice, which is reassuring.

But, to your point, being your own advocate and making sure that you’re coming armed with a list of questions. I love it when my patients come in, they’re always apologizing to me and I say, please don’t apologize. This is why I love taking care of breast cancer patients. They’re so engaged, and they ask me great questions. You should feel empowered to ask your oncologist questions. And if you’re getting a lot of pushback, that may be a sign that it might be time to get another opinion.

Jean Sachs, MSS, MLSP [00:54:15]

That’s great advice.

Session 4 | Practical matters: The financial and time toxicity of breast cancer

Kelly Choy-Wilson [00:00]

My name is Kelly Choy-Wilson, and I am a young advocate of Living Beyond Breast Cancer’s patient advocate training program. I will be acting as your moderator for today’s program.

In 2021, at the age of 42, I was diagnosed with stage I, triple-negative breast cancer. Being diagnosed with cancer was shocking and led to many challenges. Facing those challenges head-on, I have gained confidence, strength, and learned a lot about myself. Today, I am healthy and thriving.

We all know that the impact of a breast cancer diagnosis reaches beyond treatment, and today we are going to discuss another side effect, the financial and time toxicity of breast cancer.

After being diagnosed with breast cancer in 2021, I went on short-term disability right away. Unfortunately, because I had already used 1 1/2 months of short-term disability for another condition earlier in the year, I didn’t have the full 6 months of short-term disability, which would have covered my salary until I was able to apply for and receive long-term disability. This left me with 1 1/2 months without pay, as if I didn’t already have a lot to deal with. I reached out to my cancer center social worker, and she was able to provide me with grants that I could apply to for assistance. One of the grants that I applied to and received was the LBBC one-time grant, which led to my current advocacy. Thank you, LBBC.

I’m sure that like myself, many of you have faced similar financial challenges.

I am honored to introduce you to today’s speakers, Erin Bradshaw, executive vice president for the advancement of patient services and navigation at the Patient Advocate Foundation, and Dr. Pallav Mehta, a medical oncologist, hematologist, medical director of Reimagined Care and assistant professor of medicine at MD Anderson Cancer Center at Cooper.

To learn more about both of our exceptional speakers, please go to lbbc.org to read their full bios. We are going to hear from Dr. Mehta, who will discuss financial and time toxicity from a clinical perspective, and then from Erin, who will share some scenarios and provide strategies and resources. Welcome Dr. Mehta.

Pallav Mehta, MD [02:37]

Thank you, Kelly. Thanks for sharing your story and for shedding light on this really important topic that we’ll talk about.

I have been an oncologist for 20 years, so I thought it would be helpful to look back and say: How has this issue changed? What is the evolution of financial toxicity in cancer? I actually remember distinctly the first patient I treated with breast cancer. It was in 2004, and I did my training at the Fox Chase Cancer Center here in Philadelphia. It was a woman who lived in North Philadelphia. And I remember her saying that coming back and forth, the parking was a real problem, just the cost of the parking.

At the time, it didn’t really register as to why, when you think about the cost of treatment, this might actually be an issue. But over the years, I’ve come to realize, and the medical community in oncology has come to realize the importance of this term, financial toxicity. It actually wasn’t even a word in our literature until about 2009, 2010, when we started to focus on it more. Today, almost every cancer center has some policy, personnel, and some process around financial toxicity.

In 2004, what was happening in cancer?

When you look at the treatments of cancer back then, 20 years ago, particularly in breast cancer, most of the treatments were chemotherapy. We didn’t really have targeted therapies. We certainly didn’t have very many oral medications. The only oral medications back then were the hormonal agents, the estrogen blockers. And metastatic breast cancer, unfortunately at the time, really was limited in the types of options we had for patients, and the life expectancy was limited. Patients were on treatment for much shorter periods of time.

Even the patients that were cured from their treatment often didn’t receive months and months, and certainly not years and years of treatment other than these hormonal agents. Even the supportive drugs that we had — the medicines that we use currently for prevention of nausea, prevention of diarrhea, keeping our blood counts stable during treatment — we didn’t really have too many of those. And if we did, our guidelines at the time told us not to use them unless there was a problem. So we didn’t really use things preventatively at the time.

Genomics, which is its own conversation, but the whole field of genomics — all the testing we do for the different nuances of the breast cancer and the different targets we look for —didn’t even exist as a field 20 years ago. And even genetics, which is when we look at a patient’s genes trying to determine if the cancer is hereditary, even that testing was very limited. The only genes we actually knew about were the BRCA 1 and 2 genes at the time. Today we have dozens and dozens of genes and more to come.

I think one of the most significant issues though is this out-of-pocket cost. In 2004, there was actually a change in the tax code that incentivized employers to start offering what was at the time called these high-deductible health plans. For those who had health insurance at the time, you remember that the maximum out-of-pocket with most of the previous plans used to be somewhere around $500, maybe as high as a thousand dollars. The high deductible plan, the idea of course, was the deductibles went up, so the premiums went down. And the idea was to then potentially cover more people and allow “consumers,” which really is another name that an insurance company would give a patient, to be more involved in their choices.

Pallav Mehta, MD [06:59]

The problem with that, of course, is that when it comes to certain things, the involvement a patient can have in choosing, it could be limited. If you’re having a knee surgery, there may not be an urgency to that. You have time to think about all the different doctors you could see and the different places you could go. But when you have a breast cancer diagnosis, that time is more limited in finding who you want, to get the treatment started.

The other sort of big change has been where cancer is treated. Most cancer at the time was treated in what we call community practices, which for most patients could be just a few miles down the road. And there were hundreds if not thousands of these community practices made up of a few physicians, a few oncologists, sometimes two or three, sometimes 10 or 15. But a lot of these small practices thrived in the community. And the bigger academic centers were where about 25% of patients were treated, those were used more for second opinions and then the patients would go back to the community.

Oncologists themselves just didn’t think about this at all. It wasn’t part of our conversations, it wasn’t part of our literature. But flash forward 20 years later, now we think about all the therapies in breast cancer — and breast cancer really does lead the way — which is great, but all those therapies are costly. Targeted therapies, immunotherapies, biologic therapies. And our metastatic patients now, thankfully because of our success, are living much longer and many of them even in in a chronic disease type of situation.

So you have more people getting treatment and more people getting longer and longer treatments and staying on treatment. And those oral agents, anyone who’s been on a targeted oral agent for breast cancer knows that the cost of those is astronomical. Somewhere in the $15,000 to $30,000 a month range for medication that may be one or two tablets a day.

The supportive drugs, again, this has been a great advance in all cancer, particularly in breast cancer. The days of women vomiting in the chairs, we really don’t see any of that anymore because our nausea meds are tremendous. Our ability to keep immune systems healthy has been tremendous. Again, at a cost. Genomics, we test patients’ cancers for all sorts of things now to decide on treatments. And then, as I said, those high-deductible health plans, the majority of patients now are on high-deductible health plans.

And a lot more cancer as those community practices — which I initially started my career in a community practice, currently I’m at an academic medical center — but all those community practices either shut down or due to various changes in reimbursement, were bought by larger systems, which has changed the fee structures. Hospital-based systems have different cost structures, have different needs, they have larger personnel, they have more services, and so there are different fees associated for patients. Not to mention that these are usually not right around the corner for most people. You’re talking about transportation and driving long distances and parking, and it is just a much more involved treatment during that day.

As oncologists, thankfully, we are now aware of the problem. I make it a point in most patients that I see that at the end of our visit, I always ask them, “How’s it going with the costs? Are we okay with co-pays?” And if not, I make sure they’re connected to the right people on my team.

What can you do about all this?

Erin, I know, will get into much more detail about this, but as an oncologist, what do I think about and what do I think a patient can do.

I think, understanding the costs. Now that sounds easy, obviously it’s quite complicated. I feel like most of us need a degree just to understand what insurance covers. I remember I had an MRI of my knee last year that was covered and authorized, except it was over a thousand dollars, which I didn’t realize that “covered” is not always covered. But understand if your cancer center has a financial counselor, because now many, if not most, have somebody whose responsibility it is to communicate with patients to talk about the cost — ideally, before you ever start. If you’re about to start a regimen, a one-year regimen of chemotherapy, Herceptin, and an oral medicine, you want to know before you start what sort of costs, not just the cost of treatment, but the cost to you that you’re looking at, so you can budget appropriately.

Financial assistance programs are available. A lot of this money does not get used. There are nonprofits that clearly are helping. Pharmaceutical companies have programs. Hospitals and cancer centers have programs, particularly the larger academic centers have programs.

Don’t forget about crowdfunding. It’s a newer way to raise money, but it is something that has been successful for a lot of people. When you think about friends and family and even strangers, when someone has cancer, we want to help and sometimes all we know to do is bring over lasagna. But you’d be surprised how people really need, you can band together a hundred or a thousand people, how the community can really support a patient undergoing treatment.

Maximize prescription savings. There’s these online comparison tools out there. GoodRx is one of them. Using generics. And take advantage of virtual and on-demand care. This is something that I, personally, am very interested in. I’m the medical director of a startup company called Reimagine Care, which looks at virtual and human-based extension of cancer centers. There’s different uses of telehealth and texting technology and even in-home care that can be done in various parts of the country to make it easier for you.

The bottom line is speak to the providers because I think if there really is one thing that’s changed, it’s that we want to hear from patients. If patient doesn’t tell me, I won’t know that they’re having an issue. But I’ll hear from somebody else that they may have been looking at declaring bankruptcy.

When really look at the options of treatment, you would be very surprised at how, as oncologists, we sometimes favor one treatment or another. Not necessarily because it’s better, but just because we’re used to it and because we’ve been giving it for years. But for certain patients that one treatment versus another equivalent treatment could be thousands if not more than that, less for them.

So have that conversation. Have the conversation with your nurse, your nurse practitioner, your oncologist. Think about treatments, think about the frequency of visits. They may want to see you every week, but ask them if that’s really necessary. Again, you’d be surprised, it may not always be necessary to see a physician every time, because each of those visits has its own co-pay. Think about imaging tests. Do you really need a CAT scan every couple of months? But these are things you want to have conversations about. Be ready to have those early on and set that stage with the providers so that your expectations and their expectations are appropriately aligned.

So I’ll stop there and hand it to Erin.

Erin Bradshaw [15:21]

We know that navigating the cost of care, as was just presented, is something that many people face at all different types of where they are in their journey and their diagnosis. And the term financial toxicity really describes for us the practical and the emotional impact of the cost of care on individuals and family while they’re managing their breast cancer diagnosis.

During this session I want to share a little bit more about Patient Advocate Foundation, some of the areas of support that we offer as well as use some examples to demonstrate scenarios that you might find yourself in or might see yourself in the future as we talk about the medical cost as well as the insurance navigation.

Patient Advocate Foundation is a national nonprofit charity, and we provide case management and financial aid to patients with different types of life-altering or chronic disease. We were founded in 1996 based on an individual who had experienced some challenges when navigating their own breast cancer journey. We have helped 2.5 million patients since our inception and we are there to provide support around administrative barriers that often present after diagnosis. And as you can see, we’ve provided a lot of direct financial support, but in particular within case management our role is more of an intervention arm about helping people navigate to the best resources. And with our support last year we did about $18 million in debt relief on behalf of patients.

Five out of the 10 issues that people call us about are around the disability, health insurance, and out-of-pocket medical costs. I see in the chat and some of the questions that this is arising, and I’m sure we’ll have some time to speak about that towards the end.

We recently conducted a survey, which I thought was very powerful and really clearly demonstrates the burden of administrative task to individuals that are navigating the system. I wanted to set the stage with this because it describes the ever-heightened need for resources like Patient Advocate Foundation, as well as others that were mentioned prior, through other navigators, social workers, counselors within the hospital, to help get through a lot of the complexities and often uncertainty around safety net resources or financial solutions that might be there to support you as you navigate your treatment.

Case management is a one-on-one intervention. I want to spend a brief moment just talking about it. It is the heart of why we were founded. It’s helping you get services through the ecosystem of all safety nets available.

You’ll notice three major buckets. You got health insurance navigation, helping you determine what benefits you should pick from. And you’re going to notice a bit of a theme between both of us presenting around some of the common areas that we really want to focus on. There has been a lot of evolution around health insurance design. There also might be some changes in your healthcare needs, that maybe the plan that you are currently on may not meet your current needs moving forward.

I highly encourage and I want to just put a plug right now, it is open enrollment for Medicare and will be marketplace. Also keep in mind, with all your employment open enrollments. Always assess and look at what plan options you have available to you. Screen against all of those. What kind of treatment you’re on or you might be projected on. Determining from medication to providers to networks, it’s always a great idea to look at the overall cost between your premium as well as your out-of-pocket costs. All of those core competencies are what we help provide help with in case management.

But also, if you are running into a situation with your insurance, with denials or appeals or maybe there’s a coding error or you just don’t quite understand why something’s not being covered, those are areas that we can provide aid to. As well as disability navigation. If you are looking at screening yourself against that, you’re an abled body moving into a disabled body and wanting to know what kind of benefits you potentially are eligible for. Help with application, help with the appeal process if you find yourself there. As well as all the support for financial hardships in exploring external resources to reduce those medical costs and everyday expenses and even helping with those applications.

Erin Bradshaw [20:13]

I’m going to focus on when insurance arises and then how to manage medical debt from a very high level, and then answer some questions after.

We know that as you navigate through your healthcare journey, there are lots of roadblocks that might present. Insurance, as I mentioned before, some of those unknown circumstances of out-of-pocket costs. And you might find yourself in a situation where you’re going to the pharmacy and maybe going to pick up a medication and really didn’t have any transparency around that cost. You might find yourself in a position to utilize funding that was saved for maybe a mortgage or a utility to get that medication or you might walk away, and we don’t want that to happen. We want to make sure that we really explore all possible solutions so that you have the treatment that you’ve been prescribed and that you’re able to move forward with your care journey.

Employment protections and workplace entitlements are an area that we want to pay a lot of attention to. You might not be familiar with everything that you have available to you. Do you have short-term or long-term benefits? Are there any auxiliary benefits support, or discounts, through your health insurance through your employer? We support you in those areas as well as some of the protections in place to keep you from losing your job, like family medical leave. Or if you are moving into an opportunity where you might have to transition out of the health insurance that you have, you want to be sure that you understand what they are so that you can best utilize those resources should you find out that you might have to transition into a disability state or maybe not be able to work for some time. You don’t want to lose any valuable benefits.

We all know that as you navigate the journey of your care, that the cost of living really can be very impacted. Because if you find yourself in a reduction in income or with the large out-of-pocket expenses that were unexpected, they really do cause a challenge. And so those are often resources that you’re not familiar with and would benefit from someone supporting you and navigating you and asking the right questions to connect you.

Let’s start with basic terminology in this topic of navigating insurance. In this case example that I’m going to be talking about, we’re going to be talking about someone who has run into an insurance denial. There are really different levels of appeal types and prior authorization: Denials before services are rendered. Post-treatment, denial for a payment of care that you’ve already received. Then there’s urgent or expedited appeals. So there are opportunities where you can request an urgent overturn, and that often is supported by a provider and medical evidence to quantify the need of a quick turnaround.

I want to pause for a minute: You can see there’s a lot of timelines associated with it, and sometimes they’re not that quick. But it’s also very critical to stay within the timeline so you don’t lose out on the opportunity to contest a particular denial. Oftentimes your provider is a huge advocate for you. We at the organization also provide some administrative support and gathering and putting those things together for you too through all different levels of appeal.

For the purposes of this conversation, I’m going to use Sandra. She is a 64-year-old female, lives in a suburban area with her husband and two dogs. Her children are grown but live nearby and are frequent visitors. She was diagnosed with triple-negative breast cancer, also has diabetes, and has completed her chemotherapy and a mastectomy. She works as a contractor so that means she doesn’t have benefits through employer, but she was covering herself through an individual PPO that she purchased through the Healthcare Marketplace.

Some of you might be familiar with hearing the Affordable Care Act. You hear the term Obamacare. This is an opportunity for people to purchase insurance when they don’t have other benefits available to them, through their state. Now that she’s recovered from mastectomy, Sandra’s oncologist has wanted to try a new chemotherapy regimen, and the insurance plan has denied the coverage of this treatment, citing that they’re classifying it as experimental or investigational for her cancer type.

In this case we would want to understand what is the reason for denial and then look at her insurance plan’s appeal process. They might have an internal process. There should be a letter or something that gives us some summary on how to appeal and some timelines. We would want to work with the healthcare team and gather information, like get a letter of support from the healthcare team including reasons of medical necessity, obtaining any supporting medical charts, testing, or notes. And obviously staying organized and paying attention. All of this can be very overwhelming and also can be difficult to keep track of, so it’s helpful if you have someone who’s close to you that wants to support that or there’s an advocate or even a hospital support system. The goal here is to be very factual to come up with contesting reasons and hopefully overturn this scenario.

Erin Bradshaw [25:32]

In this case we were suggesting a peer-to-peer, which involves a discussion between the prescribing physician and the medical director at the insurance company. This is a steppingstone before you actually get to a formal appeal. And the provider can share things like medical or treatment history or details about the condition. Medical directors can use their own judgment and overturn this denial at this stage so that the patient can pursue that treatment.

This is often coordinated between the provider and the insurance company through a scheduled call. And this is probably often done without you necessarily knowing that’s happening because your providers are there to try to really get to the treatment that you need the most proficient way.

For another angle, I’m going to talk about common terms. Insurance is very complex, as mentioned before. Not only do you have a premium, that you’re paying each month for your benefit, you have a deductible. And a deductible is the amount of out-of-pocket cost that you’re responsible for before your insurance begins to pick up some additional cost. You’ll hear some variables like co-insurance, which can be a percent of a particular treatment or procedure, or a co-pay, which is a set amount, so maybe $20 to see a specialist or $50 for a particular medication. And then there’s an out-of-pocket maximum, which is where the plan has required the patient to pay up to a certain amount. And then after that is met, they should be paying 100% of in-network and covered benefits.

As you explore your insurance options, you want to look at the overall cost of the year. What is your premium? And then there’s a mathematical equation that could be helpful in making sure that you’re getting not only the benefits that best suit your needs but also which one might make the most fiscal sense. And that is really a personal choice. I will share that there are great resources by Triage Cancer that have these worksheets that you can actually fill in to look at that comparison as you’re looking at these types of decision making factors.

The other thing is you want to make sure that your plan is paying in accordance. The explanation of benefits and those things are good to map against what you understand your benefit plan should be paying and making sure that there hasn’t been some oversight or lack of insurance submission so that you’re not paying more than you should.

Mara is a 37-year-old, lives with her husband in the city. She’s got stage II ductal carcinoma, and she works as a graphic design artist for a large nonprofit and has a high-deductible health plan through her employer. The cost of the oral chemotherapy along with the medical expenses she’s incurred from all the testing as well as lumpectomy have become a substantial financial strain on her and her family.

What we would want to do is look at any charitable co-pay program that might exist to help cover some of those out-of-pocket costs for her treatments that she’s having and screen her and see if there’s eligibility for co-pay, co-insurance deductibles, and sometimes premiums. There may be a manufacturer co-pay card as well. So we’d want to look at the medication she’s been prescribed and see if they have a co-pay card or discount card that she could apply towards her insurance to reduce that out-of-pocket cost, to make it more affordable. Sometimes they can be as low as $5 a month.

The other thing is — this is very much mirroring what was shared before, but I think it’s great advice — is discuss with your doctor. They’re very aware of how expensive treatments can be today. They also want to make sure that you’re getting access to the treatment you’re being prescribed. There might be some negotiating on a bill that you can’t afford, whether a payment plan or discount through the facility or the provider’s office themselves. They might have their own charitable program, be able to map you to an asset within the hospital or provider to screen you against any available financial assistance, as well as if you have a health savings account. In her case, she has a high-deductible plan. So has she contributed to the health savings account, which is that you can take pretax dollars and apply to pay some medical expenses and cover that deductible and out-of-pocket cost. Sometimes if you’re insured by an employer, they might also be contributing into that. And you want to make sure you’re utilizing every valuable resource that you have. And then of course, always have to say, review your plan options every open enrollment and ensure that you have the best plan that suits your current treatment needs.

Erin Bradshaw [30:09]

I just want to call out a resource that you may or may not have heard of. It’s called Dollar For. This helps patients navigate hospital financial assistance or charity care. It is very specific to hospitals that have received federal funding, and there’s a pre-screening tool. You can go online dollarfor.org. It doesn’t help with any other medical things, like appeals and negotiation, but it does very seamlessly connect you to any financial assistance that you might be eligible for through the hospitals that receive federal funding.

I just want to call out, we have an educational resource library, education@patientadvocate.org. Very robust. We have a national financial resource directory that you can go to and put in some specifics about yourself, and it will give you an opportunity to explore vetted resources that we have been adding for years around whether it’s disease specific, state specific, topic specific. We also have some educational materials around how to appeal the disability process, medical bill management, and more.

These are our websites [on screen]. Patientadvocate.org will actually connect you to all of these resources. Our case management services I spoke about earlier, we do have a co-pay relief program to help with some co-pay costs. We have some financial aid funds: There’s a scholarship for individuals with disease that has impacted their education journey. There’s our national resource and resource library.

In closing, I’ll just share one of our testimonials that were recently received, and I think this will resonate to the topic that we’re speaking about.

This is Kimberly. She has breast cancer, and she came to the organization because she had $24,000 in outstanding costs and could not understand how it was not being covered by the insurance. Her case manager worked with the hospital and insurance to try to figure out why there were so many bills, and there ended up being some incorrectly filed bills that were not able to be solved very seamlessly. Our case manager stepped in and took over this burden for her and put together a plan and got this all coordinated, which ultimately ended up with it being paid in accordance. Which was super supportive to Kimberly specifically.

But I think the biggest thing I want to mention here is that if you notice these things, it’s really important to say something very soon because there are timelines associated to rectifying any kind of insurance and billing scenario, and we wouldn’t want to miss that timeline when there are mistakes that can happen.

Kelly Choy-Wilson [32:50]

Thank you, Erin and Dr. Mehta. I just want to encourage everyone if you have any questions to enter them in the Q&A. And it does look like some more are coming in.

I wanted to start with a question for Dr. Mehta based on my personal experience and seeing some of the comments in the chat.

It’s very stressful to get a cancer diagnosis, go through treatment, and then also deal with financial issues. What do you recommend to your patients when they are mentally exhausted or stressed from dealing with these type of issues?

Pallav Mehta, MD [33:29]

Yeah, it’s an important question. It’s something that, as an oncologist, because we’re just more aware of this issue now and because communication has gotten a lot better between patients and the oncology team and the additional staff we have on the oncology team, the awareness alone allows us to always have in the back of our mind about this potential problem. I’m not alone in saying that asking patients about cost and how it’s going is a part of our routine for a lot of us. When you do that, I think it validates this issue because what I used to see was patients would feel guilty even mentioning the cost issue to me. I think that was partly because you feel like you’re fighting for your life and so God forbid you would mention anything about the cost.

But again, that communication and having direct communication from day one with not just the oncologist but the other team members, and knowing who those team members are that can help you, is really important.

Kelly Choy-Wilson [34:46]

Thank you. We have another question for someone who is stage IV, wondering what other resources besides Social Security disability they have, because they haven’t worked enough to be qualified.

Erin Bradshaw [35:04]

I can speak to that.

Social Security disability actually has three options. You have SSDI [Social Security Disability Insurance], which is relative to work credits and quarters that you’ve paid into, which sounds in this case, she has not worked enough. There’s Supplemental Security Income, which would be dependent on income and asset in the household. Sometimes people fall into that, but it’s had to say not knowing specifically this individual’s background, if they happen to have a household income from whether a spouse that might disqualify them. And then the other option would be from retirement standpoint.

Depending on the state of the individual and where they live, some states have some short-term-type disability. And then if they had worked. But outside that it would be probably mapping to potential resources and that would require us to probably work very specifically with that person to understand their location and where they are financially to give them a really well-rounded answer. That is one of the challenges with disability is that it does have some very specific guidelines associated to it.

Kelly Choy-Wilson [36:22]

OK. And I do see another question that mentioned national resources versus state by state. So would your organization be able to help people navigate what’s federal versus state-to-state issues?

Erin Bradshaw [36:38]

We would, and also, you have such great assets from a local standpoint, from your community action agencies as well as your social workers at your location. We can do the same thing, but some of those can be usually more top of mind if they’re in your community. But certainly that’s what we do

Kelly Choy-Wilson [37:00]

Is it possible to apply for SSDI while still working but anticipating that you might need it.

Erin Bradshaw [37:08]

The way that Social Security defines themselves is that you’re not able to work or your condition is going to exceed 12 months. So there’s a 12-month break, and you can’t apply when you’re working, unfortunately. It’s kind of a catch-22 because obviously you need some income for that time.

If you have employment benefits, that would be ideal, maybe you can have some short-term or even long-term benefits. The application for Social Security disability does take a little bit of a time and there might be a gap where you’re waiting for decisions. I saw another question there about how do you decide, and I think that’s such an individual conversation and I think a provider can be a really good support system for that too, because of the guidelines around disability themselves. They want that you’re unable and won’t be able to work 12 months plus. There are some compassionate allowance conditions or things that are considered escalated due to the stage or type of disease that can fast-track some of the decision making.

Kelly Choy-Wilson [38:25]

Can you talk a little bit about time toxicity and how to address that?

Pallav Mehta, MD [38:32]

Yeah. As I mentioned financial toxicity started to enter the literature of oncology about maybe about 15 years ago or so, time toxicity is a newer idea around what patients are going through. Financial toxicity and time toxicity to some extent overlap because it’s all the time that patients are spending on their cancer. Obviously that includes the treatment itself, which may not be able to change, of course, because you need treatments and they have to be over a certain period of time and certain frequency. But other things, just the drive, how far away is the cancer center, the transportation, the walking to the place, the labs, the imaging tests. And then all those calls, when you’re on the phone and you’re dealing with insurance companies, you’re dealing with the schedulers at the cancer center and at the surgical place. I’ve had patients tell me that the day before they were on the phone for 3 to 4 hours trying to deal with one issue. This is something that we are starting to recognize in the oncology community. So both in my role as a breast oncologist, but also in my role at Reimagine Care, it’s something that we’re talking a lot about and trying to understand the specific issues around it and where we can intervene. I think one particular place to intervene — I’ll mention one from the oncology side of things — is when you have those conversations with your oncologist, there may be options that are not as frequent. For example, I had a patient for whom I had recommended a treatment where she had to show up 12 times, so once a week for 12 weeks for a treatment, but she just couldn’t. She had a young son who was on the spectrum and she had to take care of him and it was just too much. And so we just changed it to four doses instead of 12, just as good. But had she not told me, I would never have known.

On the Reimagine Care side, this is where I think virtual, on-demand care online comes in. Use online access, a lot of centers have good access for appointments. Don’t get on the phone for those if you don’t need to. Understand, even insurance companies and how their online portals work and processes work. You can save yourself a lot of time just understanding some of the technology and those options that are available.

Kelly Choy-Wilson [41:17]

Can you speak to us about Reimagine Care? Tell us a little bit more about it.

Pallav Mehta, MD [41:22]

Yeah, so Reimagine Care is a venture capital-funded startup company, founded about 3 years ago to address the needs of patients on treatment. We recognized that patients on treatment, when they’re in the cancer center, they’re taken care of. They have their nurses and the doctors and the team is kind of enveloping them in the care, but once they leave the cancer center, the ability to get back in touch and the ability to just get questions answered and symptoms dealt with, all of that suddenly kind of reverts back to what we used to do 50 years ago. We address that with a virtual but also human — we have nurses and nurse practitioners —through a virtual, AI-based digital front door that we employ to give patients 24/7 access to their cancer team.

We’re just an extension of cancer centers and we serve to help patients get through the entire process. Chemo, radiation, surgery, oral medicines, whatever you need, we’re there.

Kelly Choy-Wilson [42:29]

Wow, great.

For a patient that has an oncologist that has not brought up finances, what’s the best way for them to bring that up to their oncologist?

Pallav Mehta, MD [42:40]

Literally just like that.

Bring it up because I can assure you, the oncologist, they want to know this. They’re not going to know the answers. As Erin was answering those questions, I’m learning a lot by the way, so thank you for that.

The oncologist won’t know the answers most likely, but the fact that they know that, they want to help. Yes, they know they have to have certain treatments, but if they can just get some answers for patients they feel like they’re doing some good. I always say we treat patients not cancer, as oncologists. And if we’re treating patients, looking through that lens, finances are sometimes a bigger issue in patients’ minds than the cancer. And I’ve seen that.

Kelly Choy-Wilson [43:28]

Yeah, it’s unfortunate.

Erin, I just want to confirm with you that the services at PAF are not just for breast cancer but for other diseases and chronic illness as well.

Erin Bradshaw [43:42]

We serve almost a thousand different unique diseases last year. Unfortunately the areas that we’re talking about span across all different types of support needs,

Kelly Choy-Wilson [43:56]

What qualifies as medically justifiable for someone to remain on long-term disability after chemo?

Erin Bradshaw [44:06]

Typically it’s based on the insurance. Long-term disability has its own contract. So there you’re going to have to persuade the insurance company that you meet the standard of disability set forth under their plan or policy. You have to prove that you cannot perform the material duties of your regular occupation. Although some policies might require proof that you cannot perform any occupation that you’re suited for by education, training, or experience.

I think we’d have to invest a little time understanding where we’re at and after chemotherapy they might look at things like side effects, there are other comorbidities that you had prior, because we have to look at the holistic approach to see that. They’re going to probably request medical charting and reviews and, and validation to those type of questions about their role.

If you’re there and you’re having to provide that information, or even if you’re at a place where they might be denying or it’s coming to a close, seeking that out and investigating it sooner is ideal so you don’t find yourself in a gap.

Pallav Mehta, MD [45:25]

I’ll add to that just briefly, that when you, as a patient knowing the team — the oncologist, nurse, and nurse practitioners — let them know that there are certain words that have to be put in the documentation. It’s the simplest thing, but as oncologists, we’re constantly dictating notes all the time and, especially if that dictation is a couple of days later, we’ll forget to say certain things that might be so relevant to get those funds. So just make sure that the team is aware that this is what they need to get this and I assure you, it will get there.

Kelly Choy-Wilson [46:07]

Yes, that’s a very valid point. I actually sent a message yesterday and put exactly what I wanted in, in the documents. So that’s definitely a good point, to let them know exactly the wording of things that could help in your situation.

Let’s see, what else. What about financial support for out-of-pocket expenses for really beneficial support care like acupuncture and massage?

Erin Bradshaw [46:38]

Most insurance companies have a tendency to not pay for some of those elements. Acupuncture might be a little different, but we have to look at the plan design and what’s covered or considered excluded. You might find that information in the exclusion section. And outside that it’s kind of creative fundraising or support, from our experience.

I think if it’s prescribed, I think it changes it, versus, and it can still be prescribed, but it might be considered alternative care.

Kelly Choy-Wilson [47:18]

There are some organizations like Unite for Her where you get a passport for those type of services, massage, acupuncture, those type of items. That’s my input for that question.

Erin and Dr. Mehta, do you have any additional comments to finish up with? Or have we touched on everything already?

Pallav Mehta, MD [47:42]

I think we did. This is really, I think, comprehensive. It was helpful for me, for patients.

I think understanding your team, communicating with your team, knowing if there’s the right people on that team to address these issues and really not being shy about it. I think there’s a pride component that clearly goes into this when you’re dealing with cancer centers and a diagnosis like this, but just leave that at the door. No one is judging, people want to help. And the funds are there, so let them help.

Erin Bradshaw [48:21]

You’re already having to navigate this journey and this is a lot, so bring in the reinforcements and the support systems to help you. We wouldn’t expect for you to have a foundational understanding of all the potential assets that might be out there from the years of experience that some of us have that sit in our roles, or the support systems that exist. But we need to know. So just be OK and reach out, and hopefully we provide some everlasting education and guidance so in the future maybe you can be of aid to someone else that might need the help. It takes a team.

Kelly Choy-Wilson [48:58]

Thank you.

Thank you so much, Erin and Dr. Mehta, for joining us today and sharing your expertise. This was a great discussion.