The Treatment Landscape for Metastatic Breast Cancer Webcast Host: Andrew Schorr Guests: Hope Rugo, M.D. Robert Prosnitz, M.D.

Transcription

1 The Treatment Landscape for Metastatic Breast Cancer Webcast Host: Andrew Schorr Guests: Hope Rugo, M.D. Robert Prosnitz, M.D. Dikla Benzeevi Please remember the opinions expressed on Patient Power are not necessarily the views of our staff, or Patient Power sponsors or Patient Power partners. Our discussions are not a substitute for seeking medical advice or care from your own doctor. Please have this discussion you re your own doctor, that s how you ll get care that s most appropriate for you. Introduction How is your metastatic breast cancer identified and treated? What treatment type is right for you, and how do you play an active role in the plan? Coming up you'll hear from a leading hematologist/oncologist, and a radiation oncologist as they discuss the treatment options for metastatic breast cancer today. You'll also meet an inspiring woman with metastatic breast cancer. It's all next on Patient Power. Hello, I'm Andrew Schorr from Patient Power. Thank you for joining us for this second program in our series on metastatic breast cancer where we connect you with renowned experts and also inspiring patients. Joining us are a hematologist/oncologist from the West Coast and a radiation oncologist from the East Coast and also an inspiring patient, who you'll meet in just a second. I want to welcome Dr. Hope Rugo, who is the medical oncologist. She is director of breast oncology and clinical trial education for the UCSF Helen Diller Family Comprehensive Cancer Center. Dr. Rugo, thank you for joining us. Thank you very much. And also joining us is Dr. Robert Prosnitz. Dr. Prosnitz is assistant professor in the department of radiation oncology at the Hospital of the University of Pennsylvania, or Penn Medicine, in the Abramson Cancer Center. Dr. Prosnitz, thanks for joining us. My pleasure to be here. Dr. Prosnitz, we'll be back with you shortly as we discuss radiation oncology and its place for metastatic breast cancer. 1

2 And also joining us is someone who has metastatic breast cancer, and that is Dikla Benzeevi, who is 40 years old and joins us from the Los Angeles area, Studio City, California. Dikla, thank you for joining us. I think it would be helpful for women to hear your story because it is certainly inspiring. It began in what year first with stage III breast cancer? You were just 32. What year was that? That was in And what was found at that time? They found a tumor in my breast. It was about four to five centimeters large, and it was discovered initially through a routine gynecology exam, breast exam. Something was felt by my gynecologist, and she sent me to investigate it. But she also thought, well, you're young. Probably not breast cancer. Right. She thought it was a cyst, get it drained, no problem. You'll probably be out, in and out, no problem. But that isn't what happened, so that must have been quite the shocker. A very big shocker, a lot of firsts. The diagnosis, the stereotactic biopsies, the first IV, the first CT scan. It was quite a whirlwind at that time. So you have surgery and chemo and radiation with the hope that that got the cancer. What happened, though, afterwards? About six months after I finished a year of treatment I started having back pain that got worse and worse over time, and when I went to my oncologist regarding this they did some scans and discovered that there was a tumor in my spine. Oh, my. So that then brought up of word "metastatic" for you. Had you even heard of metastatic breast cancer? 2

3 In my initial investigation trying to become the, you know, instant expert on breast cancer I had heard about the different stages, but I thought I was done with breast cancer and on my road to recovery. I didn't expect it to come back again and to deal with now stage IV, you know, and chronic treatments. Right. This was just a terrible blow. So you were taking lots of medicines. First of all, your tumor type had been identified, and that was what we call hormone receptor (estrogen or progesterone receptor) positive, correct? That's correct. You were taking chemotherapy, hormonal therapy, and then we're going to be talking about radiation approaches as well. So with your spine you had radiation--you'd already had radiation for the breast earlier, but then you had radiation to your spine as well surgery. And that's right. I had severe, severe back pain where any sneeze or cough was like a explosion in my chest, and just walking hurt. So they did some radiation therapy to my spine which helped really alleviate a lot of the pain. And I had surgery for my spine due to--the tumor in my spine had grown so quickly that it had fractured the vertebrae and was threatening the spinal cord, and I needed back fusion surgery to correct that. Oh, my. All right. Well, that's not the only chapters in the story because then you go a couple years and you're being checked and you're taking medicines. Right. Where does metastatic breast cancer show up again? So a few years pass. I'm still in treatment. I'm consistently in treatment and in 2007 they found out that I had some tumors in my lung, and that was through routine scans that I did every three to four months since my spine mets diagnosis. Wow. So, well, happily, we're about three years down the road from that, right? 3

4 That's right. I mean, that's right. My new--the passion that has come up, my new passion is being a patient advocate and helping out my peers, my peer breast cancer survivors, especially women diagnosed under the age of 40 and their families, you know, journey through the process as easily and smoothly as possible. Well, we're going to talk more about that, and you're active in a number of groups, the Young Survival Coalition, a breast cancer group, and the I'm Too Young For This!, the young adult cancer group, the National Breast Cancer Coalition, and I know you do telephone support for women and particularly have groups that you deal with on the West Coast. Thank you for doing that. So before we meet our medical oncologist guest, Dr. Hope Rugo, I just want to mention, what's your outlook? I mean, a woman is listening to this program who is dealing with metastatic breast cancer maybe for the first time, maybe again, what propels you that you feel maybe is helpful when you talk to others? I want to let them know that diagnosis of metastatic breast cancer is not necessarily the end of the road. And there's many treatments and support centers out there of all different arenas that can help us journey through it smoothly and maybe more easily. It's--I just want to tell people it's not the end because a lot of people when they get the diagnosis they think, that's it, I'm going to die tomorrow, and it's not the case. Putting Metastatic Breast Cancer in Perspective Well said, and we're going to come back to you along the way and talk about from your point of view as a patient about how to have a successful relationship with your doctor or doctors. Let's continue our discussion with Dr. Hope Rugo from UC San Francisco. Dr. Rugo, so the situation is a very variable, isn't it? Put it in perspective about metastatic breast cancer because again a woman might start by thinking this is the end for me. Sometimes it moves very fast, but other times it could be many years. So help put it in perspective. I always tell women whether they're diagnosed with early- or late-stage breast cancer that if they are in a room with nine other women who have breast cancer that it's quite likely that there will be nine different varieties of cancer growth, treatment and expected outcome even. Obviously, what we would like is not to have young woman have recurring breast cancer that Dikla has experienced. 4

5 And I think that, you know, this of course is an issue that faces women again when they're making treatment decisions when they first get diagnosed with early-stage cancer, and as Dikla mentioned it really faces women in a very profound way when they get diagnosed with recurrent disease. We know now that there are many different subtypes of breast cancer, and our goals are to try and treat those subtypes specifically, understanding the biology of that cancer, so that an individual woman would be able to get treated in a way that would be most effective for that cancer's biology. Of course what we hope in the long run is that what will happen is that women like Dikla won't have recurrent cancer, that we'll cure it up front, you know. But that's still a little ways off. We're doing better and better. So what do we do with metastatic breast cancer? Well, the goal is to try and start with the treatment that's the least toxic but most effective. Sometimes we can't get both of them in there, but we try. And the idea is to try and control the disease with the best quality of life for as long as possible. So when you're a patient and you thinking, I have recurrent cancer and the doctors told me it's not curable and what am I going to do, the idea is to really understand what your treatment options are up front and understand that treatments have improved tremendously and that for many, unfortunately not all, but for many women who have advanced breast cancer that we can treat the cancer for a number of years with a sequence of different effective treatments. So as a patient what you really want to know is what kind of biology is my cancer? What kind of treatment options are there that might be available to me, and why are you deciding as the treating oncologist--like what are the factors that play into your decisions about what treatment you're going to give first second and third. And then of course, you know, in that whole scheme of things if the treatments that you hear about and the duration that they're expected to work are not what you want to hear, then it's always useful to be thinking about what kinds of clinical trials might be available for you as well that might be thinking outside of the box at new targets. Because the kind of treatment that Dikla is getting that's working for her came out of lots of clinical trials. And I know you're talking about this specific topic in another session. Yes, we are. We have a whole program with Dr. Gabriel Hortobagyi from M. D. Anderson, Dr. Julie Gralow from the Seattle Cancer Care Alliance. We'll talk about that in greater detail, and I hope our listeners will check that program out. Dr. Rugo, along the way we've used this term sometimes, "quality of life," but how do you define that? What do you mean by that? You know, that's a really good question because, you know, it could be defined many different ways, and there are even instruments that are sometimes used to try and make an assessment. But really what I mean in this--in the context of this conversation is up to 5

6 the individual. It's your perception of your quality of life. How do you feel? What's your pain, your fatigue? How can you function? What's most important to you? And that's what I mean by saying quality of life for women who have advanced breast cancer. Dikla, this term "quality of life," what does it mean to you? I think quality of life is a very subjective term, and for me it means how well do I live my life in the way that I want to. Can I do everything I want to do and to what extent, and that's how I define quality of life for myself and what I think others would imagine their quality of life to be, could they do what they want to do in their day-to-day routines and in their day-to-day life. The Landscape of Treatment for Metastatic Breast Cancer Related to current therapies that you have available now, Dr. Rugo, the landscape of those. It's growing. How do you feel about what you have now related to metastatic breast cancer? You know, it's a really good question because we can kind of divide up the treatments we give into three broad groups. So the first treatment we had for breast cancer was hormone therapy. It's really antihormone therapy. We have more options now than we ever had before, but there are still cancers that don't respond well to hormone therapies, so that's a big area of investigation of trying to look at prolonging response to hormone therapy or even reversing resistance. So that's the kind of clinical trial landscape, but what we have is more hormonal therapies available to us now than ever before, so that's really very good for us. The second big area of treatment of course is chemotherapy, and I think that as we've moved forward in understanding a little bit more--not enough, but a little bit more about what drives cancer growth and importantly resistance to treatment--and what I mean by resistance is that, you know, you give the chemotherapy and either the cancer responds for a few months or a year and then it starts growing again so you know that the cancer can now grow with that chemotherapy drug on board, or it just never shrinks from the very beginning, thankfully a less common situation. What we're understanding more now is what are the factors that make those cancers resistant up front or later. And having more chemotherapy options allows us to try and treat with drugs that might be more effective. So now we have more chemotherapy options than we have ever had before for breast cancer. We understand more about how to deliver those drugs in the most effective and least toxic way, which is really good. That having been said they still don't work for everybody, and they still don't work forever for women with advanced breast cancer. 6

7 And then that--the third option that we have are targeted agents. And of course hormone therapy and chemotherapy are targeted too, but we just use these terminologies to refer to the drugs. So there are agents that we have that target specific types of breast cancer and specific pathways that make cancers grow. So, Dr. Rugo, so understanding what a woman's specific biology is who now has developed metastatic breast cancer, so it used to be, well, where is the cancer, but now it's also let us understand, identify exactly what this cancer is. That's right. And, you know, the thing is, I think that what happens is when people find out that they don't have that HER-2 or their cancer isn't responding to hormone therapies they sort of feel like maybe their options aren't as good, but there are a lot of other targeted therapies that are being studied which we're very excited about. One that's very advanced for triple negative breast cancer, more that are being tested for hormone receptor positive and triple negative cancer, a lot of different targeted agents really based on that biology. Now, as you kind of alluded to, just making those decisions is not the end of the discussion. Obviously how well a patient is, what their symptoms are, what's important to that individual patient is as important as the decisions about treatment and the specific agents. The Importance of Defining What is Important to You Right. Let's talk about that for a minute. Now, Dikla, you have--you take a pill every day, you go to UCLA in your case very regularly for different infused therapies, and then you try to go about your life. Another woman might say, I just can't handle all of that, you know, I'd rather spend time with my family, less time in the clinic. And that's fair, right? Every--I'm sure you talk to many women, not everybody has the same point of view. That's true. Not everyone has the same point of view or, you know, the same feelings about types of treatment out there. What I try to differentiate when I do talk to them is how much the decision they make about treatment is out of fear or out of understanding what it is and making a clearcut decision. And that's a very distinct differentiation. And also how much it might actually affect their life. Do they have a realistic vision of what life with treatment is like, or do they have this exaggerated fear and nightmare of what it might be like. 7

8 Right. And I notice that a lot of the time their imagination just blows it way out of proportion to what it actually can be like, and they can maintain a good quality of life with many of the therapy choices. And I try to explain to them to at least give it a try before eliminating any choices. Dr. Rugo, go ahead. I just want to add in one little thing to that which is, you know, fitting in really nicely with that is that some people need more aggressive therapy, but for many women more is not necessarily better. So for example if you're having a lot of side effects from treatment it may be that a simple alteration of the way you're getting it or the type of therapy you're getting might work just as well and have less side effects. Dr. Rugo, so do you welcome that active discussion with a woman to try to draw her out, understand where she's coming from but make sure that she has an understanding of what's available, what could be altered, as you said? Yes, I think it's really important. We believe very much in a process called shared decision-making, and not just when a woman has a new diagnosis of early-stage breast cancer but at every step when we're trying to make treatment decisions for advanced breast cancer, when it's really important to say, you know, you can always make the choice not to do more intensive therapy at each step. On the other hand, here are the different options that I think are available to you, and here's the relative benefits and downsides of each one. And, you know, really I actually give patients a list a lot of times of the various options so that they can track along the way. And I think Dikla's situation is a really very interesting one, and it's so kind of her to be sharing the information that she has, her perspective, because, you know, she made decisions about different kinds treatments all along with her oncologist that were trying to give her, I expect, treatment that had the least toxicity but hopefully would control her disease. So what you do is you say, okay, I'm going to do this treatment, this is my decision, but we're going to keep a close eye on things, and if this treatment doesn't work then we'll go to another approach. And that can work very well and you really need to have that open communication with your oncologist. And I guess as in sort of a corollary to that, sometimes--you know, everybody has their own personality and brings their own 8

9 personality to the table. Sometimes oncologists might feel challenged by the patient when they bring up those questions, and I guess it's really important for, you know, the patient to feel comfortable that they can say to the physician, I want to discuss this a little bit more. I'm not questioning your judgment, but I just want to discuss it a little bit more and to have a fit that they feel comfortable with. That's really, really important at each step. Oh, I couldn't agree with you more. Dikla, I bet you do, too. You probably counsel women, empower them, if you will, to feel that they can play an active role. And this can come up more than once. I mean, it did for you, Dikla. There were different junctures, and it's like, here we go again, we need to have a discussion, right? Absolutely, and each time it's like learning it all over again, figuring out what's going on. And it also helps a lot, I think, for the patient or the breast cancer patient to not--to discuss it with their oncologist but also to speak to other survivors, to other patients maybe going through similar treatments to get a more practical perspective on what's going on and a well-rounded idea of what's going to happen. It is more of a team setting with a lot of medical professionals involved as well as their family and supportive community to help them make the right decision. This is not a time where you go through it alone or make those decisions purely on your own. It's really a time to open up and share it with the people around you and the medical professionals around you and make a good educated decision based on how you feel, your own personal perspectives, as well as the medicine out there. Areas of Evolving Treatment for Metastatic Breast Cancer Right. So true. Now, Dr. Rugo, a woman hopefully will live many years with metastatic breast cancer. We hope it can be treated for many people--everybody if it can't be cured as a chronic condition, and medical science and approved treatment regimes change over time too. So that's sort of an ongoing dialogue, right? In other words drugs may be used in a new way, there may be new things learned about them as well as new drugs, and a woman's situation may be evolving. There's a lot of moving targets here, aren't there? There are really a lot of moving targets and, I think, that's why I think it's so important to have an open conversation and to be able to look into what novel therapies are available or clinical trials are available at each step. So one of the things that's unfortunately true of trials is that they have certain eligibility criteria, so if you don't think about them before you start treatment it might not be available to you. On the other hand, a trial might just 9

10 not be the right approach for you, so, you know, and then for example maybe your doctor wants to start chemotherapy but you want to get a second opinion first and talk to another doctor. There are many different ways to approach that decision process. But one of the things that's really I think important for all patients to keep in mind is that these cancers are all very different. It's very heterogeneous, so we do sometimes have unfortunate situations where a breast cancer really is not responding to any of the treatments. And in that situation we really are failing at our attempt to try and treat this as a chronic disease and help women to live as long as possible with their best quality of life. But it's important to know that there are situations where we are successful and where we are not successful because I think sometimes women will feel guilty that their cancer isn't the right kind, you know, when they really don't have the ability to control that, and none of us do. Even now with those cancers that we can't treat as well and can grow through most of our treatments, we're having new options to treat them. That's why it's so important if you're in that situation to be thinking outside of the box, even more important than for other situations, and look at what kind of clinical trials are available. Now, monitoring goes on along the way. A woman is monitoring herself, and she is probably with metastatic breast cancer visiting the clinic pretty regularly for some treatment and also, Dikla, you even take a pill as well at home. What are the things that you're looking for? Obviously you're looking for any new sign of the cancer, but then you're monitoring things. What tests would a woman usually expect? Would it be like organ function, renal function? What's kind of the regular drill, if you will, Dr. Rugo, to see how you're doing? You know, it depends a lot on where the cancer is and how symptomatic a patient is. And I say this because it's important to exercise some caution. We see, you know, because we see a number of second opinions who come in from the communities around our area and farther away that what will happen sometimes is a patient will be feeling great and a small change on a scan is taken as progression, and the treatment is changed. And I think we want to keep our goals in mind at each step. In other words, you know, you want to live as long as possible with the best possible quality of life, and making rapid changes for small, you know, small changes that, you know, you're having trouble interpreting on a scan, is--may not serve the patient in the best light. But understanding the patient's symptoms, correlating that with your scans that you get periodically and the blood tests are as really important. For example we don't change treatment based on a tumor marker, these proteins that are released into the blood alone, when we don't see any change on the scan and the patient has no symptoms, because 10

11 that's not going to help the patient live any longer to treat a blood test. On the other hand, if the liver function is deteriorating then that's a situation where we definitely would want to change treatment. So each step you've got to have an open consideration. I think you have to be very aware of--be able to communicate with your physician about what symptoms you're having and what worries you because, you know, when you have bone disease, as I'm sure Dikla can tell us, you know, when you go out and do something and pick up a heavy object and you have shoulder pain, you know, the first thing you think of is, is it my cancer, you know. And sometimes you just have to wait a little bit and talk to your doctor and kind of get a feeling of whether or not it's a pulled muscle, you know. On the other hand, you don't want to be suffering without anybody focusing on what's going on. The scans, periodic scans, I think are really important because, you know, the--some situations like when changes occur in the lungs you may not have symptoms right away and you do want to know what's going on before you get significant symptoms. Right. So all the aspects are really important at a--as a--as an evaluation as you go along periodically, but also not reacting too quickly to something is important as well. Managing the Emotional Aspect So, Dikla, how do you--how do you control the emotional roller coaster for yourself, and what do you tell other women, because every time you go in for a scan or any time there's a new pain, you say, oh, my goodness. It's tough. The emotional part of it is very difficult to control and maybe it's not something that needs control. Sometimes I say emotions just need to be worked through. And I think a very crucial part of this is having a good support network around you, either from what you're--exists now or creating one for yourself by going to support groups specifically for advanced cancers, seeking a social worker, psychologist at the cancer center to speak to, whether it's a spiritual center that you belong to. Having someone to share your feelings with is extremely important. Having a patient navigator or advocate on your side to help guide you through every step of the process and explain things for you so that you know what questions to ask your doctor or what the information means in actuality, there is a lot going on, and it's very important to have that emotional support there for you. 11

12 Right. Let's just tick off some organizations. So we mentioned the National Breast Cancer Coalition. Correct. For younger women there's the Young Survival Coalition. That's right. There are a number of organizations and certainly at the clinic that's a question to ask as well, right, Dr. Rugo, is what resources are there to support me? Absolutely. And I just really want to echo what Dikla said. I think that having support around you is really very important, and depending on where you live a support group might not be the right way to go. You know, if the support group has people who are a lot older than you or a lot younger than you, who have different cancers, maybe it's not the right place. For many women it is, but not for all. And in those situations your community can play a very big role. Again, there can be a lot of support from your spiritual community if you have one, the social workers at your hospital or clinic may provide a lot of support. And then just the resource center, asking what's available in your area. Then as I think Dikla pointed out, the national organizations can be really helpful. I have a lot of patients who actually, you know, do web chats or blogs with a number of different national groups, advocacy groups that have been really helpful and supportive for them. And sometimes they'll come back and ask me a question about something that's come up that they didn't understand, and I just feel very pleased. Sometimes they just me that question, but I'm very pleased that those resources exist where patients can really talk to each other. And it brings up those questions about how different cancers are and what's out there and what's available. You know, not everything you read or hear is true, but then again it gives you a lot of ideas as well. I wanted to point out a couple of other resources that exist which may or may not be helpful for people, but the NCCN, the National Comprehensive Cancer Network is a number of different institutions in the United States and have guidelines for treatment for different malignancies, different cancers. And these are updated yearly and they give a lot of information. So that's a place that you can actually log on and get information that's patient-directed. There's a patient-directed part of the site. The other website that I think can be helpful, and Dikla needs to let me know also if you've gone there and didn't 12

13 think it was helpful, but the NCI and the American Cancer Society have a lot of patient information areas where you can read and just get some background information about the topic you're interested in. And I think that, you know, those are improving all the time. They're updated all the time, and I think they're really valuable resources. How to Facilitate Open Communication with Your Doctor Right. I'm happy to say that Patient Power is a partner with the NCCN. And, so, I just want to say, you know, there are people who will encounter a doctor who maybe not is as open as you, Dr. Rugo. Any counseling you would give there when they're just not feeling the open communication? I think, and I was referring a little bit to that before, it's really a challenge. I think--you know, and I've seen it actually in my communications with physicians or heard it from patient where sometimes, you know, people just take it personally. They don't want to be questioned, or they feel like you're challenging them, you know. And, as I said, you know, people bring their own personalities to the table in this situation. I mean, nobody is above it. So what I would recommend when that happens where you feel like there's some resistance to questions and you feel like you can't get the answers you want, I think there are two things that you should do first. One is to--most of the practices have nurse--nurses who work with the physicians or some kind of physician extender staff, and I would talk to them. See what their perception is about what you're asking. You know, does this--are you being too challenging? Because sometimes, you know, people will come with me with--and sort of argue continuously over time, and, you know, I'm willing to argue for a long time, but some people I think might find that very, very difficult to deal with, so I think it's good to get that little bit of feedback about the kinds of questions you're asking. Find out if there are other resources in the practice where you can go to ask questions, and just make it clear what your interest is in asking the questions, not challenging the doctor but getting more information to treat your disease, you know. And then sometimes those people in the clinic can be very useful in just clearing up any misunderstandings in communication, go back and talk to the physician and improve things. The second thing I think that the patient needs to do is just go back and say, okay, you know, what is it that I really want to know here and what's most important to me in terms of this communication. And then I think that if it just isn't working out you need to go and get another opinion elsewhere. Don't worry about offending your doctor because I think, you know, a physician who really cares about what's going on with that patient needs to be open to the patient seeking advice elsewhere as well. We're very open to 13

14 that, and I will often talk to my colleagues elsewhere when patients have very difficult, complicated situations where there's no right answer just to bring to the patient many different opinions. And I get a lot of questions from doctors out in the community who are on their own and just have questions that they want to bring in, and we're all very open to discussing those kinds of questions. So, you know, I think when you bring this up you've got to be willing to make a change if it's not working out for you because in the end it's your disease and your life, and you want to make sure that you feel comfortable with the decisions you're making and with the decisions your practitioners are making. Great advice. Great advice. We're going to hear more from you later on in the program, Dr. Rugo, and you too, Dikla. Okay. I want to mention that coming up in the next segment of the program, we've talked about, Dikla, you had surgery to fuse your spine when you had a fracture from the tumor there and had radiation, and so many women do need radiation along the way, could be to the bone, sometimes to the brain. And so our other expert is Dr. Robert Prosnitz from the Abramson Cancer Center and Penn Medicine at the University of Pennsylvania, and we'll be back with him right after this. The Role of Radiation Welcome back to Patient Power. In our discussion about current treatment for metastatic breast cancer we've had a great discussion with Dikla Benzeevi from Los Angeles, and Dr. Hope Rugo, renowned breast medical oncologist from UCSF Medical Center in San Francisco. We'll hear more from them shortly. Now let's get back together with Dr. Robert Prosnitz, who, as we said, is a radiation oncologist. He's an assistant professor in the department of radiation oncology at the Hospital of the University of Pennsylvania in Philadelphia. He of course is part of the physicians at Penn Medicine in the Abramson Cancer Center. Dr. Prosnitz, let's understand the role of radiation oncology. We've talked about metastatic breast cancer. We wish we had a cure, and unfortunately right now we don't, so there are the systemic therapies that we've been hearing about. Where does radiation come in? Well, Andrew, radiation therapy has a number of very useful roles in the treatment of patients with metastatic breast cancer. As you and your listeners probably know, 14

15 chemotherapy and other systemic therapies are clearly the mainstay of therapy for patients with metastatic breast cancer, but there are a number of instances in which radiation therapy can prove quite useful. Two of the most common instances are in the palliation or pain relief of bone metastases, and the second instance would be in treatment of patients who have--who develop brain metastases or a spread of the breast cancer to their brain. Now, how would someone know or how would it be discovered that there's--there are these problems and that radiation then becomes recommended? Let's talk about bone metastases first. The most common presentation for patients with bone metastases is as you would expect bone pain, and this is most often in the spine, pelvis or shoulders. And pain in the spine typically presents with back pain. Pain in the pelvis often is involving the hips, either the proximal or--proximal femur or what's called the acetabulum. Those are the two components of hip joint. In any of these areas the patient can develop a skeletal bone metastasis which leads to pain, and this is typically a symptom that they would bring to the attention of their medical oncologist who would then obtain appropriate imaging in that area to confirm that a bone metastasis is present. And if that is present and the pain is not responding to chemotherapy, radiation therapy can be very useful to relieve that pain. Radiation Versus Systemic Therapy What is radiation able to do that maybe the systemic therapy couldn't do? Well, radiation therapy is a more focal treatment than systemic therapy. Chemotherapy and other systemic therapies have the advantage of getting into the bloodstream and traveling throughout the body to kill cancer cells wherever they may be. It tends to be more effective however against a smaller burden of disease. If a larger focus of cancer develops, let's say in a bone, chemotherapy may not work as well there, and if a patient has focal pain, let's say in their low back, and an MRI scan demonstrates metastatic disease there, radiation therapy is often the quickest, most effective way to address pain related to a bone metastasis. Now, we've talked about bone. Tell us about brain, and does it vary if it's just seen in one spot or it's thought to be more microscopic in its spread or numerous places? Well, brain metastases do have a number of different presentations. We'll talk about the symptoms first. Symptoms can range from more constitutional symptoms, such as 15

16 nausea or weakness or lethargy, to more focal problems, like headache or any number of specific neurological issues including weakness or numbness of an arm, leg, hand or foot, or on occasion seizures. Any of these neurologic symptoms, constitutional symptoms or headaches will often prompt a physician to order either a CAT scan or an MRI of the brain, and that would lead to the diagnosis of brain metastases. Now, how we treat those does depend on a number of factors which include kind of the patient's overall, we refer to as their performance status, but basically how functional they are, the number of--the number, location and size of the brain metastases, and the third factor would be how well the patient's disease is being controlled by their treatment in the rest of their body. So for example the patient has only a very small number of metastases, let's say three or fewer, and they're relatively small in size, such a patient would have the option to undergo what's called stereotactic radiosurgery, which is a highly focused dose of radiation either delivered as a single treatment or over just a few treatments. That would be one end of the spectrum. Alternatively, a patient with a large number of brain metastases would generally be treated with what's called whole brain radiation therapy, and as the name would imply the entire brain is treated in that circumstance, typically over a period of two to three weeks. Now, with these problems that come up, a woman obviously has a hope to live a long time with systemic therapy and as-needed radiation, can this only be done once or how does it work, either radiation to the same spot or to have radiation for another spot? Generally speaking, radiation therapy can be given to a specific location in the body. Generally it is only given once to a specific location in the body. On occasion radiation is given a second time around, but typically with the first course of treatment we are administering the maximum safe dose of radiation. We want to have the highest probability or chance of relieving the symptoms that the patient has presented with, be it back pain from bone metastases or neurologic symptoms of brain metastases, so we're giving the maximum safe dose the first time around. Now, with the passage of time the body's tissues do recover to some extent from the radiation they've received, and on occasion we will treat a second area, but we never take that decision lightly, and it would generally be done a second time around only if no good alternatives for therapy existed. Having Realistic Expectations Dr. Prosnitz, let's talk about what might be a reasonable expectation. If, let's say, there had been cancer pressing on a woman's spine and the team decided that radiation could be helpful and there had been pain, from your experience, and I know it varies, how much 16

17 relief might a typical woman get? How much of a difference could it make to let them go back to being mobile and having a life that is just more full for them? Well, Andrew, radiation therapy is quite effective in the relief of pain due to bone metastases. That's an area in which it works extremely well. Generally we see about three quarters of patients having either complete or partial relief of their back pain, and quite often we see a reduction in the need for narcotic pain relievers and significant improvement in their functional abilities. Now, what about in the brain? Now, we described the situation being different, but if there was a lesion or two or three that was having some effect, the ability to shrink these, how pronounced could the improvement that would be for a woman? It's interesting. Breast cancer is rather unique among different solid tumors in that patients with metastatic breast cancer, some of them can have a long survival with metastatic breast cancer. In terms of brain metastases, the size and number is really the most important prognostic factor in terms of how that patient is likely to do going forward. For a patient with a small, single or less than three metastases who receives stereotactic radiosurgery the chances of control of that disease in the brain are quite excellent, and many people favor giving stereotactic radiosurgery first and simply observing the patient going forward with additional MRI scans, let's say, approximately every three to six months afterwards. And in some cases if the disease does reoccur in the brain additional stereotactic radiosurgery can be administered, or whole-brain radiation can be administered. So that's a very favorable situation. On the other hand, if a patient presents with multiple brain metastases and large brain metastases and already is quite sick at the time of their presentation, that is a very challenging situation to treat, and unfortunately most patients who have that extent of disease in their brain do expire on the order of three to six months after radiation therapy. How the Different Modalities Work Together Well, let's hope that our listeners can have a long life despite the fact of a diagnosis of metastatic breast cancer. Now, they have probably several members of the healthcare team. You mentioned medical oncology, and we have Dr. Rugo with us. From your point of view, how does it work together because these are modalities that are often used with the same patient? So how does the communication work and what should a woman expect from her team as far as communication? 17

18 Well, I think close communication and collaboration between medical oncology and radiation oncology is essential in these cases. Typically in a palliative or symptom-relief context we generally don't administer chemotherapy and radiation therapy at the same time, or concurrently would be the medical term that we would use, the reason being that the side effects can be elevated when chemotherapy and radiation are given in combination. So if a woman is undergoing systemic chemotherapy for metastatic breast cancer and the need for radiation therapy arises, typically the systemic therapy is halted if it is--if that therapy is chemotherapy. Now, if a woman is receiving endocrine therapy for her metastatic breast cancer, radiation can be given in conjunction with endocrine therapy, but it would--but chemotherapy would generally be held. And what about some of these newer targeted therapies? There are some agents that we do know can be administered safely with radiation therapy. Other targeted agents, their safety in conjunction with radiation is less well known. I think generally those targeted agents are frequently given in combination with chemotherapy and less often used alone, so in that setting all systemic therapy would be temporarily held while radiation therapy is administered typically over a course of two to three weeks, and following the completion of radiation therapy the systemic therapy could resume or a different type of systemic therapy could be initiated. Possible Side Effects of Radiation Now, we talked about the relief that many women might feel. What about side effects? These are--this is a powerful modality, radiation, so tell us about side effects. So first of all I think it's helpful for patients to understand that radiation therapy is at the time of its administration completely painless. It's just like a regular x-ray. It differs from a regular x-ray in that the radiation is considerably higher dose and stronger when it's used for therapeutic purposes as opposed to diagnostic purposes, but essentially it can neither be seen, felt or--or smelled or sensed in any way. Nevertheless obviously there are side effects to radiation therapy, and these are generally discussed at length prior to initiation of any course of radiation. The side effects do depend greatly on the site of the body being administer--being treated and will differ from site to site. For example if a patient is receiving radiation therapy to their thoracic spine, which is the part of the spine in the chest area, typically that would be done with one radiation beam coming from the back and one radiation beam coming from the front, and the most significant side effect for that type of treatment would be a mild to moderate irritation of the esophagus, which sits just in front of the spine. And 18

19 typically towards the end of radiation therapy patients may experience a little bit of sensation of difficulty swallowing or sensation perhaps that food is not passing through their esophagus quite as easily. Those, any irritation of the esophagus generally resolves within a week or two after completion of radiation and is seldom a severe problem. Skin irritation for treatment--during treatment of bone metastases, whether they're in the spine or the hip generally is fairly mild, and symptoms such as any nausea or vomiting are quite uncommon, and blood counts are typically not affected very much by radiation unless a large area of bone marrow or a long region of the spine is being treated. Dr. Prosnitz, so a woman has a diagnosis of metastatic breast cancer and may feel some pain or maybe they have some dizziness or some other effect on their brain. They may say, well, look, I have this serious diagnosis and this is the way it goes, but it sounds like with radiation oncology there could be some relief and it's important to have that open communication with your doctor. Andrew, I agree with you completely on that, and I think, you know, certainly patients with metastatic breast cancer are just like the rest of us in terms of there are normal aches and pains that occur in the course of our daily living and on the one hand I don't want women with metastatic breast cancer to be concerned over every little ache and pain that they feel. The pain that generally requires treatment is pain that is getting progressively worse and it really doesn't go away. That would be more indicative of pain resulting from a bone metastasis. I think it's important for women to understand and have a clear understanding through discussions with their cancer physicians exactly what organ systems are involved by their disease and how their disease is responding to whatever therapy that they're receiving. So if a woman has involvement of her skeleton she should know that and then just be aware if she develops pain that's getting worse and is becoming severe in any of the sites we mentioned, the back, the shoulders, the hips, that this should be brought to the attention of her medical oncologist and further investigation of that pain should take place. Situations Where A Woman May Need Radiation Right by the Breast Dr. Prosnitz, we talked about radiation for the bones and the brain, but could it come up that a woman with metastatic disease would need it right by the breast or on the breast? This is a situation that does occur from time to time, Andrew. In some instances a woman may have metastatic disease at the time of her initial presentation, and when that's the case it's generally not felt to be very helpful to do a mastectomy or do any 19

20 aggressive local therapy. Generally systemic therapy is administered, and any local disease that may be present is monitored. If it becomes worse the options for treatment of disease in the breast, let's say the patient develops worsening pain, bleeding or other problems from disease in her breast, options for treatment would include palliative surgery or palliative radiation. There are other situations in which a woman is treated--initially thought to have early-stage disease, undergoes a course of treatment for that and then several years later perhaps develops metastases. And in some cases a local regional recurrence, that is disease coming back in the breast or in the lymph node regions that are nearby to the breast, can occur at the same time as distant metastases develop. In those situations, that's another situation in addition to radiation of bone metastases or brain metastases that palliative radiation therapy can be useful. Sometimes enlargement of lymph nodes in the armpit or near the collar bone area can cause pain and discomfort, and palliative radiation can be useful in that situation. And sometimes disease that is progressing in the breast itself requires palliative treatment with radiation. Closing Thoughts Dr. Robert Prosnitz, thanks for explaining that. It was my pleasure. Dr. Rugo, you've been speaking with us earlier and listening as we heard from Dr. Prosnitz. We've covered medical oncology. We've covered the emotional issues and management. We've talked about radiation oncology. All try to help women live well even if today we can't cure metastatic breast cancer. What would you like to leave women with who have been listening? I think that the most important thing to keep in mind is the goals of treatment, which are to live as long as possible with the best quality of life, and that for that to occur there needs to be open communication with you and your healthcare providers. You need to have the right support both in the clinic setting as well as outside, as we've talked about. And then I think you need to at each step of the way think about what's most important to you and what the most important information that you want to have at each step is. And then I think to look forward with hope that we're making tremendous progress in the treatment of breast cancer. It's not curing women with metastatic disease, but women are living longer now than ever before. And we need to always be thinking outside the box and looking forward to what clinical trials, what new agents, what new approaches are out there. 20