Dr. Nancy Lin
Dr. Nancy Lin is a medical oncologist in Boston, MA at Brigham and Women’s Hospital and Dana-Farber Cancer Institute. She specializes in the care of patients with all stages of breast cancer. Her research focuses upon improving the outcomes of people living with metastatic breast cancer, including a particular focus on the challenge of breast cancer brain metastases. She has led multiple clinical trials which have led to new treatment options for patients with breast cancer that has metastasized to the brain.
Dr. Nancy Lin is a medical oncologist at Dana-Farber Cancer Institute (DFCI) and Associate Professor of Medicine at Harvard Medical School.
Dr. Lin received her medical degree at Harvard Medical School and subsequently completed her residency in Internal Medicine at Brigham & Women’s Hospital and a fellowship in Hematology/Oncology at Dana-Farber/Partners Cancer Care. Since 2018, she has served as Associate Chief of the Division of Breast Oncology at DFCI. Dr. Lin’s focus is on developing novel targeted therapies for patients with advanced breast cancer and exploring mechanisms of drug resistance, with a particular interest in patients with breast cancer that has metastasized to the brain.
Dr. Lin is leading multiple ongoing and planned clinical trials evaluating a variety of targeted approaches in patients with metastatic breast cancer. Her work is highly collaborative and involves close working relationships with clinicians, laboratory investigators, and patient advocates. Dr. Lin’s honors and awards include a Young Investigator Award and Career Development Award from the American Society of Clinical Oncology. She is a member of the Massachusetts Medical Society, American Society of Clinical Oncology, Alliance for Clinical Trials in Oncology, and Translational Breast Cancer Research Consortium.
Dr. Nancy Lin – Video #1 – Medicine Based Treatments for Breast Cancer
So I just want to welcome everyone that’s joining us today. My name is Lianne Kraemer. I am a patient advocate and we are going to do an interview today with medical oncologist, Dr. Nancy Lin. And before I formally introduce her, I’m going to read her bio to you. Dr. Lin is a medical oncologist specializing in the care of patients with all stages of breast cancer.
Her research focuses upon improving the outcomes of people living with metastatic breast cancer, including a particular focus on the challenge of breast cancer, brain metastasis. She has led multiple clinical trials, which have led to new treatment options for patients with breast cancer that has metastasized to the brain.
Dr. Lin received her MD from Harvard Medical School in 1999. She completed her residency in internal medicine at Brigham and Women’s Hospital, and went on to complete fellowships in medical oncology and hematology at Dana Farber. In 2005, she joined the staff of Brigham and Women’s and Dana Farber where she is medical oncologist and clinical investigator in the breast oncology center.
So it was wonderful to have you join us.
Thank you for having me Lianne.
Of course. For those who probably don’t know, Dr. Lin is actually my oncologist and she is wonderful and does specialize in the treatment of brain metastasis. But you treat as your bio mentioned, all stages of breast cancer. Can you tell me a little bit about your role as a medical oncologist, what you do?
So as a medical oncologist, our focus is on the medicine-based treatments for breast cancer, whether early stage breast cancer or metastatic breast cancer. And so those medicine-based approaches can be medicines like hormonal therapy, chemotherapy, or targeted therapy. And in general, except for the initial part of therapy where often the breast surgeon is the so-called quarterback for much of the rest of the course of treatment. In patients with metastatic breast cancer, in general, the medical oncologist serves as a sort of quarterback of the team.
So after early stage treatment ends or with a diagnosis that begins with metastatic breast cancer, can you talk a little bit about what happens with metastatic breast cancer?
Right. So with metastatic breast cancer, our goals are to try to help people live the longest and best quality of life possible. And we do that really in cooperation or collaboration with the patient usually going from one treatment to another in hopes that each treatment will work for a good period of time and that we can string out one treatment after another to allow people to live long lives in many cases, although not all cases, even with a diagnosis of metastatic disease.
So early stage, there’s a curative intent where with metastatic breast cancer, it has spread beyond the breast. And at that point the intent is to provide care that can extend life.
That’s right. So in general, for metastatic breast cancer, never say never, but in general, our goals are not so much to cure the cancer, but to really keep the cancer under control for as long as possible so that people can experience sometimes extended survival, even in the setting of metastatic disease.
Dr. Nancy Lin – Video #2 – What are Brain Metastases
So when breast cancer spreads, it likes to go to a couple different places. It likes to go to the brain, the bones, the liver, the lungs. Can you tell us a little bit about what brain metastases are?
Right. So brain metastasis are tumor cells that have come from some part of the body.
In the case of breast cancer, usually originally from the breast although the cells could have migrated from breast cancer that’s gone to the liver or breast cancer that’s gone to the lung, but ultimately those breast cancer cells land in the brain. And when they do that, they can either land in the so-called parenchyma of the brain, which is the actual brain tissue itself.
It shows up generally as lumps or spheres in the brain, or it can land in the spinal fluid. This is otherwise known as the CSF and that leads to something that we call leptomeningeal disease, which is cancer that is basically floating in the spinal fluid. And even though they’re both, in some ways, brain metastases or cancer in the central nervous system, they are quite distinct in the kinds of symptoms that people have and also in the types of treatments that we offer.
One of the common questions that comes up is: What’s the difference between a primary brain tumor and breast cancer brain metastasis? And the reason we care where the cancer came from is because the cancer keeps the characteristics of where it came from. So a breast cancer still responds to breast cancer treatments, even though it’s in the liver or the bone or the brain.
And it’s not going to respond to treatments necessarily for cancers that start in the brain or start in the bone. That’s why we put so much attention on pathology. Like, where is this cancer from? Because it really affects what we think about for effective treatment.
Thank you so much for mentioning that as somebody with brain metastasis are often by myself, you know, describing to people what that difference is, it’s hard sometimes for people to understand.
That was a brilliant explanation. How common are brain metastases?
So for people who have early stage breast cancer, it’s not that common as the first place for cancer to show up. So, you know, for somebody who has either stage one or stage two breast cancer, less than 5% of the time the cancer will show up first in the brain.
So that’s a reassuring number if you have early stage breast cancer. For people who have inflammatory breast cancer, that chance is higher, probably like 10% to 15%. And for people who have metastatic breast cancer, at least when the metastatic breast cancer is first diagnosed, maybe about 5% to 10% of the time is there cancer in the brain. It’s not any more than that, but over time, the chance can increase.
And so for people who have HER2 positive breast cancer, for example, if we look from the time somebody is diagnosed with metastatic breast cancer, to the time they die of breast cancer over that period of time, about half of people will develop cancer in the brain. And similarly, if we look at patients with triple negative breast cancer, that’s already metastatic, somewhere around at least a quarter and in some cases up to half. Somewhere in that general ballpark of patients will develop brain metastasis over time. It’s actually less common in people who have estrogen receptor positive breast cancer that’s HER2 negative. In that case, the lifetime risk of developing brain metastasis, even in the setting of advanced or metastatic breast cancer is estimated at about 10% to 15%.
So you mentioned that when you receive your initial diagnosis of having metastatic breast cancer, that it’s not as common to have it as a first site when you’re diagnosed.
Why does it become more common over time?
We think that it probably becomes more common over time as people live longer, because it’s almost like a chance happening. Cancer has to break off, find its way into the blood vessels, get into the brain, figure out how to cross the blood brain barrier and set up shop.
And, you know, cancer cells are breaking off into the bloodstream all the time, but very few managed to do all of those steps, but the longer somebody lives with their metastatic breast cancer, the more time there is for these repeated attempts to be – I hate to use the word successful to make it to the brain.
So we see that, for example, in HER2 positive breast cancer, where, you know, many people survive more than five years after a diagnosis of metastatic disease. That’s I think why we’re seeing a part of why we’re seeing an increased risk, but on top of that, HER2 itself probably has, and we don’t know why yet, but there’s some reason scientifically that HER2 from a biological standpoint, seems to allow cancers to get into the brain and set up shop there more easily because even people with ER, positive HER2 negative breast cancer, who also, you know, very commonly will survive five or more years after a metastatic diagnosis, they’re still at lower risk of brain metastasis than patients with HER2 positive disease surviving for the same amount of time.
Dr. Nancy Lin – Video #3 – How are Brain Mets Diagnosed
How are brain mets typically diagnosed?
Right now, the most common way that brain Mets are diagnosed is if a patient reports symptoms, and then that prompts usually an MRI scan of the brain to look to see why those symptoms appeared. A lot of people ask me about whether memory loss or forgetting where the keys are, you know, are a sign of brain metastasis.
It’s a common question because it’s a common occurrence. But that’s not the way brain metastasis usually presents. So the most common symptom is headaches. If we see headaches that are associated with nausea and let’s suppose somebody who’s on their seventh cycle of the same chemotherapy and all of a sudden, they’re nauseated that’s not right. If somebody wasn’t nauseated for the first six cycles, they shouldn’t really be nauseated for the seventh cycle. That really raises a red flag, especially if their headaches are associated or sometimes people notice that their coordination or their balance is off or they’ve had a fall.
There’s no reason that a 34 year old woman should trip off the curb for no reason. It really raises the red flag. Is there some underlying issue that is need for concern? So I have a very low threshold to image the brain in somebody who has metastatic breast cancer.
Any of those symptoms, headaches in coordination and balance problems, et cetera, certainly any weakness on one side versus the other, and also seizures, which are not so common, but any of those kinds of symptoms should prompt a brain MRI.
You mentioned seizures. How do you know specifically? Cause that’s, in the community that I talked to who have brain metastases, that is certainly a really big worry for them.
Do you know approximately how many? You say they’re not very common.
So when people have looked to see, you know, of the symptoms that were the first symptom of a brain metastasis, but 10% of the time around 10 to 15% of the time, depending on which study you look at, is seizure the first symptom. So it’s not rare, but it’s not the most common, whereas around 70% of people have headaches.
So as far as medication for seizures, it’s not something you would put a patient on prophylactically, you would wait for them to have an actual seizure.
That’s exactly right. So you know, it’s quite reflexive to think that, when you have a patient who has a new brain met on a scan to immediately put them on an anti-seizure medicine, it feels like the right thing to do, but there actually have been clinical trials, randomized clinical trials showing that there isn’t a benefit conferred with that approach. And so the national guidelines, if somebody has not ever had a seizure, at least for breast cancer, brain metastasis is not to routinely give anti-seizure medicine.
There are always exceptions to the rule. And certainly if somebody is going to the operating room and there’s going to be potentially bleeding, oftentimes the surgeons will temporarily put people on a brief course of anti-seizure medicines. Similarly with certain types of radiation, it’s not uncommon if there’s a concern, for a larger lesion to put somebody temporarily, but, you know, in terms of long term indefinite use of anti-seizure medicine, we try to stay away from it, except for patients who have had seizures.
Okay, that makes sense. So for screening or for diagnosis it seems like it’s something dependent. There’s no guidelines for regular screening, even in those who are more likely to develop brain metastasis. Whereas when you have metastatic disease there is the schedule for screening.Can you explain a little bit about why that is?
Yeah, I mean, this is a really important topic. And I think it’s a topic that we just, as a community, have not addressed in terms of clinical data or clinical trials, as well as we could have. We’re trying to do it now. There are actually some trials now, prospective trials, trying to develop evidence to see whether there are benefits to screening, but right now there’s no prospective clinical trial evidence to prove a benefit.
And there’s sort of conflicting evidence if you look backwards in time. So if you look backwards in time, you see of patients who have brain metastasis, could we have made a difference if we did screening on the one hand there’s data, that Dr. Ayal Aizer who is one of the radiation oncologists that I work with, that he generated, where he compared people at our institution who have lung cancer, brain mets, versus those with breast cancer, brain mets, and the differences for lung cancer patients, they usually get screened.
What he found is with patients with lung cancer, their mets are usually diagnosed when they have fewer brain mets on average, the brain Mets are a little bit smaller on average, they tend to need less whole brain radiation. So those are all really good things. And that is in fact what led to the trial that he’s currently running.
But there have been other groups that have looked backwards in time to say, well, if people who had brain mets found because they had a required brain MRI as part of a clinical trial, for example, you know, some other reason they had a brain MRI and they didn’t have any symptoms. And they look to see is survival longer in people who had brain mets found by screening versus those with brain mets found when they had symptoms. And those studies have shown no difference in survival. So that’s why there’s this debate. And if you go backwards in time and medical records, you can’t ask about quality of life and you can’t ask about neurological symptoms or cognitive symptoms because they can’t do that retrospectively back in time.
And so that’s the problem right now. It’s really like a data problem. And so hopefully, you know, there are three trials now going on across the world to try to look at the role of screening MRI. You know, right now we say we don’t do it. And I don’t usually do it because there’s no data, but it’s not that there’s data that it’s not good.It’s that there’s no data. Or no prospective data. I hope that not so long from now, we will have data. We can actually make a data-driven recommendation. That would be optimal, for sure. To have something that guides us rather than making a decision on the lack of data, which is sort of challenging.
I assume there are risk factors for getting brain metastases. Can you speak to that a little bit?
Right. So tumor subtype is one of the risk factors. So if you have triple negative, which is estrogen, progesterone and HER2 negative or HER2 positive, I’m throwing out all these like jargon for subtypes and I just want to preface by saying, if you don’t know what subtype you are, you should ask your doctor and find out because everything in metastatic breast cancer treatment depends on the subtype. It’s something that is a good thing to know for your own care. But the other types of risk factors are things like being young. Young age does seem to increase the risk of brain mets. Having metastasis in the lungs seems to increase the risk of brain mets. And also having inflammatory breast cancer. So there are some of those risk factors. And then finally, for a specific type of cancer in the brain, what I talked about, which was this leptomeningeal disease, a cancer in the spinal fluid lobular breast cancer, which is a type of appearance under the microscope, seems to be more likely to do this.
Dr. Nancy Lin #4 – Treatments for Brain Mets
Well, why don’t we talk a little bit about treatments? So when you get a patient that’s newly diagnosed, what are the considerations and how do you go about treating it? I know this is an extraordinarily complex question, but let’s see if we can break it down and, and talk about how we treat it.
Right. So I think the reason it’s so complex is because we actually have multiple different types of treatments that could be considered. And normally when we think about how we treat cancer in the liver that’s worse, it’s just the medical oncologist trying to decide with the patient should we give drug X or drug Y or drug Z. Although it’s not an easy decision, it’s basically two people, one doctor and one patient talking through the options. What’s really different about the brain metastasis management is it’s oftentimes multiple doctors plus the patient thinking about what’s the right approach, because it may be that radiation is a possibility. It may be that surgery is a possibility. There are even different types of surgery, like regular surgery and this type of treatment called LIT, and there’s different types of radiation. Then there’s chemotherapy and targeted and systemic therapies. So, for any one patient, it may be that all of those things are theoretically possible to do. You have to make a decision together, as to which of those options at this point in time makes the most sense.
So to just give you a couple of very concrete examples, if somebody comes in and they have, let’s say they have a new seizure and they go to the emergency room and they have one very large lesion in the brain. Usually we would recommend that person have surgery first. That person usually would get some radiation to the margins around the surgery, after they recover from surgery.
Then after that, there’s some systemic therapy given. That’s like three different types of doctors to treat that one patient. If you have somebody who’s already gotten radiation, maybe she’s not a candidate for surgery. And now has several new brain metastases such that the radiation option would normally be whole brain radiation, but that person, you know, is very concerned about the side effects of whole brain radiation.
They want to ask if there is some chemotherapy or targeted therapy option? Well, then the radiation oncologist and the patient and the medical oncologist have to weigh well, what is that systemic option? What is the likelihood it’s going to work? What’s the risk if you don’t, if it doesn’t work. So these decisions become quite complicated and they really require that there’s a functional team of people who are going to work together.
It’s also one of these kinds of scenarios where often there’s not necessarily one right answer. It depends a lot on what’s important to the patient. So, if what’s important to the patient is avoiding whole brain radiation at all costs, there might be a different answer than if what’s most important to the patient is I want as long a period of time before I have to deal with anything else going on in my brain.
Those are really important discussions that we have with patients about what is their most important goal, because we might have different recommendations, but depending on what the patient’s most important goal is.
Yeah, that’s complicated. So it sounds like what you’re saying is that it’s first and foremost, really important to have a team that is working together in a comprehensive manner to collectively decide along with the patient about what is the best approach for treating their particular brain mets.
That’s exactly right. I think this is one of the things that I hope that this initiative will help people find, because I think it is hard as a patient to find the right team. And yet that’s one of the most important things that really affect the quality of someone’s care.
Yeah, I agree. It’s really important. And it can be very difficult as a patient if you don’t have that, because that leaves the burden of coordinating care to you rather than a team that’s already established. So that can be very difficult. With your role as a medical oncologist, you focus on the drug side of the treatment, although you’re involved in collaborating with the team, you’re making decisions about treatment. And so I wanted you to talk about the drugs that are available to treat the brain. If you could also discuss how the blood brain barrier affects the drugs that are available to use, that would be great.
So the blood-brain barrier is something that we’ve evolved to basically keep toxins out of our brains. And in the normal brain, there are these barriers or junctions that are very tight and they really keep out a lot. What happens though, is that in brain metastasis, those barriers get broken down because the tumor sort of breaks through those barriers.
And so as it turns out many drugs that don’t get into the normal brain all that well, actually get in decently enough in brain metastasis that we can see some activity. So one of the things that has set back the field for a long time, is making the assumption that if something doesn’t cross the normal blood brain barrier, it can’t possibly work.
And we now have many examples that that’s not true. So ultimately what we have to do is just test the drug on people who have brain metastases and see if it works. But there are some treatments that work and I’ve listed a few of them here focusing on HER2 first. So for HER2, you know, the drug that probably comes to mind most often is a medicine called to Tucatinib, which is an oral pill.
It targets HER2 kind of from the inside out, whereas Herceptin targets HER2 from the outside in. Tucatinib is typically combined with an oral chemotherapy called Capecitabine, along with IV Herceptin. This combination of three medicines has been shown to be effective in patients with brain metastasis. And this has been shown in a randomized trial where it was shown to be better than just Herceptin plus chemotherapy. So it wasn’t a randomized trial against nothing. It was a randomized trial against a normal, HER2 chemotherapy combination and showed actual extension of survival in patients with brain metastasis and is FDA approved for this use. There are other compounds though that have activity defined as if you treat people with brain metastasis.
Some of those patients will have tumor shrinkage in the brain. And some of those patients will have extended survival with the medications. And so these include medicines like Neratinib, which is an oral pill, usually paired with Zeloda chemotherapy. T-DM1, otherwise known as Kadcyla, which is an IV medicine.
We don’t use Lapatanib so much anymore because we have Tucatinib and Neratinib, but it is around and in some countries where the other drugs are not available, it’s still used. We recently showed that by increasing the dose of Herceptin, just regular IV Herceptin, that we might see some additional activity. This is only a phase two trial. So I would not consider it the usual go-to, but it’s something that could be considered. There is actually also a phase two trial that has been presented for people with leptomeningeal disease, so cancer in the spinal fluid that you can actually safely give Herceptin or Trastuzumab directly into the spinal fluid.
That’s what intrathecal means or intraventricular through a special type of port that goes into the spinal fluid. It also has some activity and then, stay tuned, there’s a lot of questions about whether Enhertu has activity in the brain and there will be additional data presented this December at San Antonio.
So I think that’ll be interesting to see. There are some chemotherapies that work in the brain and so we can pair them with just regular IV Herceptin, and sometimes they do work. So for HER2, this is kind of the working list. And then there are on top of this, which I haven’t shown you are quite a number of clinical trials that allow people with brain metastasis. Some of them combine T-DM1 and Tucatinib or T-DM1 and Neratinib or Enhertu and Tucatinib, I mean, there’s all sorts of different combinations and there are new oral medicines that the hope is that they might be better even than Tucatinib or Neratinib. So I think there’s a lot going on there. For patients who have estrogen receptor positive or triple negative breast cancer.
There are drugs that have some reported activity, but the sort of strength of the evidence is not as strong, meaning that, rather than randomized trials or really very tightly controlled phase two trials. They might be more like a hospital team writing in and saying, we treated a certain number of patients with this medicine and look what we found.
So you can believe that there is some activity, but the strength of your certainty about being able to quote a chance of it working is not the same as we have for the HER2 drugs. But with that caveat, you know, there are drugs that work in the brain. And so we’ve seen things like Capecitabine or Xeloda chemotherapy work. On the right is a picture of actually somebody, we treated our institution who had a really dramatic response to her Xeloda.
This is not from radiation therapy. This is just from chemotherapy. Some of the platinum medicines can work. Some of the anthracyclines like Adriamycin or Doxil. And then there’s sort of like a mishmash of other miscellaneous medicines that we have seen some activity with in some patients.
So there are some options for people with estrogen receptor positive or triple negative breast cancer. But I would say that the options are overall a bit more limited. I think this is an area where we very much need better clinical trials.
I agree. When you’re speaking about clinical trials, why is it important for patients to participate or do you think it’s important for patients to participate? Is that something that you encourage your patients to do?
The way that I look at clinical trials is that there are multiple benefits to different types of people. And what I mean by that is that obviously sort of the reason that clinical trials are in place in the big picture is to understand whether medicines or different approaches are effective.
In hopes that if they are, they can be applied to a big population of people. So, whether it’s to try to get an approval for a drug or whether it’s to show a new standard of care, you know, that scientifically the reason a clinical trial is done. From a patient centered perspective, you know, in many cases, not all cases, but in many cases, a clinical trial could represent an interesting or good treatment option. Now, if we knew that the trial treatment was going to be better than all standard therapies, it wouldn’t be a trial anymore. It would just be approved therapy. So I can never promise to patients that the trial treatment is going to help them. But at the same time, I can’t actually promise that a non trial treatment is going to help.
I kind of think of a clinical trial as another option that can be weighed. Just like every option that you weigh you want to say, well, what do you think is your best guess as to whether it’s going to be effective or not? Not that we can be sure. The way that we might think about it is, well, does the target look good? What’s the preliminary data with the drug? Are you the first person in the world to get the drug versus the, you know, 500th person to get the drug? Because there are trials that span the whole continuum. Why do we think this medicine might work in people with brain metastases?
I try to share with my patients my personal feeling of whether I’m excited about a trial or not. I don’t ever make promises because you just can’t promise anything in breast cancer. And you just don’t know, we don’t have a crystal ball, but I think I think of it as really another option. I have a patient who enrolled on the HER2 Climb clinical trial with Tucatinib like four years ago, almost five years ago now. I take care of people who, you know, were on the original Abemaciclib clinical trials, like the phase one clinical trial. And they’re still on treatment now. I mean, it’s this fraction of patients. We have to be realistic, but at the same time, these are people who are alive and still on their trial treatment years later. I take care of somebody who now has been on immunotherapy for triple negative breast cancer with lung metastasis for six years.
She was on this medicine years before there was an FDA approval for any immunotherapy, for breast cancer. These are the kind of situations that give me hope and, you know, again, I, I really try very hard not to over promise, because you really don’t know. And for every person who does amazingly well, there are unfortunately people who don’t. But I think it’s one of the real treasures of working in the environment that I work in to be able to really see the difference that we can make.
Those are phenomenal stories. It’s important to have hope when you are in the situation like myself with brain mets or other patients who come to see you.
The one thing to note with clinical trials is that you’re going to receive, if you don’t go on the clinical trial, you’re going to receive the standard of care. It’s not like you’re going to receive, you know, a placebo or what some people refer to as a sugar pill if there are two arms to the trial. Is that the proper way to say it?
So you’re not going to get a treatment that’s no treatment. So for example, in the HER2 Climb trial, there was a placebo, but it was a placebo for Tucatinib and everyone got Herceptin and everyone got chemotherapy. So sometimes there are placebos, but they’re kind of like that. We don’t really have any trials in metastatic breast cancer that I’m aware of where it’s a treatment versus a placebo only treatment.
The other thing that’s important while talking about clinical trials is that, every drug that you take, that drug was once a clinical trial.
So it’s important. I think, just to recognize that when you’re on a clinical trial, often it’s the most exciting and new drug that could possibly be FDA approved. And what you would take if you didn’t go on clinical trial was once a clinical trial drug. And so it’s kind of a circle.
I think the science has really advanced. When I was a medical student -let’s just take the existing chemotherapies we have off the shelf and just give them the highest dose we possibly can. You know, there’s not a lot of science behind that other than these are the drugs we have. And if a little bit as bad is good, maybe a lot is better. I mean, that was literally, you know, how some clinical trials were done, because we didn’t have anything better. And now there are almost no trials that are just for breast cancer in general.
There are trials for HER2 and there trials for triple negative and trials for estrogen positive. And there’s so much science that goes behind the drugs that are in trials, and there’s a lot required by the FDA before a company’s allowed to test anything in people, you have to come in with a whole package of why scientifically you think your treatment is going to be effective.
Again, many things fail. I’m not saying that they don’t. But I think that the scientific basis behind the treatments that are being tested in the trials is so much stronger today, that it is a different experience going on a trial today than it was 30 years ago.
Oh yeah. That’s really interesting.
It’s not something I was aware of. Well, in speaking of clinical trials and having access to them I think they’re really important to participate in. So how does that work in terms of second opinions, because a lot of people are treated in places where there aren’t clinical trials and, and so do you feel that patients should get second opinions with brain mets?
You know, I think that if someone can do it, and there’s many logistical barriers that we still need to fix, I do think it’s a good idea if it’s possible. I think it’s because even if it’s not just for a clinical trial, it’s also partly for the ability to have an expert multidisciplinary team that can sort of weigh all the options and put them together with the patient. And I think that’s just something that’s really valuable in centers that specialize in people with brain metastasis that is beyond what trials they have on offer.
On top of that, you know, I think the existing way that people find out about trials. Which I know this organization is trying to fix, or at least contribute to an improvement in is fairly haphazard, right? Because, you know, if you go on clinical trials.gov, it has every trial, but it’s hard to really search for the one that fits you.
So it’s very complete, but it’s hard to sort of match with a trial with that website. Any one doctor is going to have a hard time knowing every trial that’s available in the U S like, I don’t know every trial that’s available in the U S. I think an advantage of going to a place that, you know, has a brain mets program, or if not a formal program, people who this is their interest is we all have our friends across the country and their informal networks.
And I know what studies are open at UCLA because I know my friend at UCLA has these studies open and I know it seems kind of crazy in 2021, that this is how we find out about different trials, but it is sort of how we found out about different trials. You know, I’m really hoping that the systematic effort that you’re so involved in is going to help that because I think not only do patients need help, but doctors, we need help as doctors.
And you know, when I see somebody who comes from far away, and is willing to fly anywhere in the country for a trial, I would really like to be able to honestly tell them I looked at all the trials that are available for you in the country. And this is the one I think you should go for. And right now there’s not a mechanism to do that.
There’s a lot of, sort of word of mouth and keeping tabs sort of thing. And again, I’m hoping that this effort that you are such an important part of is gonna make a difference.
Thank you. We will have a search engine or we do have a search engine on the website, and hopefully that process will be a little easier using that search engine.
And, we also have listed the places for second opinions that do have a comprehensive brain metastasis program. And while those are scattered across the US, we also list NCI centers, or where you can find NCI centers which are more likely to be offering clinical trials.
So hopefully if you’re looking for something like that, you can check that out on our website and hopefully it’s useful to doctors too.
So I think that, you know, sometimes patients can get in, you know, some people are very savvy and they’ll get right on the search engine and they’ll find the trials and they’ll sort them themselves. I mean, really, you are like super savvy Lianne. Right. You bring me trials that I might not have seen before and we look at them together. But, but I think the value of the website also is that, you know, if you’re a patient. You can ask your doctor to like add a visit, you know, you could ask your doctor to search it with you and they could give you their thoughts about which trials might be worth traveling for.
And so I think it can also help in a more collaborative fashion as well. Right now, if somebody asks me to do a clinicaltrials.gov search I don’t want to, you know, say bad things about them because the website is very good for many, many things. But if somebody came to me and said, I want to look for all trials for ER, positive metastatic breast cancer. Let’s see what there is on clinicaltrials.gov. It’s really not possible to navigate in a clinic visit. So I think that what you guys are doing is so important because if you get it down to like bite sized pieces, that really are focused on somebody’s specific problem, then it really becomes something that you can use as a tool with your doctors.And I think that that would actually be a great use of the tool.
We hope that patient’s doctors do use it that way together. And the clinical trials.gov has great features, but as someone who has used it, there are just thousands and thousands of trials listed and it can become very difficult looking at.
If you find the trial you want, then it’s great because you can see what the inclusion, you can see the exclusion, you look, you can look at the 174 locations the trial is open at. It works really well, but if you don’t know what you’re looking for, that’s when it becomes challenging.
Dr. Nancy Lin #5 – What is the Prognosis for Brain Mets?
So let’s talk about prognosis. It’s a challenging topic, but it’s important that we address it.
It’s a really challenging topic because it raises questions and thoughts that we don’t often like to think about. and also because there is a lot of variability in breast cancers. You know, if we look at someone with stage four pancreatic cancer there isn’t that much variability, unfortunately, you know?
And so when people are given a prognosis it’s not that different from one person to another. And I think one of the things that gives me hope about breast cancer, but it’s very hard with breast cancer is that there is a lot of variability. And there are people with brain mets who survive 10 years.
I take care of some people who are 10 years out with a diagnosis of brain mets and they’re doing very well. There are people who died within six months of the diagnosis of brain mets. And so when you give an average, you’re averaging those two sets of people and you know, it wasn’t very different to be thinking that you have less than six months versus you have 10 years.
And how do you communicate that with patients and how do you think about it as somebody who’s living with cancer in the brain? I think that’s really hard. The advice I do give to patients when you hear median survival or average survival or prognosis usually when people ask about prognosis, they’re asking about what’s the average survival. That’s how we answer the question. But it’s not a cliff list. So everyone thinks if you’re told six months, or you’ve been told two years, if you’re told whatever time that is, it feels like there’s a cliff and you’re going to get to that point and you’re going to fall off a cliff.
And unfortunately, some people don’t make it to the average. And a decent number of people make it beyond that because the way that we give our numbers is half the people don’t make it to that point and half the people make it beyond. Like 50% of people make it beyond the average that you’re being told. So I think again, that’s one of the tricky parts about breast cancer.
I do think that if you’re ready to hear about prognosis, it’s a good thing to ask your doctor. When you’re planning your life and the things that you want to prioritize and what you want to spend time doing, it is helpful to have some sense of what the range might be. And I think that might be a more useful way to think about it is, you know, what’s not the average, but what’s the range.
What’s the average scenario? What will be the best case scenario? What would be the worst case scenario? Unfortunately, there are people who I take care of and, and the best case scenario is a couple months. There are people who have really bad disease, but they’re also people I take care of where the best case scenario is years. I think if you are somebody who’s ready to hear that information, it’s a good thing to talk with your doctor about. If you don’t feel comfortable talking to your doctor sometimes, you know, you’ll work with a nurse practitioner or physician’s assistant, you could start with them first.
I think that over time, people are ready for different things too.
I agree that it definitely changes with time. Communicating to your doctor, how much information you want in order to be able to prepare or understanding that I’m preparing for this long, but expecting and hoping for this long. I think it’s important for patients to remember that it is an average and that what you just said is so spot on that, you’re averaging together very variable prognosis of life and, I try to tell people just in the end remember that you, you aren’t that statistic really no one is that statistic because it’s an average.
Where we become more accurate is when things really accelerate at the end. So when it comes down to someone having less than three months, are we perfectly accurate? No, of course not. I’m still surprised sometimes with how quickly things can go.
But, usually if somebody has less than three months, that we’re fairly accurate about. If a patient hasn’t brought it up proactively, I’ll start to, when things turn like that, I’m going to start to bring it up proactively. Cause I just think it’s important when people make decisions about next steps to weigh that.
But, you know, the reality is I’m not very good at predicting two years versus five years. Actually not at all. I think we just have to be honest about our limitations, about what we can predict and what we are not so sure about, especially as the treatments keep changing over time. Yeah. That’s something to consider.
From my own perspective, when I entered into the brain mets world, one of the drugs that helped me the most technically didn’t exist. So we were looking at averages without that drug and then for it to enter, it totally changed the game for me personally. And so you never know what’s coming up next and the research is moving in the right direction for those with brain Mets. So that kind of, kind of leads into being hopeful. And while nobody here, we, you, me is telling anybody to be, you know, positive or Pollyanna about this, because it’s very challenging, but there are cases of, I mean, I think it’s important to highlight some cases of hope and you have some of those to share I think.
I do. So I mean, I can tell you a few stories. I’m not going to tell any names. I’m not going to put some dates on it just to keep things confidential, but they are, these are real people. You know, there’s a person that I care for who was diagnosed actually now over 15 years ago with her brain mets and, received radiation treatment as was standard of care. And she’s like one of the lucky ones, like, I can’t explain why she has done the way she is. There’s nothing about her, or that’s different from many other people I take care of other than she has HER2 positive breast cancer, but now all these years later, she’s on Herceptin IV.
You know, and she’s had no progression of her cancer anywhere. It’s not like I had anything to do with it. It’s just we do see these people who have what we call exceptional responses and it doesn’t happen all the time. But it’s not like it’s one in a million either.
So I think for HER2, we are seeing people sometimes who live for years after a diagnosis. But, you know, I think this is where, how things evolve over time is something we can’t predict. So I couldn’t have predicted when she first had brain mets that nothing was going to happen in such a long time.
I wouldn’t have been surprised if something had happened. You know, a year into her brain mets diagnosis that we needed to treat again or wherever it is. So, but you know, again, if you ask pretty much any oncologist who takes care of breast cancer patients as their primary specialty, they’ll be able to name you people who are like this person.
I also know of a person with triple negative breast cancer, who, because she had so much disease actually in her liver and a little bit of disease in her brain. Her doctor decided to treat her with chemotherapy, and then deal with potential radiation to her brain after hopefully her liver responded to her chemo.
And when she had her repeat scans, actually both the cancer in her brain and her liver had gotten better. She actually stayed on that treatment for a period of time. I’m not saying that everybody’s like this, these are exceptional patients, but she had to come off treatment because of problems with her blood counts.
She was off of all treatment for two years, and that’s incredible. So again, these are not common situations, but I think that, and I want to be really careful not to, you know, over promise. But I do know from doing this for a long time, that people surprise me all the time and you Leanne, I mean, I don’t know how much you want to share about your story, but I mean, you know, certainly beyond the average survival and, and we’ve treated you with a variety of regimens, not all of which are necessarily the usual strategy.
I don’t mind sharing at all.
I think the frustrating part has always been like the location, right. Because if you’re, if your brain met had been anywhere else, like you would be even that much better. And, again, when I first met you, when your other doctors first met you, I mean, none of us would have promised that you would get to this point at all, but we would have told you that it’s not impossible that you could get it to get to this point. And then we see other people get to this point and you have, and I think that’s one of the most important parts about the research is like, you know, not to give up on, on patients and I don’t mean this in a way, like when it’s time, I am all for hospice. I’m very honest with patients and I will tell people when I think it’s time. I believe very strongly in honesty. But it’s also true that I think it’s important to share the patients who’ve done far better than we expected because they are not rare.
And because when we see patients like that, we know what’s possible. You can start to see what’s possible and you want it for more people.
Yeah. I mean, when I was first diagnosed, for those who are watching, I was diagnosed with brain mets only. So it was unusual and it was my first site and there was a number of them.
I think it was for those meeting me, you and other oncologists, you know, it didn’t necessarily look good from a standpoint of like she just finished early stages is now progressed to her brain and her brain only. But then here I am five years later. And while I prepared for a year, maybe two, I never let myself stop thinking that longer was possible. And, you know, I’ve fallen into that category of things being lucky or whatever you want to call it. But I think it’s important to remind yourself just that you aren’t a statistic and to take it day by day as best that you can.
I agree. And I think when you ask, when you talk to your doctor about your prognosis or when you go online and you research, which I do think is a good thing to do. I think there’s a lot of information you can get online. I’m not somebody who tells people like don’t go online. but I think that where your doctor can come in is saying for you specifically, what do they think? Because you know, your doctor knows what treatments you’ve gotten before. How many spots are in your brain, where they’re located. What the pace has been. There’s like all these factors that really are not captured in the average, it’s just everybody. When you’re talking about prognosis, I do think it’s important to ask your doctor, like for me specifically, what do you think?
And you know, that you’re not going to be able to have a crystal ball and you know, it’s not going to be perfect. And you might ask for range rather than like, this is the average, but I think it’s totally fair to ask, have you seen people go longer than that? You know, I think that’s a totally fair question. And if you’re ready to hear the answer to that question.
To me it’s so important to have an open dialogue with your doctor throughout all of your metastatic treatment, regardless of whether it’s about prognosis so they know where you’re at and what kind of information you want.