S03 EP17 MBC101 “What happens when MBC spreads to the brain?”
[00:00:00] Musa Mayer: I haven’t been involved in advocacy since 2015. And so hearing these advances because during the years that I was working, there were really only two significant changes in treatment. And one was that women were no longer being given whole brain radiation, just as a matter of course, targeted. Focused radiation became much more standard.
And the other change we saw, which was subtle, it was very difficult to find trials for metastatic patients that did not exclude any patient with a history of brain metastasis, whether or not had had been resolved. But by the time that I retired, that was far more common. And you may notice how many more listings there were in the later years.
And I agree with about active brain mets and leptomeningeal disease. We need more of these trials that are broadly appealing to patients and that are not so selective for sure. It’s the most frightening aspect of the most frightening disease.
[00:01:25] Lisa Laudico: welcome to the our MBC life podcast from share cancer support, dedicated to exploring life with metastatic breast cancer. From the perspective of us that people living with this disease. And the experts who partner with us to help make our lives better. I’m Lisa Laudico and I’m so glad you’re here since no one should face MBC alone.
[00:01:46] Victoria: Hello, friends I’m Victoria Goldberg. As you know, our MBC life is taking a little break and the fourth season will not launch until March the second. So you may be surprised to see the brand new episodes of this podcast. Well, these episodes are our special way to celebrate and mark the launch of a new website that was created by the metastatic breast cancer patient advocates.
For those in our community who are living with CNS metastasis, commonly known as brain mets last week, the host Lisa Laudico spoke with the architects of this incredible website, Christine Hodgdon and Leanne Kramer and legendary Musa Mayer. This website was inspired in part by the work that Musa did in the early two thousands.
It was an extraordinary interview and I urge you to listen to it if you haven’t already done so. And by the way, you just heard Musa’s voice at the open of this episode, discussing the changes in the treatment of brain Mets in the last 20 years. So. We’re doing something different on October 12th, 2021, Leanne Kramer and Cher hosted two brilliant young clinicians from Moffitt cancer center in the discussion on management of breast cancer, brain metastasis.
This podcast is a slightly edited audio of the webinar and the Q and a session at the end. I will let you in on a little secret, there is two compelling reasons for releasing this webinar. The first one is obvious to you, and it will be obvious as soon as you listen to it. It’s very good. And it’s very, very informative.
The second reason is to give you a glimpse into how we envision our next seasons road to a cure. Our conversation will continue on changed intimate conversation with the leading experts during the cutting edge research, into the science of breast cancer. But in addition, we would like to include more content with an education on it for the newly diagnosed or those who simply want to dip their toes into way their science order, which tends to simply call this content MBC 101.
Today’s episode is an example of what we have in mind and we call it out first MBC 101 on brain Mets.
So what are the brain metastases or more correctly? CNS metastases from breast cancer. They’re the second most common cause of central nervous system metastases, about 10 to 15% of women with stage four breast cancer. Developed brain metastases for most the breast cancer has already traveled to another part of the body, such as the bones liver, or lung.
However for about 17% of women in this group, the brain is the only site of metastasis brain metastasis can present as a single tumor or multiple tumors. This rate is as high as 25 to 50% for people with triple negative breast cancer and even higher 30 to 50%. In her two positive disease and 14% in hormone receptor positive.
So here is Lianne Kramer. Introducing our guests.
[00:05:46] Lianne Kraemer: Welcome to the webinar of management of brain metastasis. I’m Leanne Kramer. I’m a patient advocate. I’d like to introduce our speaker. Dr Aixa Soyano is an assistant member in the department of breast oncology at the H Lee Moffitt cancer center and an assistant professor at the university of south Florida.
Dr. Soyano originally from Venezuela and received her MD degree from the Luis ZTE school of medicine. The central university of Venezuela, she joined Moffitt cancer center to focus on breast cancer treatment and research. Her research interest is in the future of oncology related to personalized medicine.
And then we also have Dr. Cameron Ahmed he’s an assistant member of the department of radiation oncology and department of immunology at Moffitt cancer center. He is also an assistant professor in the department of oncologic sciences at the university of south Florida. Dr. Ahmed received his medical degree from Mayo’s clinic school of medicine in Rochester, Minnesota, and completed his radiation oncology residency at Moffitt cancer center. Dr. Ahmed’s clinical focus is on the management of breast cancer. Dr. Ahmed’s primary research interest is in studying the synergy between combinations of immunologic and targeted agents with radiation therapy to improve clinical outcomes.
He is the principal investigator of several multi-center. Clinical trials and the management of advanced disease and brain metastasis with novel therapeutic and radiation therapy. And with that, I am going to turn it over to our speakers.
[00:07:36] Victoria: In the next segment, you will hear Dr. Ahmed who is a radiation oncologist, explain how the brain metastases developed and there is. But local radiation therapies and ongoing clinical trials at Moffitt and other cancer centers are the main subject of his presentation. So here is Dr. Ahmed
[00:07:58] Dr Ahmed: Thank you so much for having us as was mentioned, I’m a radiation oncologist at Moffitt cancer center. I’ve a clinical and research interest in the study of breast cancer brain metastasis.
I’m going to be speaking first and giving information about the local therapies for brain metastasis, brain metastasis. What are the risk factors for the development of brain metastasis from breast cancer, but it’s believed that all brain metasteses initially develop from the primary tumor site. The most common primary tumors that develop brain metastasis include breast cancer, lung cancer, and melanoma.
From the primary tumor cells, enter the bloodstream and then can get arrested in the capillary beds of the blood-brain barrier. And then from here slowly, enter the brain vasculature with the assistance of certain genes and proteins, the risk factors for the development of brain metastasis from breast cancer, advanced stage at diagnosis, certain breast cancer, subtypes such as her two positive or a triple negative.
Preferentially develop brain metastasis. And then also patients who have the BRACA one, two gene mutations may also be at higher risk for development of brain metastasis. There’s other clinical factors that may also contribute to an increased risk. This includes a younger age, the development of pulmonary or lung metastasis, and then also African-American ancestry.
So because of the blood-brain barrier, which limits the ability. Traditional chemotherapeutics and targeted agents from entering the brain. Local treatments have really been keys to the management of brain metastasis. It is believed that ionizing radiation treatment can kill cancer cells by causing DNA damage.
This can lead to chromosomal damage such as the dicentric green formations of chromosomes that preferentially have the ability to kill cancer cells while allowing normal cells to regenerate. And so for patients who have. More isolated brain metastasis and patients who are symptomatic from larger brain metastasis surgery is recommended for removal of that brain metastasis and for potential diagnosis of.
There’s been a few important studies, which have shown us that delivering radiation treatment to the tumor cavity following surgery is really now the standard, or this includes one phase three study, which showed that there was improved cognitive function with the delivery of SRS compared to whole brain radiation treatment, which is what we used to do years ago.
And then another phase three study has also revealed that this reduces the risk of local recurrence in patients that have 1, 2, 3 surgically removed brain metastasis, compared to observation for patients who have a few lesions that are identifiable by MRI. Stereotactic radiation treatment or focal radiation treatment just recommended for patients who have more diffused brain metastasis.
This doesn’t necessarily mean five, but certainly patients who have more than 15 brain metastasis, whole brain radiation treatment is. Recommended over stereotactic radiation treatment, because in addition to the lesions that we might be able to identify on an MRI. There may also be a micro metastatic deposits that could lead to better outcomes with whole brain radiation treatment.
The radiation. Planning process is generally the same for most patients. Initially, all patients will undergo a simulation scan. This could be done either with a CT or with an MRI. And then from this scan, the radiation oncologist plans out the delivery of the radiation treatment. This planning process can take a few days to a couple of weeks, depending on how complicated a radiation treatment plan is being created.
There’s always a verification process that takes place from the planning stage to make sure that what has been designed by the radiation oncologist, alongside their radiation treatment planners and the physics team can actually be delivered on the machine. I mentioned the two different approaches that we use in terms of radiation to treat brain metastasis, whole brain radiation with radiation dose, that’s going throughout the brain is typically delivered over one to two weeks.
And generally these are lower doses than what we’re using. When treating with the stereotactic radiation stereotactic radiation treatment is a higher dose radiation treatment. That’s just focused in on the tumor that we can identify on an MRI. And this is delivered typically over one day, but for larger brain metastasis or following surgery, this may be delivered between three to five days.
So what are the side effects of brain radiation treatment? Every patient is a little bit different, but generally for all patients in the short term, this could include fatigue. It could include scalp irritation or hair loss, which may or may not be permanent. There might be nausea or vomiting, headaches as well as multiple hearing.
It’s important to note that a lot of these side effects can be managed fairly easily by your radiation oncologist. If you have these side effects at all, uh, long-term side effects from radiation treatment, um, includes short term memory loss and the damage to normal tissue. That’s a rare side effect of.
Uh, radiation treatment. One of the reasons why we like to use stereotactic radiation treatment over whole brain radiation treatment is because of the potential for short term memory loss that can occur from whole brain radiation treatment. There have been studies that have looked at different techniques to minimize that side, or one of these techniques is to avoid.
Treating the hippocampus during the delivery of the whole brain radiation treatment, the hippocampus, which is located in the temporal lobe of the brain has important functions in the development of memory. And by avoiding doses of radiation treatment there, we can decrease the effect on executive function and then.
In addition to that, we will prescribe a man team, which is a GABAA receptor antagonist, given to patients who have dementia delivering this alongside the radiation treatment during, and then up to six months afterwards has also been shown to be beneficial in reducing the effects to memory from whole brain radiation treatment factors that have been shown to.
Predict overall outcomes and patients that have brain metastasis and were found to be performance status, breast cancer, subtype age. So patients who are older may have potentially a worse outcome or more brain metastasis as well to an older study. This was published in 2015, found a range of survival between three to 26 months.
And since that time. It’s been a lot of new improvements in the management of brain metastasis, both in radiation treatment and in systemic management. But I think some of these factors still go into play in determining overall prognosis. So what is the impact of standard brain metastasis management? A couple of studies have shown that we might be able to get over the barrier of that limits.
Our ability to combine radiation treatment and a systemic therapy. If we can sequence delivery of radiation in the window of about one month in which we can limit the role of the blood-brain barrier in inhibiting the entry of a systemic agent, and then allowing that agent to potentially act in the brain because of that, there’s been a studies that we’ve opened at Moffitt cancer center to help see whether or not we can potentially take advantage of that. Immunotherapy has had a large role in the management of other cancers, melanoma non-small cell, lung cancer, and now also has an increasing role in the management of breast cancer. So we were interested in looking in the setting of breast cancer brain metastasis, to see if there’s a window that we could use to deliver the.
Um, immunotherapy with the radiation treatment to allow for an improved outcome. The smallest study that we did with 12 patients found that the treatment was safe and potentially this might be an option for triple negative patients. And we’re going to be continuing to study this at Moffitt cancer seven in an upcoming trial.
And I just wanted to briefly touch on leptomeningeal disease and a potential treatment that we have for patients. This type of cancer, leptomeningeal disease is a more advanced form of central nervous system metastasis. It’s believed to involve the lining of the brain and the fluid that surrounds the brain and the spinal cord for patients who have her two positive leptomeningeal disease.
It’s been shown that if we can deliver a, her two targeted therapy directly into the cerebral spinal fluid, through an Ommaya reservoir, we might be able to lead to improved outcomes. They study published in 2018, showed us that using intravesical Herceptin with the delivery through an Ommaya reservoir may have a benefit for patients that have her two positive disease.
And now at Moffitt cancer center, we have opened a subsequent trial where we’re delivering intrathecal Herceptin alongside intravenous. Or choose a map as well for patients that have her two positive leptomeningeal disease, radiation treatment plays a large role in patients with leptomeningeal disease by palliating symptoms.
[00:17:35] Victoria: With this Dr. Ahmed concluded his presentation and I hope you noted an interesting discussion about two new approaches in trading CNS Mets. The first one is skip a compass bearing whole brain radiation. She put compost sparing, whole brain radiation was supported by insights into the unexpected source. Taxi drivers in London back in 2010 research has discovered that a part of the brain called the hippocampus was larger in London, taxi drivers, then other adults who didn’t drive taxis, this part of the brain has been shown to be critical in new memory formation and learning research has attributed the growth to the years of grueling training that taxi drivers endure to memorize some.
5,000 streets and thousands of landmarks. The study provided one example that the dowel brains or more versatile than previously. Oh, the research had also supported the theory that neural stem cells located in the hippocampus play a major role in adult learning and memory stem cells located in the hippocampus.
Uh, some of the most sensitive in the brain to radiation with hippocampus theory doctors can use advanced technologies to shield the hippocampus from radiation beams while still treating the rest of the. brain. Time. I had also talked about intrathecal trastuzumab and now produce a map in the management of her two positive leptomeningeal disease I’ll bring and spinal cord are protected by three layers of tissue called meninges between two of the layers is cerebral spinal fluid or CSF.
In a place called the intrathecal space. That’s why cancer fighting drugs placed into the are called intrathecal chemo drugs, or it. One way to get this treatment is with lumbar puncture or spinal tap. Herceptin of course, is given over a long period and many doses lumbar puncture just does not cut it.
So different delivery mechanism is generally used. This is a small bill shaped device called an Ommaya reservoir. It’s placed on the patient’s called during the short surgery it has a catheter that connects to intrathecal space, getting treatment this way is like getting it through an IV port, the elsewhere in the body.
And next is doctor. Aixa Soyano
[00:20:22] Dr. Aixa Soyano: thanks for having me today. And I’m gonna talk to you guys a little bit about the systemic therapies for breast cancer, brain metastasis. We know that not all breast cancers are the same, not all breast cancers are developed or found because of the same cancer markers.
So we tend to divide them into different subtypes. And those subtypes are based on the three main receptors that we can find in breast cancers, which are the estrogen receptor progesterone receptor and the her two receptor. So when either the estrogen or the progesterone is. Overexpressed in breast cancer, we call that hormone positive breast cancer.
And what that means is that the breast cancer cells are feeding off of the hormones, estrogen, or progesterone that’s around in our bodies. So they use them as a food or fuel to live. The her two receptors, a different receptor when it’s overexpressed it just allows the breast cancer cells to grow rapidly. So the most common subtype of breast cancer in the U S is hormone positive her two negative and represents about a 70% of those breast cancer cases.
The other third is represented the, between the triple negative and the hormone positive. And there’s. Uh, uh, different molecular subtyping, it’s called luminol AB basal like in her two there’s a lot of overlap, but it tells us mainly that for those hormonal positives, there are ones that have a little bit better from gnosis and responsiveness to hormonal treatments and other ones that are less responsive to hormonal treatments, but responsive to chemo.
It allows us to determine what’s the right treatment for each subtype of breast cancer. So back to breast cancer, brain metastases’ is how common is it? We know that as patients are living longer and breast cancer is a second most common cancer in the U S and females after skin cancers. And we’re detecting it earlier.
The incidents of. Brain metastases seems to be going up as well. A meta analysis. It means a collection of other trials that was published this year. It showed that the incidence of brain metastasis at, or following the diagnosis of metastatic breast cancer ranges between 25 and 46%. So somewhere along the 20 to 40% of breast cancer patients that have metastasis will develop.
Um, metastasis to the brain. We also know that the hormone positive her two negative was the most common subtype of breast cancer found in early stage. But this is not true for breast cancer, brain metastasis in brain metastasis. The most common ones are the, her two positive and the triple negatives. And that represents a little bit over a third of those.
And then only about 15% of the breast cancer brain metastases are hormone positive, her two negative. Here at our institution, we did a retrospective review of all the. Brain metastases that were found in our database of breast cancer, lung cancer melanoma. And we found that because there’s no real screening national guidelines looking for brain metastasis in breast cancer patients, the patients that had breast cancer were more likely to be younger with more advanced.
Central nervous system disease require whole brain radiation and have poor overall survival in general, compared to the lung cancer patients and the melanoma patients. So it’s food for thought about modifying and trying to find this patients earlier so that their outcome can be improved in the future.
But why is it so challenging to treat and how is it that it’s so common? So. Dr. Ahmed already talked a little bit about the blood brain barrier. So we know that it’s a network of vessels and tissue that keeps the space very close, so that harmful substances can not penetrate the brain cause the brain is our most vital organs.
We don’t want any harmful substances or toxins or bacteria or viruses to get into that space. However, in patients that have brain metastases, as we mentioned before, sometimes when we do radiation, we open a space into the blood brain barrier and some of those drugs can actually penetrate and that will help the brain metastasis treat.
So, um, hormone positive hormone and negative breast cancer. As we said, as the most common
type of breast cancer, it tends to be more indolent and the patients tend to have a longer life expectancy. Common sites of metastases include the bones, the lungs, and the liver and initial treatment options include endocrine therapy, which we call it hormone blockers plus or minus targeted therapy, which could be CDK four, six inhibitors or mTOR inhibitors.
This are inhibitors of. Particular, um, areas of the cell cycle. So if we are inhibiting division of the cells, the cells get arrested and they cannot figure progress. Some common CDK, four, six inhibitors are the rents are palbociclib or Abemaciclib on Kisqali or Ribo side clip. Why is that important?
Because we know that, um, CDK four, six inhibitors, especially Pablociclib and Abemaciclib cyclists have shown some intracranial activity in small, early phase trials. So it gives us an idea that this drugs potentially compensatory the blood-brain barrier and help treat the brain metastasis. In combination with a local regional therapies, there was also a phase two trial of hormone, positive metastatic patients with active brain metastases that showed a modest clinical benefit in this patient.
So this is a small trial, and even though they did not meet what we call their primary endpoint. It included a variety of patients. So included pieces that were not resectable, meaning they couldn’t go to surgery as a, had the more advanced CNS disease called leptomeningeal disease and patients that were actually planning to have surgery.
But importantly, the blood study said from the patients from this trial showed that there were adequate concentrations of the drug of Abemaciclib and the brain metastases that suggests that there was a good penetrance of this drug. So that led us to study that here at Moffitt cancer center, Dr. Ahmed being the PI.
So we have a phase one, . Two study of stereotactic radiation or SRS, and the management of patients that are hormone positive, her two negative with brain metastasis. So this trial allows patients that are eligible for SRS. That have up to 15 brain mets and they will give them, and most likely along with radiation and they will continue their, uh, other Abemaciclib’ and interpret therapy.
And we will examine what’s a follow-up and their response. So the trial that we just talked about was open here at the Moffitt cancer center. But additionally, at Emory university in Atlanta, there’s a similar study using stereotactic radio surgery with Abemaciclib or Palbociclib and treating this patient. So another investigator is looking at that same concept.
Hopefully we’ll have more data so we can change practice for the future. A different subtype of breast cancer is called triple negative. And what that means is that lacks expression of estrogen progesterone or the, her two receptor. This cancers tend to be more aggressive and are associated with genetic mutations or predisposition, such as Brock on mutations, probably two mutations among others.
And this patients are commonly treated with chemotherapy. Plus, or minus a combination with immuno therapy. The most common site of metastasis are liver lung’ and brain. And because we treat this patients commonly with chemotherapy, we know from experience that some chemotherapy agents penetrate the blood brain barrier to some degree.
And as I mentioned before, there’s probably more. Permeability after local treatments, allowing more of this drug to penetrate that space. Some of these drugs are the flouro result, derivatives, such as , um, some platinum cells. So carboplatin, cisplatin, and some anthrocyclin such as doxorubicin, which we all know as the red devil, unfortunately.
In addition, there was a recent approval last year in April by the FDA. So it’s an antibody drug conjugate called sacituzumab govitecan . The brand name is . Trodelvy I’m an antibody drug conjugate. It’s an antibody that goes in and targets a specific protein present in cancer cells. For this particular drug, the protein is called trope 2
and that antibody is linked to a small chemotherapy drug. That drug is called SN 38. So when the medication is administered, so it’s an IB medication and said administered. It goes to targets the trope to proteins in the breast cancer cells and delivers the chemotherapy S in 38 directly into the cells.
And that inhibits the repair of DNA. To cell death. This was based on results from a trial called the EMU 1 32 trial. And that led to the approval by the FDA, but there was another child called the ascent three that showed that in some patients that have. Breast cancer brain metastases. There wasn’t improvement in the progression-free survival or the time to progression in patients that had stable brain metastasis from their tumors.
Another type of breast cancer is called the, her two positive breast cancer. And that’s characterized by. Overexpression of the human epidermal receptor to, we call that her two. So in a normal breast cancer cell, if they have a normal amount of her two receptors that sends some signals telling the cells to grow and divide.
But if this is overexpressed, then there’s too much hard to signaling and then the cells keep growing and growing and grow. This is considered an aggressive type of breast cancer. However, breakthrough research in this subtype has completely changed prognosis to good, and there has been multiple new treatments approved in the past five years and some have blood-brain barrier penetrance.
It was 1984, where the hard to gene was initially identified. And in 1985, gene amplification was found in breast cancer cells. So it took a few years to develop this drug, this monoclonal antibody called Herceptin. That was developed in 92. And then in 98, it was approved for the treatment of metastatic her two positive breast cancers.
And in 2005, it was shown that it improved the life of early her two positive breast cancers. Then it took a few years, but in another drug called a pop-in him also. Was approved for the treatment of metastatic her two positive breast cancer. And after that, it was just an explosion of treatment options for this patient.
So in 2012, we got the approval for Pertuzumab, another monoclonal antibody that targets that her two proteins in 2013, TD, and one another, um, antibody, drug conjugate that targets the same protein. And then just in the past two, three years, we’ve gotten multiple indications and multiple treatment options for this patient.
So more to come in this subtype of breast cancer. trastuzumab emtansine or the brand named Kadcyla is an antibody drug conjugate that targets the her two proteins, but then it . Delivers a small chemotherapy payload to the cells. It was approved in 2013 by the FDA for the treatment of metastatic her two positive breast cancer, based on the Emilia trial, that particular trial randomized patients to receive the TDM one.
Versus Lapatanib, which is another hurted drug in combination with Cape Cytovene, which is a chemotherapy drug. And that was a standard of care at that time. And this particular trial showed that there was improvement in the survival of this patients. And then the time to progression for this patients a few years later, the investigators went back and looked for patients that were enrolled in this trial.
That already had a history of stable brain metastases. And they saw they had about 50 patients that each are, and they noted that the patients that received TDM one actually had an improvement in their survival. So they were living longer by receiving TDM one. Then it keeps that . So that translates into possible CNS activity of this drugs into the brain metastasis.
Her to climb was another trial that compare the use of Tucatinib, which is an oral drug that blocks various sites of the her two family of proteins. Plus Cyclophosphamide which is a chemotherapy drug plus Herceptin in comparison to Herceptin Cyclophosphamide and placebo. This had a pivotal trial design in the sense that this particular trial allowed patients that had active brain metastases to be enrolled and receive the experimental treatment.
And when we look at clinical trials in general, most patients that have active or progressing brain metastases are excluded from the trials. So this particular trial allowed patients to participate. Of the total 612 patients, 291 had brain metastases. So 48% of the population had brain metastasis. 40% of those had stable brain Mets, whether they had treated, they didn’t need any new treatment.
And then 60% had active brain metastases. 20% of them were just diagnosed with newly brain mets and some had had a diagnosis of brain metastasis were treated, but were progressing. And then the recent. the drug We know that the combination of the Tucatinib interest to up and Cyclophosphamide reduced, the risk of disease, progression, or death in patients with brain metastasis by about 52% when they studied all the patients that received that Tucatinib, not only had an improvement in disease progression, but it also reduced the risk of developing future brain lesions or even death.
So this completely changed. Um, the way we see her two breast cancer, brain metastases, because we know that we have drugs that actually can penetrate that space and can benefit patients to help live longer. Another antibody drug conjugate that was approved in 2020 was in her two or fam trust to some of their CDN.
This was approved after a phase two. Trial called the destiny breast. Oh one. This is a treatment that proof for metastatic breast cancer patients. So this is also. Proven to be beneficial in patients in the earlier metastatic setting with just a few lines of treatment in this particular trial patients were heavily pretreated, so there’s more to come and this is being studied in patients.
Um, brain metastases, only other oral combinations that we sometimes consider in her two positive breast cancer patients that have brain Mets is the combination of Cape side have been the chemotherapy drug plus neurotic or Lapatanib, which are oral drugs that target the heart tube proteins. And they have also shown to be beneficial in this particular subtype of patients
[00:36:06] Victoria: in the next section Dr. Soyano lists. Trials for Her2 positive and triple negative cancers. And I decided to keep it in, but don’t bother to take the notes and just look it up in our episode notes and you will find them there.
[00:36:27] Dr. Aixa Soyano: So some clinical trials and triple negative and her two positive brain metastases. The first one is an antibody drug conjugate. Tridevi that’s being used in her two negative breast cancer with brain metastases. It’s a phase two trial and it’s across the USA. So it’s just about a matter of looking what sites are open and see if a patient might participate.
Another trial, a phase one B2 trial called Topaz. It’s looking at Tucatinib in combination with pembrolizumab, which is an immunotherapy drug and trust to use amounts of the traditional Herceptin and, uh, her two positive breast cancer brain metastases. And that’s in Cedars-Sinai medical center in LA there’s another child based off the NIH, looking at TDM one alone versus TDM one chemotherapy drug called.
Temozolomide in secondary provision of her two positive breast cancer brain metastasis. There is another experimental drug called GDC Cirrus 0 8, 4. And that’s available at Dana-Farber for patients with her two positive breast cancer brain metastasis. There is another mechanism of escape or resistance of this treatments through the, her three protein and here at Moffitt at Roswell park, we are studying the use of vaccine.
So vaccines have a type of white blood cell club and dread excels that. We’ll target this, her to her three, um, proteins. And we’re going to combine that with pembrolizumab immunotherapy drug for the treatment of brain metastases from triple negative or her two positive breast cancers. So this is a phase two is actually open at Russell Park and it’s about to be opening at Moffitt.
The next study is a study of T. D. So that’s, uh, in her too, um, that we talked about, and this is being studied in a phase three in multiple sites across the United States and internationally for patients who have metastatic her two positive breast cancer with, or without brain metastasis. So again, there’s trying to expand to see if this drug is beneficial in this particular set of patients.
And then there’s also a study based of city of hope that is looking at car T cell. So it’s a type of engineer immunotherapy of our patients with recurring brain or leptomeningeal disease. So in conclusion, breast cancer, brain metastasis incidents is increasing didn’t prove systemic control as well as improved imaging techniques.
Multidisciplinary management is important to tackle. The brain ends systemically stereotactic radiation is the standard of care for localized disease. Whole brain radiation is used for more diffused brain metastases and improve outcomes may be achieved with combined local and systemic approaches. So that was our presentation for today.
Thanks for joining us. And now we’re going to go with some questions.
[00:39:45] Lianne Kraemer: Thank you so much, Dr. Soyano you mentioned at the beginning of your presentation that there’s really not a guideline for screening for brain metastasis. Can you speak a little bit to why that is like that? And whether there should be,
[00:39:59] Dr. Aixa Soyano: yeah, we go by the ASCO national guidelines or the NCCN guidelines and there is really no.
Um, guidelines for screening, meaning when a patient is diagnosed with metastatic disease and we do systemic scans, every, let’s say three or four months or every six months to see what’s the benefit of treatment. And if the cancer is responding to the treatment or not, when someone is diagnosed, for example, with lung cancer, we know that because there’s a really high incidents of.
Possible metastasis to the brain. The guidelines recommend a screening MRI or CT of the head in breast cancer, because a incidence is not as high. It’s not really adopted by the national guidelines, but we find the patients that have breast cancer have more advanced disease in their CNS because we detect them once they have.
We’re looking into our own data and we are going to publish that data. And we hope that this gets reconsidered by the national guidelines. I know there are other institutions that sometimes have institutional guidelines where they would say, yes, we’re screening all pieces with high risk. Let’s say young patients are her two positive or triple negative.
So I think it’s just looking into what the trend is right now, in order for us to modify the guidelines for a future.
[00:41:17] Lianne Kraemer: So then it must be symptoms that lead to you looking into other brain metastasis exists. Can you talk to the symptoms that are present or can we present with brain metastasis as well as leptomeningeal disease there’s some overlap or what leads you to then do screen?
[00:41:36] Dr. Aixa Soyano: Yeah, absolutely. It’s hard in the sense that we could all have a headache and that not necessarily might mean that someone has some metastasis to their brain. There is overlap into the traditional tumors, into the brain and the CNS leptomeningeal disease. Typically when I counsel my patients, I talk to them about symptoms that are not their usual.
So if they had a history of headaches, they’re having a new headache, a different headache, a headache that’s associated with other symptoms, such as changes in their mission or nausea or vomiting or. The headache wakes them up in the middle of the night, or they wake up with nausea or vomiting. Those tend to make me a little bit more suspicious that something might happen in the brain.
And I want them to bring that up to my attention so we can do the appropriate workup. Also when patients have sudden loss of vision or the something that’s associated with weakness, such as like when patients have a stroke. Right? Cause it depends on what part of the brain is a tumor located at. And if.
Swelling that can cost compression into the other structures that might bring symptoms. That’s when we can have loss of balance, we can have weakness. We can have difficulty speaking. We can have peripheral or. Central vision loss. So there’s just a range of symptoms that we try to cancel our patients to look for.
And then there can be some overlap, into leptomeningeal disease, but leptomeningeal disease tends to cost more of a diffuse, sudden drop and sudden change in their neurological status. And those symptoms tend to be progressive, like. Worsening more rapidly than with a traditional brain tumor. So if someone is having some back pain and the back pain suddenly starts feeling that they have no sensation or they start having loss of control of their bowel or bladder.
And that tends to speak a little bit more about leptomeningeal disease, but some patients can also be asymptomatic. So that’s why there is really challenging.
[00:43:44] Lianne Kraemer: Yeah, it is very challenging. As you mentioned, there are so many more trials for her, two positives and triple negative, or ER, positive, especially with triple negative, which makes up almost half a brain mets.
Why is this? And how do we encourage researchers to work more on this aggressive subtype and open more trial?
[00:44:04] Dr. Aixa Soyano: Yeah. And that’s an excellent question. The breakthrough of newer therapies have been developing her two positive breast cancer for the past 20 years. So I think that’s why they’re in many more trials because we have so many options, but that doesn’t mean that there is no clinical trials looking at triple negative.
It’s just has been a little bit harder to tackle and more recently, but there are many skate mechanisms for the triple negative. And I think it’s just a matter of time that new clinical trials pop up in the future for this subtype of breast cancer.
[00:44:34] Lianne Kraemer: Okay. Is there such a thing as a best systemic treatment for each subtype of breast cancer for brain metastasis?
For example, this is the best for her too.
[00:44:46] Dr. Aixa Soyano: Yeah, I don’t think we have any data right now comparing each approach to another approach. So there’s no good data to say, oh, this is the best treatment. It’s a discussion of oncologists with the patient and see how patients are tolerating the treatment and their past experience with other drugs.
There’s a lot of discussion into why would I choose a regimen over another? But sometimes even though the best treatment might be this, I know that my patient’s not going to tolerate it. So it’s also about quality of life and maintaining that quality of life. So there’s a lot of thought that we put into it, but we also have to consider all the patient characteristic in that relationship with the patient.
So it’s about exposure to different groups.
[00:45:33] Lianne Kraemer: So once you have treated brain metastasis, especially from a radiation perspective, is there a protocol for monitoring the brain after treatment? And if so, what does that look like?
[00:45:45] Dr Ahmed: We reorder an MRIs pretty regularly after the diagnosis of brain metastasis.
Usually it’s about every two to three months for the first year. And then potentially if we have good control and we can space that out a little bit more. But basically we don’t really like to go beyond maybe four or five months without having some sort of image that’s taken because the old end, after the detection of brain metastasis date, if there are future, bring the task list to catch them early so that they can.
[00:46:18] Lianne Kraemer: So once you had brain mets you will always be monitored for them. Is that what I’m hearing? You’re saying?
[00:46:24] Dr Ahmed: Yeah, that’s certainly, I think our practice here once there is a diagnosis of brain metastasis that monitoring with MRIs does continue.
[00:46:32] Lianne Kraemer: Okay. And, um, Is there a best imaging tool? You talked about scanning or imaging looking at the brain after treatment.
What imaging tool do you use is considered the best practice?
[00:46:47] Dr Ahmed: So the standard would be to do MRIs that offers a better resolution than a CT scan would and allows for the detection of smaller brain metastasis that could be treated when they’re asymptomatic.
[00:47:00] Lianne Kraemer: Gotcha. I don’t think this is something that was addressed during the presentation, but it’s certainly a popular, um, conversation among those who have brain metastasis and get radiation.
Is that a radiation necrosis? What are the risks for it? And how do you, I know there’s some difficulty in distinguishing tumor growth versus radiation necrosis. If you could just speak to that a little, that would be.
[00:47:26] Dr Ahmed: Yeah, that’s a good question. The factors that can, um, lead to higher risks of radiation, necrosis potentially are the treatment of larger brain metastasis, higher doses of radiation treatment as well, and the treatment of multiple brain metastasis as well.
So the question of. How we can distinguish between radiation process versus pseudoprogression or radiation treatment changes after patients have received radiation treatment versus tumor growth and subsequent scans after radiation treatment. So typically the reason why we’re also ordering these scans at regular interval is to really monitor the changes after radiation treatment.
Sometimes it’s hard just with one scan. What exactly is occurring. And certainly a patients are asymptomatic. What our preferred approach would be is just to follow those because more than likely what’s occurring is probably just radiation treatment changes. When symptoms also occur alongside those changes on MRI, the radiation oncologist might place patients on steroids and then really it’s dependent on where we treated a discussion between.
The neurosurgeons as to whether or not we feel like it might be beneficial to remove that you’re new, that’s been radiated because really the only gold standard to determine whether or not it’s radiation, necrosis versus potential tumor growth would be to remove the tumor. But obviously that carries risks.
It’s really a discussion between us, the neurosurgeons. Also the radiologists play a large role in this there’s something. Additional scans that we can get profusion MRIs, um, that offer a different level of resolution that can help us answer these questions. If that makes sense.
[00:49:14] Lianne Kraemer: So it sounds like while other imaging exists, like I’ve heard people talk about MRI spectroscopy and that sort of thing.
What you’re saying that really is the best judgment of the clinician over time to watch what the tumor does versus relying on any kind of imaging tool to say yes or no. This is a diagnosis,
[00:49:34] Dr Ahmed: correct. Yeah. The management strategy we follow over here is when there are cases where we’re concerned about one of those events or more than others, really to discuss those cases in a tumor board setting and to have all the experts weigh in on that question.
[00:49:49] Lianne Kraemer: Gotcha. That always comes up with brain metastasis is prognosis. I know it’s going to be different for individual patients, but how do you address that?
[00:49:59] Dr Ahmed: Yeah. So I think that’s an important question. I think that’s really a discussion that needs to take place on an individual basis with the patient, with their provider, to judge not only the treatment that has taken place of the brain metastasis, but then also their overall systemic treatment.
The burden of cancer throughout the whole body to, and potential options are still available for patients. We’ve made a lot of strides in the management of brain metastasis to improve outcomes, but I think we have a long way to go.
[00:50:30] Lianne Kraemer: Is there a standard timeframe after receiving radiation for recurrence or is it different for everyone or what’s the likelihood of recurrence after radiation?
[00:50:42] Dr Ahmed: We do a pretty good job with treating the areas that we can see when we treat with stereotactic radiation treatments, overall, the control rates and the areas that we treat are about 90% or so. However, because it’s adjust focused radiation treatment. Unfortunately the cancer can come back in areas that we don’t treat.
And that’s why we really continue to monitor with MRI. Quite regularly between two to three months, for the first year after receiving stereotactic radiation treatment to monitor for the growth of additional sites of cancer, it’s hard to predict in every patient what that interval would be, but that’s why we order those MRIs at pretty regular intervals across all patients, to make sure that if there are new brain metastasis that do occur, or even in the area that we have previously treated, that they’re caught early, so they can be managed appropriate.
[00:51:36] Lianne Kraemer: Okay. And what about management? You listed the side effects during the presentation. What kind of medication or how do you manage the side effects such as fatigue? Are there things that help have those side effects?
[00:51:51] Dr Ahmed: Yeah. So certainly sometimes from the delivery of the radiation treatment or from the metastasis themselves, or it can be a DEMA that surrounds metastasis.
So that is managed with steroids. That’s the, one of the primary tools that we use. And then I mentioned the mantem for um, some of the memory changes that can occur with whole brain radiation treatment. There’s anti-seizure medications that are prescribed as well as prophylaxis sometimes for potential seizure active.
[00:52:22] Lianne Kraemer: Okay. And we are just about out of time. Is there a recommendation, someone who’s just been diagnosed with brain mets?
[00:52:30] Dr. Aixa Soyano: This session with their provider and the clinician. We are a team. So we’re all trying to help take care of you, but it is a multidisciplinary team just having that trust and conversation.
Uh, No, what to expect. Ask if you don’t know if you’re afraid we’re here, we’re doing this every day. So we probably have most of the answers that come through our patients’ heads. It is a journey. So it’s just, we’re along for the ride. Okay,
[00:52:58] Lianne Kraemer: thank you to Dr. Soyano and Dr. Ahmed for a very informative program. This has been a great hour.
I did want to let everyone know that we’ve been hard at work, creating a website that is dedicated to breast cancer, brain metastasis, as well as leptomeningeal disease. It’s a resource for patients. You’ll be able to find it at MBC brainmets. Org. So once again, thank you to our speakers and audience. We are grateful for your presentation and attendance.
[00:53:32] Dr Ahmed: Thank you.
[00:53:34] Lisa Laudico: This podcast is produced and edited by me. Lisa Laudico sound design and original music from Konner Kienzle and Samantha Silverstein. Our executive producer is Christine Benjamin, senior director of. patient services and education and share cancer support. You can find more episodes of our MBC life, wherever you get your podcasts.
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