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Metastatic Breast Cancer Treatment Decisions: Which Path is Best for You?

Metastatic Breast Cancer Treatment Decisions: Which Path is Best for You? from Patient Empowerment Network on Vimeo.

 For each metastatic breast cancer patient, there are several variables to consider to access the best treatment path. Dr. Lisa Flaum explains key factors to consider, and discusses how the risks and benefits are weighed when making treatment decisions for an individual patient.

Dr. Lisa Flaum is a Medical Oncologist at the Robert H. Lurie Comprehensive Cancer Center of Northwestern University. Learn more here.

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Transcript:

Dr. Flaum:                  

So, when we’re determining a treatment approach, there are a number of variables. So, to some degree, based on a patient’s individual characteristics, their age, their other health issues, may guide what treatments are available or indicated or even desirable from a patient’s standpoint. To some degree, the locations and extent of disease are important. So, if someone has cancer and that’s causing a particular symptom, with bony sites being a particular example, there may be a role for something targeted; Something like radiation, and in rare cases, surgery to target a specific symptomatic or worrisome spot of metastatic cancer.

In general, the mainstay of treatment for metastatic breast cancer is what we call systemic treatment or medical treatment, treatment that’s going to go everywhere and treat the cancer wherever it is. In some situations, we may be deciding between more or less aggressive treatment, and the locations and sites of disease may be important in determining that. If someone has extensive disease, for instance in a vital organ like the lung, the liver, the brain, we may start with something more versus less aggressive to try to get it better under control quickly. Whereas people with more limited metastatic disease may be able to start with something less aggressive.

And then beyond that, a lot of the decision-making is based on those molecular markers that I alluded to, which are defined by the hormone receptor status. So, whether the tumor expresses those estrogen and progesterone receptors, and whether the tumor over-expresses HER2. And then to a lesser degree, based on other markers that may be defined by additional tests.

So, every treatment discussion we have is a two-way street. So, our job is to present the data, present options, present recommendations. And often, we have an opinion on where we would fall and if there are a number of different options. But to me, it’s a collaborative discussion. And if there are options, it’s weighing what potential benefit do we get from a single option or from adding something to that particular option versus what are the downsides? And some of it is discussion about logistics. Do we do something IV versus oral? Is there a particular side effect that we’re hoping to avoid, such as hair loss? Which of course, we’re trying to avoid. Some treatments may have a higher likelihood of working, but a higher likelihood of causing hair loss. That may factor into our decision.

So, whether it’s the first decision point when we’re deciding on preliminary therapy or future decision points as we go through this journey, there is always a discussion about this is where we are, these are what our options are. Here’s how we’re going to weigh the pros and cons. And then it comes back to a collaborative decision about how we weigh the risks and rewards and where we’re going with an individual patient.

So, clinical trials are always part of at least the conversation, so they’re always a consideration at each step of our discussion. So, from a preliminary treatment standpoint, we’re always going to go through here are our standard options. Here’s, again, what we think is most appropriate. And if there’s a clinical trial that’s appropriate in that scenario, we’ll lay that out there as an option. So, a clinical trial is always worth discussing. It’s always worth asking that your doctor, “Is a clinical trial appropriate for me at this point?” But it’s not always the right recommendation.

So, there are a lot of scenarios, especially at the beginning of treatment for metastatic disease where we have so many options, and so many new and novel treatment options and drugs that have been approved fairly recently that have defined the standard of care, that the standard is going to be often what we recommend. And a clinical trial may be something that we would use if that treatment fails to work or at some future point down the line. And at other points in time, we have very good, appropriate clinical trials that could be indicated at any step along the way. So, it’s worth the discussion. Whether it’s the recommendation or not depends on the circumstances, it depends on the time. What we have today was very different than what we might’ve had available six months ago and six months from now. But clinical trials are out there, and if the location that a patient is going doesn’t have access to clinical trials, it’s always reasonable to ask too, “Should I be going somewhere else to see if a clinical trial is appropriate?”

Essential Testing Following A Metastatic Breast Cancer Diagnosis

Essential Testing Following a Metastatic Breast Cancer Diagnosis from Patient Empowerment Network on Vimeo.

Following a metastatic breast cancer diagnosis, what tests are essential? Dr. Lisa Flaum reviews the role of key tests, and the impact of molecular (genetic) test results on treatment decisions.

Dr. Lisa Flaum is a Medical Oncologist at the Robert H. Lurie Comprehensive Cancer Center of Northwestern University. Learn more here.

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Transcript:

Dr. Flaum:                  

When someone has either a diagnosis or a suspected diagnosis of metastatic cancer, meaning a diagnosis of cancer that has spread somewhere outside of the breast. And the most important initial step is establishing a tissue diagnosis. So, we could have our suspicions based on imaging, based on symptoms, but the most important thing is to confirm it. And usually that confirmation involves some type of tissue biopsy. So, collecting cells, examining them under the microscope, making sure that the diagnosis in fact, is cancer. Making sure that the cancer has spread from the breast, which is something that is definable under the microscope for the most part. And then evaluating various molecular markers within the tumor itself that are critical to guiding treatment.

So, in addition to the tissue diagnosis, the other important first step is what we call cancer staging. So, establishing the extent of the tumor within the body, which typically involves some type of scans, which may be variable depending on the situation or depending on the physician often could be a CT scan and a bone scan, maybe a PET scan. There may be an MRI.

So, a number of different tests that help us establish where the tumor is at baseline, so we can better understand the anatomy, but also to follow down the road to establish whether any given treatment is working. There are also maybe discussions of other types of molecular testing beyond what we determined in terms of the traditional biologic markers. You might hear the terms next generation sequencing tests like Foundation, Guardant, Tempus, which better define the cancer’s biology, which increasingly is becoming useful in terms of targeting treatment to someone’s specific cancer.

So, the molecular tests are looking at a few different things. So, first and foremost from a breast cancer standpoint, the most important basic molecular markers are what we consider to be the four main receptors, which is the estrogen and progesterone receptor, which dictates whether a given tumor is driven by estrogen and importantly dictates whether anti-estrogen therapy is going to be an appropriate component of the treatment. The other basic marker is called HER2, which is a protein that’s over-expressed.

In about 20% of breast cancer patient cells, and it’s also very critical in terms of guiding treatment. For specific types of breast cancer, once we know those preliminary molecular markers, then there’s an array of other types of anomalies within the tumor itself that could help to guide specific treatment. So, a couple of examples, and I can talk about that when you talk about treatment. If someone has a genetic predisposition to breast cancer with a BRCA mutation, there’s a specific treatment that might be appropriate. More recently, there’s another abnormality that can be detected by these tests called a PI3-Kinase mutation that identifies a population of patients who could be appropriate for another type of targeted therapy. So, for an individual, knowing what their particular profile is, whether or not those treatments are going to be indicated right at the beginning of treatment or maybe something that we use down the road. Inevitably, they’re going to help us understand what our tools are when we’re helping to make those decisions.

What Could Advances in Breast Cancer Research Mean for You?

What Could Advances in Metastatic Breast Cancer Research Mean for You? from Patient Empowerment Network on Vimeo.

What should metastatic breast cancer patients know about emerging approaches to treatment and care? Dr. Julie Gralow reviews developments in metastatic breast cancer research, including advances in genetics, subsetting disease and personalized medicine.

Dr. Julie Gralow is the Jill Bennett Endowed Professor of Breast Medical Oncology at the University of Washington, Fred Hutchinson Cancer Research Center, and the Seattle Cancer Care Alliance. More about this expert here.

See More From INSIST! Metastatic Breast Cancer

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What Could Metastatic Breast Cancer Genetic Testing Advances Mean for You?

What Are Essential Genetic Tests for Metastatic Breast Cancer Patients?

Metastatic Breast Cancer: Debunking Common Misconceptions

 

Transcript:

Katherine:                  

There have been so many advances in breast cancer research. What are you excited about in research right now?

Dr. Gralow:                

Well, every single drug that’s been approved, every single new regimen that’s been approved in breast cancer is the direct result of clinical trials, and this is a major part of my career, is to help patients get access to clinical trials and run important clinical trials that could lead to new discoveries – is this regimen better? What’s the toxicity?

Because until we have a cure for breast cancer, we need to do better, and we need to research better treatment options. So, doing trials, having access to clinical trials where you can participate, help move the science forward is key.

I think where we’re moving with breast cancer is the more we’re understanding the patient and the tumor, the more we’re realizing every single breast cancer is different, actually, and whereas when I started my training 20-plus years ago, breast cancer was breast cancer – we weren’t even using HER2 yet, we were just learning how to use estrogen receptor, and we kind of treated everything the same – now, we’re subsetting, and subsetting, and subsetting. Even in triple negative breast cancer now, which is about 18-20% of breast cancer, we’re subsetting.

Does that triple negative breast cancer have PD-L1, which is associated with being able to get immunotherapy drugs? Does it express androgen receptor? Because sometimes, even a breast cancer that doesn’t have estrogen or progesterone receptor can express the androgen receptor, like prostate cancer, and we can use some prostate cancer drugs. So, even triple negative breast cancer we’re subsetting and subsetting, and could that triple negative breast cancer be associated with a BRCA1 or 2 mutation, and then we can use the PARP inhibitors?

So, I’m actually really excited about that we’re learning more and more, and subsetting, and not treating breast cancer as one size fits all, and if we can better tailor the treatments to the patient and the tumor, that we are going to get to the point where I can tell my patients yes, we can get cures in metastatic breast cancer.

What is the Role of Genetic Testing in Breast Cancer?

What is the Role of Genetic Testing in Breast Cancer? from Patient Empowerment Network on Vimeo.

Breast cancer expert Dr. Julie Gralow discusses the role of genetic testing in metastatic breast cancer care, reviewing the impact of inherited–and acquired–genetic mutations on treatment options.

Dr. Julie Gralow is the Jill Bennett Endowed Professor of Breast Medical Oncology at the University of Washington, Fred Hutchinson Cancer Research Center, and the Seattle Cancer Care Alliance. More about this expert here.

See More From INSIST! Metastatic Breast Cancer

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What Could Metastatic Breast Cancer Genetic Testing Advances Mean for You?

What Are Essential Genetic Tests for Metastatic Breast Cancer Patients?

Metastatic Breast Cancer: Debunking Common Misconceptions

 

Transcript:

Katherine:                  

All right. Dr. Gralow, when you meet with patients, what are some of the more common misconceptions that you hear related to diagnosis?

Dr. Gralow:                

Well, I think people do confuse – especially at an early diagnosis – that the metastases, the travel to the local lymph nodes, is not the same as a metastatic breast cancer, so we spend some time talking about how it’s still curable and not considered a distant metastasis if the lymph nodes are in the armpit or up above the collarbone, and so, that’s something that we spend some time talking about.

This whole term of “metastatic recurrence” – unfortunately, when you start looking online and get your information from Dr. Google, you read right away that it’s no longer curable, and in 2020, yes, that’s true. That’s probably the most specific statement that we can make. We are not going with curative intent, which means we treat for a defined amount of time, and then all the disease goes away, and we stop treatment, and then you go on with your life, and it never comes back. That would be cure.

But, I think it’s really important to point out that much of metastatic breast cancer can be highly treatable, and what we hope to do – and certainly, at least a subset of metastatic breast cancer – we want to convert it more to what we would call a chronic disease, and so, think of it more like hypertension, high blood pressure, or diabetes. These are diseases that we generally don’t cure with treatment, but that we can control with drug therapy, which sometimes has to be adjusted, and if we don’t control it, we can get some bad complications.

So, that’s not all metastatic breast cancer, unfortunately – we can’t convert all of it to something where we can use a therapy for a long time that keeps it in check and where you have a pretty good quality of life – but we’re hoping that more and more, we’re getting targeted therapies and more specific treatments to patients so that we can convert more patients to a more chronic kind of situation.

Katherine:                  

Many people are confused about genetic testing. They often think that it relates to ancestry or physical traits like hair and eye color. What’s the role of genetic testing in breast cancer?

Dr. Gralow:                

Well, you can do genetic testing of the patient’s inheritance, which is how most people think of genetic testing, and that’s actually really important and increasingly important in metastatic breast cancer to do your own inheritance. Have you inherited a gene that was associated with how your cancer developed? Because now, we actually have a class of drugs called PARP inhibitors that are approved for tumors that have a BRCA1 or BRCA2 mutation with them. Most of those mutations were inherited, but not all. Sometimes they can develop as well.

So, now, when my patient – if she didn’t previously have genetic testing for an inherited risk for breast cancer either coming from mom or dad’s side of the family, a lot of people do have that up front, especially if they’re younger at diagnosis or they have a lot of family members with breast cancer. If she didn’t have that genetic testing done previously, at the time of the metastatic occurrence, I’m going to recommend that that be done because knowing if the cancer is associated with one of these DNA repair genes – BRCA1, BRCA2, some other genes – we have a new treatment option, which is an oral pill that actually is highly effective if the tumor has a mutation in one of these.

But, we can also – so, that’s genetic testing of the patient’s own DNA, but we can also do what we call genetic testing – or genomic testing, if you will – of the genes of the cancer. What were the changes in the DNA at the gene level that caused a normal breast cell over time to develop into a cancer cell that’s now growing without responding to our body’s checks and balances? So, what were those mutations, deletions, or amplifications in the tumor itself?

So, we’ve got the patient’s genetics, we’ve got the tumor’s genetics, and both of those come into play when we’re making our best treatment recommendations and trying to understand what the right approach is.

Katherine:                  

How is testing administered?

Dr. Gralow:                

So, for our inherited testing, those gene changes can be found in every cell in the body, so we can do that from a simple blood test where we just look at the blood cells. We can actually do it with our sputum and with a cheek swab, even. You can get enough of the DNA from the inside of the mouth to do that.

For a tumor’s genetics, we need some of the tumor, so that’s either done with a biopsy into the metastatic site or, as I mentioned before, increasingly, we’re exploring the potential for a liquid biopsy – so, drawing some blood and then trying to find pieces of the tumor that are shed into the blood.

Factors That Guide a Metastatic Breast Cancer Treatment Decision

Factors that Guide a Metastatic Breast Cancer Treatment Decision from Patient Empowerment Network on Vimeo

Dr. Julie Gralow discusses factors that affect metastatic breast cancer treatment decisions, including the cancer’s biology, the overall health of the patient, and treatment side effects.

Dr. Julie Gralow is the Jill Bennett Endowed Professor of Breast Medical Oncology at the University of Washington, Fred Hutchinson Cancer Research Center, and the Seattle Cancer Care Alliance. More about this expert here.

See More From INSIST! Metastatic Breast Cancer

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What Could Metastatic Breast Cancer Genetic Testing Advances Mean for You?

What Are Essential Genetic Tests for Metastatic Breast Cancer Patients?

Metastatic Breast Cancer: Debunking Common Misconceptions

 

Transcript:

Katherine:                  

Well, Dr. Gralow, what other factors should be taken into consideration with a treatment route?

Dr. Gralow:                

I always like to think of the treatment decision as relying on three factors, and the first relates to the tumor factor, the cancer factor.

So, we talked a lot about the biology, the estrogen receptor, the HER2, the genomic profiling. So, that’s critical, but there are two other components that we need to really strongly consider when trying to devise the right treatment regimen. One of those is patient factors, and not just the patient’s genetics, but are they pre- or post-menopausal?

What is the age? Where are they in life? Are they young with young kids? Are they working, and is that an important priority for them? Are they older and with grandchildren, and they don’t need to work? What is it that would be critical? What are the patient’s priorities here, and what are their fears, what are the things they would – what would be really important as we plan a regimen? And so, the patient factors which would be patient priorities and where they are in life right now.

And then, there’s factors related to the treatment itself, which would include not just how effective it is, but – and, this is really important when trying to decide regimens – what are the side effects of a regimen? For some patients, hair loss is a big deal, and we can put it off as long as possible – maybe choosing the first couple regimens don’t cause hair loss sometimes.

But, for other people, that doesn’t matter to them. For some, we have oral – some regimens, and that could keep them out of the infusion room, and others actually – I’ve had patients who actually like coming into the infusion room regularly so that they can review the side effects and get the reassurance provided by it. So, we’ve got different route of administration of the drugs, different side effects. If you already had, for example, a neuropathy – a numbness/tingling of fingers and toes – from treatment that you might have gotten for early-stage disease, we’d probably want to avoid drugs where that’s their major side effect in the metastatic setting and that would increase that even further.

We’ve got some drugs that cause a lot of toxicity to our GI system – nausea, vomiting, or diarrhea – and other drugs that don’t. And so, understanding what symptoms the patient already has and actually tailoring the treatment based on some of the side effects of the drug could also be done, as well as how they’re administered. So, again, patient factors, tumor factors, and then, factors related to the treatment itself all come into play when we make decisions.

Katherine:                  

There have been so many advances in breast cancer research. What are you excited about in research right now?

Dr. Gralow:                

Well, every single drug that’s been approved, every single new regimen that’s been approved in breast cancer is the direct result of clinical trials, and this is a major part of my career, is to help patients get access to clinical trials and run important clinical trials that could lead to new discoveries – is this regimen better? What’s the toxicity?

Because until we have a cure for breast cancer, we need to do better, and we need to research better treatment options. So, doing trials, having access to clinical trials where you can participate, help move the science forward is key.

I think where we’re moving with breast cancer is the more we’re understanding the patient and the tumor, the more we’re realizing every single breast cancer is different, actually, and whereas when I started my training 20-plus years ago, breast cancer was breast cancer – we weren’t even using HER2 yet, we were just learning how to use estrogen receptor, and we kind of treated everything the same – now, we’re subsetting, and subsetting, and subsetting. Even in triple negative breast cancer now, which is about 18-20% of breast cancer, we’re subsetting.

Does that triple negative breast cancer have PD-L1, which is associated with being able to get immunotherapy drugs? Does it express androgen receptor? Because sometimes, even a breast cancer that doesn’t have estrogen or progesterone receptor can express the androgen receptor, like prostate cancer, and we can use some prostate cancer drugs. So, even triple negative breast cancer we’re subsetting and subsetting, and could that triple negative breast cancer be associated with a BRCA1 or 2 mutation, and then we can use the PARP inhibitors?

So, I’m actually really excited about that we’re learning more and more, and subsetting, and not treating breast cancer as one size fits all, and if we can better tailor the treatments to the patient and the tumor, that we are going to get to the point where I can tell my patients yes, we can get cures in metastatic breast cancer.

How Genetic Mutations Affect Metastatic Breast Cancer Prognosis and Treatment

How Genetic Mutations Affect Metastatic Breast Cancer Disease Progression and Prognosis from Patient Empowerment Network on Vimeo.

Dr. Julie Gralow explains the impact of genetic mutations on metastatic breast cancer progression and prognosis, including how DNA repair genes function. 

Dr. Julie Gralow is the Jill Bennett Endowed Professor of Breast Medical Oncology at the University of Washington, Fred Hutchinson Cancer Research Center, and the Seattle Cancer Care Alliance. More about this expert here.

See More From INSIST! Metastatic Breast Cancer

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Metastatic Breast Cancer Staging: What Patients Should Know

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Metastatic Breast Cancer: Debunking Common Misconceptions

 

Transcript:

Katherine:                  

You’ve been referring to a number of terms. Patients may have heard the BRCA or “braca” that relate to breast cancer in genetics. Would you give us an overview of common mutations in breast cancer?

Dr. Gralow:

So, of the mutations that we can inherit, the first two that were discovered were BRCA1 and BRCA2, and for all breast cancer – not just metastatic, but all breast cancer – we think that maybe 5-10% of breast cancer is the direct result of the inheritance of a strong gene that gives you a high – not 100%, but a high likelihood of developing breast cancer.

So, for BRCA1 and 2, these two genes are associated predominantly with breast and ovarian cancer, and if you live out your normal lifespan, you could have up to a 75-80% chance of getting one of those two cancers, and breast cancer being more common. Also, some association with some other cancers including, interestingly, prostate cancer, which we’re learning more about.

So, BRCA1 and 2 are the most common, and they tend to be found – because they have such a high association with the risk of breast and ovarian cancer, they tend to be found in families that have a lot of other breast cancers, and also breast and ovarian cancer presenting at a younger age. So, you’ve inherited a gene that leads to a high predisposition, and the cancer occurs earlier.

So, whereas the average age of diagnosis of breast cancer in the U.S. is 61-62 most commonly, in a patient who’s inherited a BRCA1 or 2 gene mutation, it’s closer to 40-42 – so, a lot younger. And then, there are a variety of other genes that can be inherited that are either much less common or have a weaker link. So, for example, there are genes called CHEK2 or PALB2, ATM, P53 – I just mention that because some of the listeners will potentially have one of those mutations or have heard it. Those are either rarer or they’re associated with a weaker chance of getting cancer.

So, those might be more commonly found in a family that doesn’t have a lot of cancer in it because a carrier – the mother or the father – and their other relatives would have maybe only a 30% chance of getting breast cancer in some cases. So, there would be a lot of carriers who don’t get cancer.

So, as I mentioned earlier, I think it’s really important – especially right now in metastatic breast cancer – that pretty much everybody, even if you didn’t have a strong family history, even if you weren’t diagnosed at a young age, get tested because if we find one of these inherited mutations, we now have some additional treatment options, especially right now, approved for BRCA1 or 2, but clinical trials going on for many of these other genes.

Katherine:                  

How do these mutations affect disease progression and prognosis?

Dr. Gralow:                

So, most of the genes I’ve mentioned – in their normal state, they’re critical, actually. They’re called DNA repair genes, and their job in our life is when we accidentally make a mistake when we’re replicating our DNA and two cells are dividing, if there’s a mistake in the DNA, they go in and repair it. And, we’ve got all kinds of mechanisms to try to prevent mutations from happening as cells divide, and BRCA1 and 2 are a key part of that, and so, they’re fixing it.

So, if you inherit a mutation in one of those genes, you still have some ability to repair any routine mistakes that are being made, but over time, you have less ability, and then, if you get a cancer that has a deficiency in BRCA1 or 2, those cancers can be more sensitive to certain kinds of chemotherapy that affects DNA repair.

So, for example a class of chemotherapy agents called the platinum drugs – carboplatin and cisplatin – may be more effective in BRCA1- or 2-mutated cancers, also more generally in triple negative breast cancer because they can be more similar to BRCA1-mutated cancers in a lot of ways.

So, to go back to your original question, once a cancer has developed in a patient who has a BRCA1 or 2 mutation, we treat that cancer for what it is. So, it might have developed estrogen – have estrogen receptor on the surface or HER2, so we treat it as the subtype that developed, and actually, the chance of cure is just the same for BRCA1-associated breast cancer as it would be for one that doesn’t have a BRCA.

But, the chance of getting a second breast cancer – a totally new breast cancer – would be higher unless you chose to remove both of your breasts and the bulk of your breast tissue. So, decisions like surgery – if you had a known BRCA1 mutation, we’d treat the cancer you have now aggressively and for cure, but when you talk about your surgery options, we’d say doing more aggressive surgery, like removing both of your breasts – that’s not going to improve your chance of surviving the cancer you have now, but it will markedly reduce the chance of getting a second breast cancer.

So, you could consider that as an option for surgery – not to improve your chance of this cancer, but to reduce the chance of another breast cancer. So, your surgery decisions might be impacted by knowing your BRCA1 or 2 mutation. And then, clearly, if you had metastatic breast cancer, knowing if you had the option of a PARP inhibitor, one of the drugs in that class could be – you could have a different treatment option for drug therapy.

What Could Metastatic Breast Cancer Genetic Testing Advances Mean for You?

What Could Metastatic Breast Cancer Genetic Testing Advances Mean for You? from Patient Empowerment Network on Vimeo.

How do genetic testing advances impact metastatic breast cancer patients? Dr. Julie Gralow discusses these advances, including treatment developments, and the importance of retesting over time. 

Dr. Julie Gralow is the Jill Bennett Endowed Professor of Breast Medical Oncology at the University of Washington, Fred Hutchinson Cancer Research Center, and the Seattle Cancer Care Alliance. More about this expert here.

See More From INSIST! Metastatic Breast Cancer

Related Resources:

 

How Genetic Mutations Affect Metastatic Breast Cancer Disease Progression and Prognosis

Factors That Guide a Metastatic Breast Cancer Treatment Decision

How Can You Advocate for the Best Breast Cancer Care?

 

Transcript:

Katherine:                  

What advances have there been in testing?

Dr. Gralow:                

Well, it used to be – just going back a couple of years ago – that we didn’t do a lot of this genetic testing or genomic profiling of the tumor because we didn’t have many – the term is an “actionable mutation.” So, if we found something, would we do something with it? Did we have a drug we could use to do it? But, more and more and more, even in breast cancer, we’re finding actionable mutations that would drive therapy.

For example, in estrogen receptor positive breast cancer, we have a new class of targeted therapies called PI 3-kinase inhibitors – a drug called alpelisib or Piqray was approved in the last couple of years in that category – and it only is effective in estrogen receptor positive breast cancer that has a mutation in the PI 3-kinase gene. So, that would be something we’re looking for in the tumor’s genes, and actually, we need to know that there’s a mutation to even get the drug approved for treatment because it doesn’t work if you don’t have that mutation.

Increasingly, we’re finding some changes that can happen in the estrogen receptor gene and the HER2 gene, interestingly, so that you can have estrogen receptor expressed on your tumor, but over time, that tumor might develop an estrogen receptor mutation so that it stops responding to certain drugs that target the estrogen receptor.

And so, that’s called an ESR1. That’s the name of the estrogen receptor gene – an ESR1 mutation – and that would tell me probably not going to respond as well to a drug in the class we call aromatase inhibitors, but might respond better to a drug in the class that we call the selective estrogen receptor degraders like fulvestrant or Faslodex, is the name of a drug in that class.

We’re also finding that you can have what we call activating mutations in HER2, and they can be present whether the tumor overexpresses HER2 or not, and we’ve got some ongoing clinical trials looking at if the tumor doesn’t have extra HER2 on its surface – so, it doesn’t have extra HER2 protein, but at the gene level, it’s got an activated HER2 gene – we can use certain types of HER2 therapy to treat it, and we’re testing that right now in clinical trials.

So, could we even use some HER2 drugs even though technically, the tumor would be classified as HER2 negative? So, fascinating increasing information that we’re understanding, and I also mentioned before we can inherit mutations in genes such as BRCA1 and 2, but fascinatingly, the tumor can acquire those mutations. Even if we didn’t inherit a mutation, we can see mutations in the BRCA1 and 2 gene – we call those somatic as opposed to germline mutations. So, “germline” means it’s in every cell in your body, but “somatic” means the tumor somehow acquired this over time.

And so, we’ve done – we just presented some very early results of a trial, and we’re expanding this trial, looking at if you didn’t inherit a BRCA1 or 2 mutation, so technically, you don’t qualify for a PARP inhibitor, but if the tumor acquired a mutation and we can prove that with testing the tumor’s DNA, then we have seen responses from these PARP inhibitors, so that opens up another whole class of treatments, and there are other DNA repair genes that actually may be qualified as well that we can inherit or that can be acquired by the tumor.

So, more and more, we’re doing this genomic profiling, and it is leading to results that would give us possible treatment options.

Katherine:                  

Dr. Gralow, the goal of this program is to provide the confidence and tool for patients to advocate for the essential tests to get best care personalized to them. Are there specific tests that patients should make sure they have?

Dr. Gralow:                

Well, there are a lot of assays out there to do this genomic profiling or genetic testing of the tumor, so I don’t promote any one. Various institutions do it and do it well, various companies do it, but I think every metastatic patient should have the tumor looked at in this kind of profiling.

I also think every metastatic patient should advocate for having a biopsy of their cancer, and if a biopsy cannot be done safely in the recurrence, then see if they could get a liquid biopsy – have blood drawn to find it. So, I think that patients should be asking about this. Sometimes, insurance won’t always cover it, and so, my job as a treating physician is to advocate for that, to do an appeal.

More and more, because we have so many actionable mutations in breast cancer now, I’m not having insurance decline, but occasionally, it does, and then it’s our job as the healthcare providers to make the case that yes, this will impact the patient, and yes, it should be covered by insurance.

Metastatic Breast Cancer: Debunking Common Misconceptions

Metastatic Breast Cancer: Debunking Common Misconceptions from Patient Empowerment Network on Vimeo.

Dr. Julie Gralow debunks common misconceptions about metastatic breast cancer, including the metastatic diagnosis itself and why genetic tests are important. 

Dr. Julie Gralow is the Jill Bennett Endowed Professor of Breast Medical Oncology at the University of Washington, Fred Hutchinson Cancer Research Center, and the Seattle Cancer Care Alliance. More about this expert here.

See More From INSIST! Metastatic Breast Cancer

Related Resources:

How Genetic Mutations Affect Metastatic Breast Cancer Disease Progression and Prognosis

Factors That Guide a Metastatic Breast Cancer Treatment Decision

What Could Metastatic Breast Cancer Genetic Testing Advances Mean for You?

 


Transcript:

Katherine:                  

All right. Dr. Gralow, when you meet with patients, what are some of the more common misconceptions that you hear related to diagnosis?

Dr. Gralow:                

Well, I think people do confuse – especially at an early diagnosis – that the metastases, the travel to the local lymph nodes, is not the same as a metastatic breast cancer, so we spend some time talking about how it’s still curable and not considered a distant metastasis if the lymph nodes are in the armpit or up above the collarbone, and so, that’s something that we spend some time talking about.

This whole term of “metastatic recurrence” – unfortunately, when you start looking online and get your information from Dr. Google, you read right away that it’s no longer curable, and in 2020, yes, that’s true. That’s probably the most specific statement that we can make. We are not going with curative intent, which means we treat for a defined amount of time, and then all the disease goes away, and we stop treatment, and then you go on with your life, and it never comes back. That would be cure.

But, I think it’s really important to point out that much of metastatic breast cancer can be highly treatable, and what we hope to do – and certainly, at least a subset of metastatic breast cancer – we want to convert it more to what we would call a chronic disease, and so, think of it more like hypertension, high blood pressure, or diabetes. These are diseases that we generally don’t cure with treatment, but that we can control with drug therapy, which sometimes has to be adjusted, and if we don’t control it, we can get some bad complications.

So, that’s not all metastatic breast cancer, unfortunately – we can’t convert all of it to something where we can use a therapy for a long time that keeps it in check and where you have a pretty good quality of life – but we’re hoping that more and more, we’re getting targeted therapies and more specific treatments to patients so that we can convert more patients to a more chronic kind of situation.

What Are Essential Genetic Tests for Metastatic Breast Cancer Patients?

What Are Essential Genetic Tests for Metastatic Breast Cancer Patients? from Patient Empowerment Network on Vimeo

Genetic tests can help guide metastatic breast cancer care. Dr. Julie Gralow discusses essential genetic tests for metastatic breast cancer, and how results impact treatment decisions.

Dr. Julie Gralow is the Jill Bennett Endowed Professor of Breast Medical Oncology at the University of Washington, Fred Hutchinson Cancer Research Center, and the Seattle Cancer Care Alliance. More about this expert here.

See More From INSIST! Metastatic Breast Cancer

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How Genetic Mutations Affect Metastatic Breast Cancer Disease Progression and Prognosis

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What Could Metastatic Breast Cancer Genetic Testing Advances Mean for You?

 


Transcript:

Katherine:                  

For a patient to get diagnosed, what are the essential tests?

Dr. Gralow:                

So, we’re talking about metastatic breast cancer here, and in the U.S., maybe up to 10% or slightly less of breast cancer is technically Stage 4 or metastatic at diagnosis. That means at the time we first found it in the breast, it had already spread beyond. So, an important thing that we’ll do with a newly diagnosed breast cancer is especially if there are a lot of lymph nodes are involved or the patient has symptoms that might say there’s something in the bone, liver, or lung is staging.

So, we’ll use scans – maybe a CAT scan, bone scan, or PET scan – and we will look at whether the disease has gone beyond the breast and the lymph nodes, and if so, where. So, maybe 8-10% of breast cancer diagnosed in the U.S. already has some evidence that it has spread beyond the breast, but the most common way that metastatic breast cancer happens is that a patient was diagnosed possibly years and years ago, treated in the early-stage setting, and now it comes back, and that is the most common presentation for metastatic breast cancer, and sometimes that can be due to symptoms.

As I said, if it comes back in the bone, maybe that’s bone pain. If it’s in the lung, it’s a cough. There are symptoms. Sometimes, it’s because we’ve done a blood test or something and we find some changes there.

And so, when a breast cancer has recurred, it’s really important to document that it’s really breast cancer coming back, first of all, and so, if we can, we generally want a biopsy, and we want to stick a needle in it if it’s safe to do, and look and verify that it looks like breast cancer, and also, it’s really important that we repeat all those receptors that we talked about from the beginning because it can change.

So, a cancer up front 10 years ago could have been positive for estrogen receptor, but the only cells that survived – mutated, changed – were estrogen receptor negative, so what comes back could be different. So, it’s really critical to get that biopsy, repeat the estrogen/progesterone receptor and HER2, and also, in an ideal world, now that it’s 2020 and we’re moving more toward genomics, to do a full genomic profile and look for other changes and mutations that could drive our therapeutic options.

So, staging, knowing where the cancer is, getting a good baseline by understanding where it is and how big it is so that we can follow it and hopefully see that it’s responding to treatment, and then, repeating all of the biology components so that we know what the best options are for treatment are really critical.

Katherine:                  

Right. How can patients advocate for a precise breast cancer diagnosis, and why is that important?

Dr. Gralow:                

Well, all those things I just mentioned are key. Knowing exactly where it is so that we can monitor it – for example, if the cancer has come back in the bones, we would add what we call a bone modifying agent, a drug like zoledronic acid or denosumab – Zometa or Xgeva – which can suppress bone destruction from the cancer, but if it’s not in the bone, we wouldn’t add that.                                   

And, we want to have a good look everywhere so that we can see if it’s responding because sometimes, the tumor can respond differently in one area than another. Also, I think it’s really important to know what your treatment options are by doing that biopsy, getting a full panel, and looking at potentially hundreds of genes that could be mutated, deleted, or amplified so that we know what our treatment options are.

And, we’re not going to use all the treatment options up front, so it’s helpful for knowing that if this treatment doesn’t work or is too toxic, what are the second-line or third-line options? So, we make sure that there’s what we call good staging up front so we know where the cancer is, and then we make sure that we’ve looked at it as best we can in 2020 with all the genomics.

 That would give us the best chance of being tailored – individualized – to the tumor. Sometimes, if we can’t biopsy it, like with a needle that would go into a liver spot, then increasingly, we’re looking at what we call liquid biopsies, and that can be drawing the blood and seeing if we can find parts of the tumor, whether it be the DNA or the RNA that’s floating around in the blood, and sometimes we can get that information out of the blood as well.

Metastatic Breast Cancer Staging: What Patients Should Know

Metastatic Breast Cancer Staging: What Patients Should Know from Patient Empowerment Network on Vimeo.

Breast cancer expert Dr. Julie Gralow discusses metastatic breast cancer staging, including prognostic staging, breast cancer subtypes, and the meaning of metastasis.

Dr. Julie Gralow is the Jill Bennett Endowed Professor of Breast Medical Oncology at the University of Washington, Fred Hutchinson Cancer Research Center, and the Seattle Cancer Care Alliance. More about this expert here.

See More From INSIST! Metastatic Breast Cancer

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What Are Essential Genetic Tests for Metastatic Breast Cancer Patients?

Metastatic Breast Cancer: Debunking Common Misconceptions

What Could Metastatic Breast Cancer Genetic Testing Advances Mean for You?

 


Transcript:

Dr. Gralow:                

The staging of breast cancer has traditionally been by something we call anatomic staging, which has the tumor size, the number of local lymph nodes involved, and whether it has metastasized beyond the lymph nodes. So, that’s TNM – tumor, nodes, metastases. And so, that’s the classic staging, and based on combinations of those things, you can be a Stage 0 through Stage 4. Stage 0 is reserved for ductal carcinoma in situ, which is a noninvasive breast cancer that can’t generally spread beyond the breast, so that’s Stage 0, and then we go up for invasive cancer.

Interestingly, just a couple years ago, the big group that oversees the staging of cancers decided that in breast cancer, that TNM – the size, the lymph nodes, and the location beyond the lymph nodes – is not good enough anymore, so they came up with a proposal for what we call a clinical prognostic stage, which is a companion to the traditional TNM staging.

What they were getting at here was it’s not just how big your cancer is, how many lymph nodes, or whatever, it’s also at the biology of your cancer. So, this new clinical prognostic stage takes into account the estrogen and progesterone receptor of your cancer, the HER2 receptor at the grade, which is a degree of aggressiveness, and then, if your tumor qualifies, one of the newer genomic testing profiles that we use in earlier-stage breast cancer, such as the Oncotype DX 21-gene recurrence score or the MammaPrint 70-gene assay.

So, all of that goes into account now, and the whole point here is that the estrogen receptor, the HER2, the grade, and some of these genomics may actually make more difference than how many lymph nodes you have, where the cancer is, and how big it is, so it’s not just the size, but also the biology of the cancer that we’re trying to include in the new staging systems.

Katherine:                  

In this program, Dr. Gralow, we’re focusing on metastatic breast cancer. Would you explain when breast cancer is considered to have metastasized?

Dr. Gralow:                

That’s a great question because technically, if the lymph nodes in the armpit – the axillary area – are involved, that does represent spread beyond the breast, but if it stays in the local lymph node areas, it’s not technically called a metastatic or Stage 4 breast cancer. So, metastatic breast cancer would have traveled beyond the breast and those local lymph nodes, and some common sites would be to the bone, to the lungs, to the liver, less commonly – at least, up front – to the brain, and it could also travel to other lymph node groups beyond those just in the armpit and the local chest wall area as well.

Katherine:                  

What about subtypes? How are they determined?

Dr. Gralow:                

The main way that we subtype breast cancer right now is based on the expression of estrogen and progesterone receptor, the two hormone receptors, and the HER2 receptor, the human epidermal growth factor receptor. So, to date, those are the most important features when we subtype, and so, a tumor can either express estrogen and progesterone receptor or not, and it can overexpress or amplify HER2 or not, and if you think that through, you can come up with four different major subtypes, in a way, based on estrogen receptor positive or negative and HER2 positive or negative.

When all three of those are negative, we call that triple negative breast cancer, and that’s about 18-20% of all breast cancers as diagnosed in the U.S. And then, when all three are positive, we sometimes call it triple positive, and the reason that we subtype is because we know that those different subsets act differently and that we have different drugs to treat them with, and we’ve got great drugs in the categories of hormone receptor positive and HER2 positive, and increasingly, some recently hope in a new drug approval or two in triple negative breast cancer as well.

Myeloma Targeted Therapy: Why Identifying Chromosomal Abnormalities is Key

Myeloma Targeted Therapy: Why Identifying Chromosomal Abnormalities is Key from Patient Empowerment Network on Vimeo.

Charise Gleason, a nurse practitioner, provides insight as to why identifying chromosomal abnormalities is essential when it comes to targeted therapy as a treatment choice for myeloma.

Charise Gleason is a nurse practitioner specializing in myeloma and serves as the Advanced Practice Provider Chief at Winship Cancer Institute of Emory University. Learn more about Charise, here.

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Essential Tests & Imaging After a Myeloma Diagnosis

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Transcript:

Charise:                       

So, testing for chromosome abnormalities or changes are important when it comes to targeted therapy.

And we used to think of this more in that relapse setting. But we also look at it upfront now, because it tells us more about the path of myeloma. And there are reasons to check throughout at relapse, again, to see if something’s changed. So, with targeted therapy, we can use the translocation (11;14), for instance.

Many patients have a translocation t(11;14). It’s not a high-risk feature. But we know on clinical trial we have a drug that we’re using called venetoclax that those patients can be very sensitive to.

And so, we’re looking at this not just in translocations but in sequencing for other abnormalities or gene mutations that can help guide us with these newer therapies. And you see that across all cancer types at this point. So, you can get very specific with a patient’s type of myeloma – that this drug is going to work better because you have this mutation.

So, we look at it upfront. It guides us for risk stratification: standard risk versus high risk. And then we look at it in that relapse setting. Do we have a drug or a clinical trial that this patient will respond better to because of those abnormalities?

When we’re risk stratifying, we know standard risk, medium risk, and high risk. Those are those translocations, those gene mutations, that we know about.

But newer testing, like sequencing, gives us a lot more mutations that we don’t even know what to do with them all yet.

We don’t necessarily have drugs for all of them, but it does help guide us down the road. So, right now some common are the translocations, but also deletion 17p, which we’ve known about for a while. But maybe you see a BRAF mutation, which you typically associate with other types of cancers, but we see that in myeloma as well.

So, it helps us look at is there a drug that our myeloma patient might benefit from because they have a BRAF mutation, for instance. 

Essential Imaging and Chromosome Tests after a Myeloma Diagnosis

Essential Imaging & Chromosome Tests After a Myeloma Diagnosis from Patient Empowerment Network on Vimeo.

Charise Gleason, a nurse practitioner, explains why tests such as bone marrow biopsy, FISH test and full-body imaging are considered essential for patients after a myeloma diagnosis.

Charise Gleason is a nurse practitioner specializing in myeloma and serves as the Advanced Practice Provider Chief at Winship Cancer Institute of Emory University. Learn more about Charise, here.

See More From INSIST! Myeloma

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Lab Tests in Myeloma: Key Results to Monitor

Key Considerations When Choosing Myeloma Treatment: What’s Available?


Transcript:

Charise:                       

The essential testing that a myeloma patient should undergo following a diagnosis is – obviously, you’ve had those diagnostic test labs, the 24-hour urine, some scans, but the specific things that we need are a bone marrow biopsy.

That includes cytogenetics and FISH, and we can talk a little bit more about that. You also want full-body imaging. We used to always use a skeletal survey, which was an X-ray of the long bones. But, really, the standard of care now is a whole-body scan.

So, depending on what your oncologist or your institution has, that would be a full-body CT scan, a PET-CT scan, or a full-body MRI. So, one of those tests is recommended. It’s not unusual if you have a PET. Like our institution, we use PET-CT. So, for a newly diagnosed patient, we’re also going to get an MRI of the spine for a further snapshot.

What we’re looking for with a full-body imaging is we want to make sure that there aren’t any lytic lesions.

So, with an X-ray, you have to have about 30 percent bone loss before it’s going to show up on an X-ray. So, those traditional X-rays that we used to use could actually miss an active lesion. So, in that diagnosis, we want to know that there is no active myeloma. And those other scans are going to be more specific to that.

So, the cytogenetics of a bone marrow biopsy are going to tell us more about the biology of the disease. So, cytogenetics actually grows out the pairs of cells. And so, that’s why that portion of the test can take a while to get back.

At our institution, it can take two to three weeks, because you’re actually growing out those cells to look at the chromosomes. And remember these are chromosomes, or genes, of the plasma cells. And so, we’re looking for those abnormalities that might be present. So, you think about it more for the biology of the disease.

When we’re looking at FISH, we’re also looking… That test shows a little bit different. It comes back quicker. It shows two different phases of cell changes.

And so, it will tell us about chromosomes as well. But do you have any additional chromosomes – so, that would make it a hyperdiploid narrow. It tells us if there’s a loss of a chromosome – so, you’re missing one, a hypodiploid. It also tells us about translocations – so, when you’ve had a piece of a chromosome change and go to another cell. And so, that, for instance, would be like that translocation t(11;14) or translocation t(4;14). So, it’s essential to have that testing to tell us about that, because it helps guide treatment. And as we talk more about targeted therapy, these things really can come into play.

Treatment Approaches in AML: Key Testing for Personalized Care

Treatment Approaches in AML: Key Testing for Personalized Care from Patient Empowerment Network on Vimeo.

When it comes to Acute Myeloid Leukemia (AML), genetic testing (or biomarker testing) is essential in helping to determine the best treatment approach for YOU. In this program, AML expert, Dr. Naval Daver reviews key decision-making factors, current AML treatments and emerging research for patients with AML.

Dr. Naval Daver is an Associate Professor in the Department of Leukemia at The University of Texas MD Anderson Cancer Center. More about Dr. Daver here.

Download Program Resource Guide

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Confused About AML Genetic Testing and Treatment? What You Need to Know

Transcript:

Katherine:                   

Welcome to INSIST! AML. A program focused on empowering patients to insist on better care. Today we’ll discuss the latest advances in AML, including the role of genetic testing and how this may affect treatment options. I’m Katherine Banwell, your host for today’s program. And joining me is Dr. Naval Daver. Welcome, Dr. Daver. Thank you so much for being here. Would you introduce yourself?

Dr. Daver:                    

Hello. Yeah. Thank you very much, Katherine. It’s a pleasure to join this discussion and meeting. I’m the Associate Professor in the Department of Leukemia at the MD Anderson Cancer Center. I focus on the treatment of acute myeloid leukemia and MDS, including the development of a number of clinical trials that are using targeted therapies and immune therapies for this disease. And with the great and dramatic progress, we’re seeing in acute myeloid leukemia; I think it is now more important than ever for patients to be aware of the options and be able to select the most appropriate therapy with their physicians.

Katherine:                   

Before we get into the discussion about AML, a reminder that this program is not a substitute for seeking medical advice. Please refer to your own healthcare team. Dr. Daver, I know the field of AML research is advancing rapidly. Would you give us an overview of the current treatment types in AML?

Dr. Daver:                    

There has been dramatic progress in the treatment of acute myeloid leukemia, especially in the last three years. We’ve had eight new drugs approved for the treatment of acute myeloid leukemia. The most progress I think that has happened so far is in the identification of particular molecular mutations and targeting those mutations with targeted therapies.

The mutations that are most important right now and have target options for FLT3 mutations, F-L-T-3, and the drugs that have been USDA-approved for this are an agent called Midostaurin, which is a first-generation FLT3 inhibitor and combination chemotherapy.

And then, more recently, another agent called Gilteritinib, as a single agent in relapse refractory FLT3 AML. The other mutational group that is also very important, and therapeutically needs to be checked, is IDHN1 and IDH2. And there are now two IDH inhibitors, IDH1 inhibitor, Ivosidenib, and IDH2 inhibitor, Enasidenib, both of which have been approved by the United States FDA for relapse patients with IDH1, IDH2 mutations. So, I think it’s really critical now to check for particular molecular mutations and to appropriately add the particular targeted therapy or select the particular targeted therapy in patients who have the mutation.

The other major area of advancement, and probably, if not the most important breakthrough that has happened, is the development of a new drug called Venetoclax. This is a BCL2 inhibitor. It’s new in AML, but in fact, it has been used for many years in CLL, which is chronic lymphocytic leukemia.

And this drug, in combination with Azacitidine in the frontline setting in older patients with AML who are not good candidates for intensive induction, has shown very high response rates, almost 70 percent CR-CRi, which is more than double of the 20 to 25 percent we were getting with Azacitidine alone.

And it’s now been approved by the US FDA and, in my opinion, and many of the experts really is the new standard of care and should be used in all older patients who are not good candidates for intensive chemotherapy given both the very high response rates, as well as now mature data showing significantly improved overall survival and a good tolerability.

So, there are many other breakthroughs. But I think these targeted agents, and Venetoclax, probably are the most impactful today.

And we’re focusing a number of new combinations building around this.  

Katherine:                   

What are common mutations in AML?

Dr. Daver:                    

Yeah. So, the most common mutation in AML is F-L-T-3, FLT3 mutation. This is both prognostically important mutation, presence of an FLT3 in a newly diagnosed AML, has been shown in many large publications by the German Cooperative Group, British Cooperative Group, our group, and others, is associated with an inferior survival.

Also, now, on top of that, it is also a therapeutically important mutation in addition to having negative prognostic value because the addition of FLT3 inhibitors seems to dilute, to a large extent, the negative prognostic value.

So, we believe that if we can identify FLT3 mutations at FLT3 inhibitors, we can definitely improve the outcome of those patients. The second most common is what we call NPM1 mutation, and that tends to occur with FLT3. About 55 percent of patients with an FLT3 mutation will have a coopering NPM1.

NPM1 is very interesting. With NPM1 mutation is present on it’s own without a FLT3, it’s actually associated with favorable outcome. It’s a favorable prognostic marker. However, if NPM1 is present with a FLT3, and especially if the FLT3 has a high quantity, high allelic load, then the NPM1 loses its favorable impact. So, now we’re kind of moving beyond just; do you have one mutation or not, which is what we thought 10 years ago, to; well, yes, you have this mutation, but what about the core-occurring mutation and even beyond. What about the burden, or what we call the variant allele frequency of that mutation?

So, for good or bad and I think it’s good in the end because it’s going to improve the patient outcomes, that we are getting more, more in-depth and there’s no longer quote, unquote, AML.

So, there’s a lot more granularity and analysis that is required even before starting treatment. And this is the thing that, in the community, we’re educating the doctors a lot, is that it’s okay to wait four to six days, especially if the patient does not have a very proliferative leukemia, to get the important bloodwork to identify the appropriate molecular and chromosome group.

So, that we can select the right treatment which will improve outcome rather than just rushing into standard treatment and missing a particular molecular chromosome group.

Katherine:                   

True. It might not be – the genetic testing might not be right for everyone.

Dr. Daver:                    

Right. Right.

Katherine:                   

What is genetic testing in AML?

Dr. Daver:                    

So, genetic testing in AML is basically what we call molecular profiling.

So, it’s looking at the presence of particular molecular mutations. For example, at MD Anderson, we do what we call 81 gene panel. So, this looks at 81 different genes for mutations in the bone marrow of newly diagnosed acute myeloid leukemia. Now, how did we come up with 81 genes? So, this was actually done by literature analysis and review of previously published preclinical and translational studies, and we basically selected all mutations that had been shown to occur in two percent or more of thousands of AML patients. And we found 81 such mutations. So, that any mutation that had a two percent or higher frequency in known published or public databases was included.

And that’s how we’re able to analyze for the mutation. So, it’s still possible that there may be some very rare mutations that are present, and those may be important for research. But they don’t change our treatment decision today. And so that’s what we call genetic profiling. Some people call it molecular mutation analysis. Some people call it next-generation sequencing.

But basically, this is looking for mutations in particular genes that are known to occur in AML. Now of those 81 genes; and some people do a 100 gene panel, some do 50, so those are variables; but among those, there are four or five that are most important: the FLT3, as we discussed, where we can use FLT3 inhibitors; IDH1 and two, because we can use IDH1 and IDH2 inhibitors; TP53 is a very important mutation because it has very high risk and adverse prognosis.

And there are now new drugs coming that may be very effective in TP53. So, we are checking for that. Those drugs are in trials, but the trials are showing very promising data and could be a great option if a patient is known to have a TP53.

Those drugs are Magrolimab, CD47 antibody, and APR-246. So, these are the four most important therapeutic mutations.

There are also some mutations that have prognostic value even though we cannot target them. These include mutations like RUNX1, DNMP3A, ASXL1.

One does not need to know the list. But the point is that these mutations may help determine whether a patient falls into intermediate-risk group or high-risk group, which then impacts the decision as to whether we need a stem cell transplant or not. So, it really is important to get this molecular profiling. It’s actually available in the United States commercially. And any clinic or hospital is able to actually order it. And insurance will cover it in 100 percent of the cases.

Katherine:                   

Wow, that’s great. What should – when should patients be tested, and how is testing done?

Dr. Daver:                   

Yeah. So, the basic testing for any suspected new acute leukemia is to get a bone marrow biopsy. That has to be done.

That should be done very quickly because all of the information that will be generated to make the treatment decision will come off the bone marrow biopsy.

Katherine:

What about retesting, Dr. Daver? Is that necessary?

Dr. Daver:                    

Yeah. So, retesting is necessary in – not for everything, I think.

But let’s say someone had treatment induction and relapsed a year later. So, we would definitely retest: 1) to confirm with the bone marrow’s relapsed AML, get the blast percentage because we need that before restarting treatment, so we know what was the starting point to know how the patients doing after treatment if he’s responding. 2) Molecular testing, for sure, should be repeated. We usually repeat the molecular testing such as FLT3, IDH1, IDH2, because there are drugs that can target these mutations in a relapse.

And more interestingly, we actually have published, and other groups have also published, that there are some patients who may not have those mutations at baseline but may actually acquire or have detectible mutations at relapse. So, if you don’t have FLT3 at baseline, your physician may assume that the FLT3 is not there, not do mutational testing. But in fact, that may not be true. So, it is important to retest about 15 percent, one five percent, in our publications can acquire a detectible FLT3. Which is critical because this could then change your treatment.

IDH1 and two are rarely lost or acquired, but we have seen a few five percent or so cases of that. So, it’s still better to check for that. And then TP53 we check for because now we have these new research clinical trials, phase one, two, that are showing some very encouraging activity in TP53. So, these are probably the main things to retest for.

There’s also some new clinical data emerging with a new drug called menin inhibitor that targets a particular chromosome abnormality, MLL rearrangement. This is again in a phase one setting, so the data may not be widely disseminated. But we’re seeing some very encouraging activity with menin inhibitors.  

And so, we are 100 percent checking for the MLL rearrangement chromosome, which can be done on FISH, or routine chromosome.

And if that is there then trying to get on one of the menin inhibitor trials, they’re opening about 25, 30 centers with different menin inhibitors, would be a very, very good option because we think these will be the next molecular or chromosome-targeted breakthrough in AML.

Katherine:                   

We’ve been discussing how molecular testing results lead to targeted therapy. How do targeted therapies work?

Dr. Daver:   

Targeted therapy means that we’re targeting a particular mutation. Now we may be targeting in different ways. So, some of the drugs, like FLT3 inhibitors, these are the most established and oldest targeted therapies in acute myeloid leukemia, been in development for about 18 to 20 years, work by blocking a particular receptor, the FLT3 receptor.

That receptor, when blocked, removes the growth and proliferation signal to the leukemia blast. And that receptor is much more preferentially and heavily expressed on the surface of the acute myeloid leukemia cell as compared to the normal, healthy myeloid or lymphoid cell. So, basically, we are shutting down the growth signals, resulting in eventual death of the leukemia blast and that’s how FLT3 inhibitors work. So, it’s a more of a direct activity resulting in cell death over a few days and quick action. On the other hand, we have what also is called targeted therapies but act very differently. These are IDH1, IDH2 inhibitors.

So, when you use an IDH1 or two inhibitor, they do go to the IDH1 and two receptor on the surface of the acute myeloid leukemia cell, but actually, they don’t result in the death of the cell. They actually cause what we call differentiation.

So, they promote that immature abnormal leukemia cell to undergo maturation and become a normal myeloid cell, which, over time, will die because normal cells have a finite lifespan, and they will die. As compared to leukemia blasts, which can live on much, much, much longer. And so, this process is called differentiation. So, FLT3 inhibitor, very different direct cell death. IDH inhibitor, very different from most maturation differentiation of immature cells to mature cells and takes longer. So, this is important clinically because with FLT3 inhibitors. We see responses quickly, one to two months. IDH inhibitors it takes longer, three to five months.

And so, targeted therapy is not one and all the same. You may be targeting a particular receptor, but the modality of action downstream may be very different.

Katherine:                   

What’s the treatment regimen for targeted therapies, and how long are patients treated with these types of therapies?

Dr. Daver:   

Yeah. I mean, that’s an area of big research. There’s no one field of answer yet for – and I don’t think there will be.

Of course, eventually. So, it really depends on; 1) What setting we’re using it in? Newly diagnosed, relapsed AML. In relapsed AML, with most targeted therapies, whether you’re use is a single agent, like FLT3, IDH1, IDH2, TP53, MLL-targeted agents, the goal is to get a patient to transplant.

Transplant, meaning allogeneic stem cell transplant using a sibling donor or a match-generated donor.

Because in relapsed AML without transplant, irrespective of the genetics and chromosomes, all relapsed AML have very poor outcome. The survival is only 20 percent or less without transplant.

If we can get a patient to transplant, we do have a good chance of long-term survival. So, the goal is transplant. And we usually use a targeted therapy for short, finite period, two to four months, to get a remission, get to transplant, hope that will cure the disease.

In front line, it’s quite different. We’re using induction chemotherapy with FLT3 inhibitors. In some research trials, we’re adding IDH1 and two inhibitors. We’re using Venetoclax, which is a kind of a targeted therapy.

Also, the BCL2 in combination with hypomethylating agents. And here, the targeted therapy is often used indefinitely. At least for one or two years. But in our approach and our guidelines, we continue the FLT3 inhibitor, IDH1 or two inhibitor or Venetoclax, as long as patient is tolerating it and does not have disease progression.

So, these are being used kind of similar to CML, chronic myeloid leukemia, where we use tyrosine kinase inhibitors or myelofibrosis, where you use jak inhibitors. They don’t cure the disease, but they continue to control the disease as long as you take them.

And in the end, we call this functional cure.

If somebody takes a FLT3 inhibitor and lives 20-plus years, semantically, he was never a cure, like an infection gets cured. But functionally, to me, he lived a normal life, and he was cured.

Dr. Daver:                    

And so, that’s how we’re using those inhibitors in the frontline setting different from the relapse setting.

Katherine:                   

How do these newer therapies differ from more traditional chemotherapy?

Dr. Daver:   

Yeah. Dramatically different. Completely different from traditional chemotherapy. So, to put it in more layman terms, traditional chemotherapy is like a nuclear bomb. Right? You – There’s a lot of things there in the marrow. You don’t know what’s good. You don’t know what’s bad. Blow it all up and hope that, when the new plants grow, the good ones grow and the bad ones were kill. And, in fact, this is true, to a large extent. Traditional chemotherapy, not to put it down, is actually been curative in a large population of AML for the last three decades. Our group and British MRC and Polish, and many groups have published up to 50 to 65 percent cure rates, especially in younger patients, below 65, with traditional chemotherapy.

So, this is not bad. People always get depressed with leukemia. But if you look at solid tumors, I mean, they have never achieved cure rates above 10 to 15 percent till the last decade or so. So, we were still getting 60, 65 percent cure rate. Two out of three.

So, traditional chemotherapy has done great work. But it was that approach. Just nuclear explosion. Take it all out, and hope good stuff comes.

Now the targeted therapy’s like a sniper. It’s actually looking for the particular leukemia cells and trying to take them out one by one with minimum collateral damage to your healthy bone marrow cells, which are important to produce red cells, platelets, white cells. So, guess what? There’s much less toxicity. You don’t see the hair loss with these agents. You don’t see the mouth sores and mucositis. GI complications are much less; infection risk is usually less.

Not to say they don’t have their own side effects. Unfortunately, even the targeted therapies have unique side effects. But, in general, those side effects are much less impactful in a negative quality-of-life way and much more manageable and tolerable. So – And, in the end of the day, they’re actually often more effective.

So, for example, with the FLT3 inhibitor, the study that was done with Gilterinib and Quizartinib, two very potent FLT3 inhibitors, was looking at a single-agent FLT3 inhibitor versus three-drug, high-intensity combination nuclear chemotherapy. And if I told this to any layperson, they would say, oh my God, that’s completely unfair comparison. You’re going to use three drugs, IV chemo, strong chemo, and compare it to one oral targeted pill. There’s no way the pill can be even equal, leave apart, win.

But guess what? The targeted therapy actually won. It not only was equal. It doubled the response rates, it reduced the toxicities and early mortality and led to improved overall survival, the gold standard. So, this shows that even though they are sniper, they can actually be much more effective with less toxicity. So, it’s a win-win. Better, tolerable, and more effective. Now the next stage within then decade, we think, it’s not one or the either, it’s really a combination. So, we’re reducing the dose of chemotherapy. So, we’re not making it as nuclear as it was. It’s still intense. But much more tolerable. And we’re compensating for that by adding the targeted therapy.

And, in fact, in the end, we expect much higher responses and survival with much better tolerability and lower early mortality. But I don’t think we’re at a stage where traditional chemotherapy is gone. Maybe 10, 12 years from now, as many more developments come, we’ll get there. But I think it still has a role, especially in the younger AML patients.

Katherine:                   

Dr. Daver, you mentioned the – some common side effects of chemotherapy. What about some of the newer therapies? Do they also have side effects?

Dr. Daver:                    

Yeah. Absolutely. I mean, every therapy we have in leukemia has a side effect. There’s no drug I can mention that is just devoid of them. Of course, some are less, and some are more. So, to be more specific, I think, for example, IDH1, IDH2 inhibitors, these are probably one of the most tolerable treatments we have in all of leukemia treatment. In general, they don’t cause much myelosuppression. Meaning, drop in blood counts. They don’t cause hair loss. They don’t cause mouth sores and GI upset in majority of people.

They’re always some patients who may. But what they can cause are two things: Number one, is they can cause what we call the differentiation syndrome.

And differentiation syndrome means the blasts that are going from the immature state to the mature state; in that process, they can cause an inflammatory reaction. And this can manifest with fever and cough, and chest pain, hypoxia. It’s something that’s actually very, very easily treatable, giving steroids for three or four days will take care of it. But many times, people were not aware of this. And so, often, we saw this was missed in the community.

So, that’s one specific example. With the FLT3 inhibitors, sometimes we see that they can cause more prolonged drop in blood counts, and count recovery can be delayed. Or we can sometimes see that they may cause some cardiac signals; increase in cardiac intervals. Again, something that, with close monitoring, bloodwork, keeping the electrolytes normal, can be managed. But I don’t want to go through the whole list. But the point is that there are specific and unique side effects that can be seen with particular targeted therapies.

And again, this is a learning curve where we have done these trials for eight to 10 years. So, we became familiar. But when the drug is approved, it’s a – it’s kind of a night-and-day situation in the community. They didn’t have the drug yesterday. They have it today. But there may not be any learning curve there. So, I think that’s where a lot of education and interaction with our colleagues is now coming into play.

But also, patients, I think, need to take this a little bit into their own hands, and also read about the label, read about the drug. So that, if they have side effects, if they actually ask their doctor and say, do you think this could be differentiation? I read about it. Yeah, most people will at least think about it. And I think this could be helpful to make sure that things are not missed. So, we do want patients to be more interactive and kind of  take things into their own hand. Because there are so many new drugs out there that their doctors may not be fully familiar yet.

Katherine:                   

Well, let’s talk about patient advocacy. What are some of the key tests that patients should ask for after they’ve been diagnosed?

Dr. Daver:                    

Yeah. Absolutely. So, I think the key things that patients should want to get the information is: 1) Knowing the bone marrow blasts.

I mean, that’s really basic. Just knowing what leukemia it is. What are the blast percentage? 2) Is, I think, chromosome analysis is very critical to get that information and to make sure we’re not missing acute promyelocytic leukemia, or core-binding factor leukemia, which have different treatments and very favorable outcomes, and would never, in general, never require a allogenic transplant. At least in majority of cases.

And 3), which is the one where we still see that it may sometimes not be available or be missed, is molecular testing.

I think it’s very critical to request molecular testing. And among molecular testing, especially FLT3, maybe IDH1 and IDH2, and TP53.

So, I think these are the most important data sets. Cytogenetics, key molecular mutations, bone marrow blasts, and confirmation of the type of leukemia before we embark on any treatment.

Katherine:                   

How can patients feel confident, do you think, in speaking up, and becoming a partner in their care?

Dr. Daver:   

Yeah. I mean, this is always a touchy area because physicians may feel that this is kind of encroaching on their territory or telling them what to do. And this is always a major challenge. I think when you go for the clinic visits, just to have a list of your questions written down and having them prepared and prioritizing them.

I always say, have your top-three questions ready.

We’ll try to do the others. But we’ll do the top three. And I think, when you have a new diagnosis of AML, the top three should be: what is the type of leukemia I have, and what are the bone marrow blasts? Number one. Do we have any chromosome and molecular information? Number two. And number three: Are there any specific treatments for my specific AML based on that chromosome molecular information? Or do we need additional information, and can we wait for that safely? I think these are the three very reasonable questions which, I think again, most leukemia experts will automatically be discussing this.

But, I think, for a patient, I think that’s important information to make sure they get before proceeding. If there’s time, the fourth question will be: Is – Are – Do we have a choice between high intensity, low intensity? And if we do, what are the pros and cons? In some cases, there may be a choice. In some cases, it may very clear that high intensity is the way to go, or low intensity is the way to go. But still, I think it’s often good to discuss that with your physician.

So, these are probably the four things one can bring up reasonably without the physician feeling that this is going to take forever, and I cannot discuss this. And then a lot of the AML treatment happens in-patient. So, there will be a lot of time for additional discussion. I tell my patients that, look, once we get the basics and the treatment decided, which is what we do in clinic, then you’ll be in the hospital most of the time. If it’s induction chemo for four weeks. Even if it’s Venetoclax, often they’re admitted for five to seven days, they will have more time then to discuss with the physician, the nurses, on a daily basis, and get more of the nitty-gritty.

Things like diet, exercise, lifestyle. Can I meet friends? I think you should not try to bring those things up right in the first visit. Because that may dilute the key information. So, I think staggering it, keeping in mind that many physicians are extremely busy, and getting that information in pieces over time, is probably productive for you and for the doctor.

Katherine:                   

With Covid-19 affecting all our lives right now, what should AML patients be considering at this time?

Dr. Daver:   

There’s a lot of guidelines on general approaches to managing things in COVID. And all of those guidelines heavily center, as we would think intuitively, on precautions.

Hand washing, minimizing contact, avoiding crowded places, trying to get treatment, potentially locally, if there are equivalent options available. We have not changed any of our frontline – we discuss this a lot every week in our faculty meeting.

This is discussed especially, as you know, because Houston currently is a major center affected heavily by COVID, and so, we have discussed whether we should move in a universal way to lower-intensity therapy for all patients. And we haven’t. And there’s pros and cons to that. When we do induction chemotherapy higher intensity, we, in fact, admit our patients for 28 days.

o, actually, even though it’s high intensity, the patient is more protected because they are in the room. Isolation rooms, sometimes. And they have minimum contact with outsiders. So, with COVID, actually, there’s very little opportunities or chances for them to get it. But the chemo is intensive. So, if they did get COVID, then it could be much more difficult or risky, or even fatal. On the other hand, low-intensity therapy is good because it’s low intensity and the risk of COVID, the frequency may or may not be changed; we don’t know. But the intensity we think could be lower because the immune system has not been suppressed.

However, low-intensity therapy very often is given outpatient. And so, then you have the benefit of lower intensity but the risk that you are going to be driving back and forth to the medical center, getting bloodwork, exposed to people in the waiting room, this and that. So, what we decided, after a lot of discussion among a big leukemia expert faculty in our group, was that we will still decide the optimum treatment based on the leukemia chromosome, molecular, age, fitness of the patient like we’ve always done.

And then we just have to try to encourage the patients to do as much precautions as possible. The other thing with the COVID, I think is very important is that, even though you may not be able to travel to your academic institution nearby because it’s harder to travel now, it’s still a good idea to try to get a consultation. We are doing a number of phone or email consultation, either directly with the patient, and even more frequently with their community doctor.

So, I get every day, four or five emails from academic even, and community physicians just saying, I have this patient, new AML, relapsed AML, whatever the case may be, here’s the mutation chromosome information, and I was going to do this. But the patient asked that I run this by one of my top academic colleagues. So, maybe MD Anderson. Some, I’m sure, are talking to Sloan. Some are, I know, are talking to Dana Farber. Cornell, whatever it may be. So, you can always request that. And maybe 100 percent of physicians may or may not do that.

And we’re seeing this collaboration actually. One of the positive things of COVID is we’re seeing these collaborations becoming better and better over time.

Katherine:                   

Oh, excellent. If a patient does need to go to clinic for a visit, what safety measures are in place?

Dr. Daver:   

Yeah. So, there’s a few things we’re doing in clinic is; one is we have staggered our clinics. So, instead of having everybody come at 9:00 or 10:00 a.m., and having 30 people in the waiting room, we really have more time slots.

And we ask people to come three of them at a time in the waiting room. We’re minimizing it three to five patients at most

Of course, there’s a lot of sanitization, dispensation units everywhere, encouraged to use those. The other important thing which, unfortunately, is a double-edged sword, is that we have had to minimize the number of friends, relatives, spouses, that can come with patients.

In fact, the policy at MD Anderson, like most cancer centers, is that nobody is allowed with the patient unless the patient is physically really impaired, as in wheelchair-bound or cannot go to the restroom. Of course, there are exceptions. But generally, I know, and I actually benefit a lot from it too, when patients have their family because the emotional support also helps our medical team to get information across. The patient may be sometimes stressed and forget things. So, what we’re doing more and more is doing phone calls.

So, what I would recommend is, as soon as doctor comes in, say, hey, doctor, can I call my daughter or my wife? I want her to listen to everything. Perfect. I don’t mind. There’s a speaker on. Good.

So, that helps with communication. But those are the big changes we have done from the clinic perspective. Still seems to be working relatively smoothly. We’re still seeing almost about the same number of patients in clinic that we were before COVID. And we have, fortunately, and knock on wood, not seen big numbers of leukemia patients with COVID. And we think the primary reason is because leukemia patients are just very cautious from the beginning. Even before COVID, they knew the risks, and we want them to continue that as much as possible.  

Katherine:

Dr. Daver, thank you so much for joining us today.

Dr. Daver:   

Thank you very much. Always a pleasure.

Katherine:

And thank you to all of our partners.

To learn more about AML and to access tools to help you become a more proactive patient, visit powerfulpatients.org. I’m Katherine Banwell – Thank you, Dr. Daver.

Ask Your Doctor About These Essential Genetic Tests for CLL

Ask Your Doctor About These Essential Genetic Tests for CLL from Patient Empowerment Network on Vimeo.

Genetic testing results can impact a chronic lymphocytic leukemia (CLL) patient’s treatment options and provide a deeper understanding into their disease. Dr. Steven Coutre, a CLL specialist, reviews essential tests and explains their role in CLL care.

Dr. Steven Coutre is a Professor of Medicine in the Hematology Department at Stanford University Medical Center. Learn more about this expert here.

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Transcript:

Dr. Steven Coutre:

In terms of testing for CLL, additional testing, of course, diagnostically, it’s generally not a challenge. It’s very straight-forward. A test that we call Flow Cytometry on a blood sample is usually sufficient to establish the diagnosis. Very, very uncommonly would a bone marrow exam be needed, for example. And in routine practice, also, we don’t necessarily give CT scans to establish a diagnosis or even to, as people say, stage the disease. It really isn’t necessary in most cases.

However, we do have a staging system that correlates with the extent of the disease and that’s simply based on our exam and blood counts, but people also want more information. They wanna know how they’re gonna do, specifically. So, we can add additional tests, genetic testing as people often call it, that can further subdivide individuals into groups that give you additional information on how you might do, meaning if you’re without symptoms, and an observation is recommended, you wanna know, “Well, how long is it gonna be before I need treatment?” Although our staging system gives that information, we can refine that further.

One test is the so-called FISH test, which looks at specific chromosome abnormalities, and the second test that’s generally used is called the IGHV Mutation Assay. That’s really looking at what’s called the mutational status of your immunoglobulin genes. So, it’s really those two broad categories that are most relevant.

Now, we don’t necessarily advocate doing that testing on everyone at the time of diagnosis. Certainly, not everyone who is without symptoms, where we’ve already decided that treatment is not indicated. So, as you can imagine, you can do that testing. You might come up with a profile that’s less favorable. And then, instead of the watch and wait approach, or as folks like to call it, “watch and worry approach,” you worry even more. But then, of course, if you have a favorable profile, then you’re happier. You’re more pleased.

However, we don’t do anything differently regardless of what those tests show, at least at current state. Compared to a decision that’s already been made about treat or not treat. We do, however, strongly advocate getting that testing at the time of treatment, and sometimes, repeating some of the testing with subsequent treatment, when you require treatment, say, a second time, in some cases. So, very important to have a discussion about these tests and what information you will get from them.

Well, we’ll often see patients who are coming for another opinion about their disease. Perhaps they’ve been recently diagnosed, and they have been advised for observation, so, it’s, of course, natural to ask whether that’s a reasonable approach. And in that context, other testing often comes up in the conversation. Perhaps they had the testing done, the FISH, and the mutational testing, and they wanna know what it means, or actually we see some results that have been obtained and we ask them about it. And there’s very often confusion, or really lack of information about what they mean.

So, we really try to discuss that issue. That issue of testing with each and every patient, whether or not they’ve had it done, really trying to let them know what it means. That way they’re fully informed, and in some cases, people feel very strongly that they would like to have it done, even through they realize that we’re not gonna act on it at that point. So, I think pretty much for all patients, it should be part of the initial discussion.

Again, in terms of genetic testing are these tests that I discussed. It’s important to understand what information they give you so you understand why your physician may be making a distinction between one therapy versus another. It is very, very important to get that testing, if somebody is talking about using chemotherapy, for example, hopefully. That’s quite uncommon. But with our newer agents, we know that they work broadly despite those other features.

Nevertheless, I think it’s important for a patient to at least expect the discussion about these tests. We’re not asking you to go to your physician and ask that they be done in all cases, but really understand perhaps why your physician recommended that they not be done at that particular time. 

Advocate for These CLL Genetic Tests

Advocate for These CLL Genetic Tests from Patient Empowerment Network on Vimeo.

Genetic testing results can influence a chronic lymphocytic leukemia (CLL) patient’s treatment options and provide a more in-depth understanding into their disease. Dr. Philip Thompson, a CLL specialist, reviews key tests that CLL patients should advocate for.

Dr. Phillip Thompson is an Assistant Professor in Medicine in the Department of Leukemia at The University of Texas MD Anderson Cancer Center. Learn more about this expert here.

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Transcript:

Dr. Philip Thompson:

I would say that I see a lot of patients that have previously seen an oncologist closer to home and then traveled to MD Anderson for a second opinion. And so, I can say that over the last three or four years, there’s definitely a significant change in the awareness of physicians in general about doing genetic testing for CLL.

So, in particular, almost everybody will get a FISH test, which I didn’t always see three or four years ago. And more patients are now having IGHV mutation status analysis done. The thing that I see that is very rarely done, though, is what we call next-generation sequencing, or NGS, that looks for mutations in individual genes, and most importantly, in the TP-53 gene that I mentioned.

So, I would – and the other thing that often isn’t done is what we call a carrier tag, which is a routine analysis of the chromosomes of the CLL cells. And it requires some special techniques for the lab to get it to work in CLL. But that can actually provide additional information compared to just FISH.

So, I would suggest to a patient, particularly if they’re gonna do a bone marrow biopsy on you, which is an invasive procedure, that you really try to get some clarity around what tests are going to be ordered on that beforehand. And if you’ve just been diagnosed and you’ve got early-stage CLL, you can make an argument about how many of these tests are absolutely necessary to start with. Because the biggest utility in these tests is in determining what type of treatment you’re going to have.

If you’re not immediately going to have treatment, they don’t necessarily change what your oncologist is going to do. They’re going to monitor you over time and see if your disease is getting worse or not. But I still think they’re useful to have the – a lot of them are useful, particularly the IGHV mutation status and FISH are useful to have at initial diagnosis. Because they give you a really good idea of what the biology of this disease is – this patient’s disease is like and how quickly they’re likely to progress, and that may change how frequently you monitor the patient.

But anyway, I would say it’s important to ask them what genetic testing you are gonna get. And that you ask – have an understanding of what can be ordered.

 And in particular, if you’re going to get treatment, you must ask for TP-53 sequencing, FISH for 17-P deletion, and IGHV mutation status because those three things are essential to determine the optimal treatment that you have. And you shouldn’t feel shy about asking, are those things going to be done.