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.

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

What Are Essential Genetic Tests for Metastatic Breast Cancer Patients?

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

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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.

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

Related Resources:

 

How Genetic Mutations Affect Metastatic Breast Cancer Disease Progression and Prognosis

Metastatic Breast Cancer: Debunking Common Misconceptions

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.

Breast Cancer Before 40: What You Should Know

Breast Cancer Before 40: What You Should Know from Patient Empowerment Network on Vimeo.

Dr. Stephanie Valente reviews key information for women under the age of 40 with breast cancer, including risk, treatment approaches and the role of genetic testing.

Dr. Stephanie Valente is the Director of the Breast Surgery Fellowship Program at Cleveland Clinic. More about this expert here.

Related Program:

Breast Cancer Before 40: How Can I Preserve My Fertility?


Transcript:

Sure. So, when we talk about breast cancer in young women, usually we are referring to women under the age of 40. And the prevalence for breast cancer in general is one out of eight women. For women under the age of 40, it’s about a seven percent incidence of breast cancer. So, it’s about a seven percent incidence in the general population in the United States. So, that’s about 12,500 women per year are diagnosed under the age of 40 with breast cancer.

So, the prevalence has pretty much been the same over the years. We used to think that women diagnosed at a younger age had a more aggressive breast cancer. But the more we look at things, the more we realize that women under the age of 40 usually are diagnosed at a later stage because it’s not something that somebody in their 20s or 30s is thinking that a breast lump equates to cancer. So, these women unfortunately present at a later stage.

Many times, it’s because they are pregnant, breastfeeding or just not having any family history where the first thing they think of when they get a lump is that they actually have breast cancer.

So, the first thing is women under the age of 40 usually present at a later stage, meaning that they have larger cancers, and the cancers because they are larger have had more time to spread to the lymph nodes. So, these women they don’t necessarily have more aggressive breast cancers than older women, it’s just that it’s found at a later stage.

So, the treatment options are the same for young women with breast cancer. So, depending on the size of the tumor and the size of her breast, women are given the option for a lumpectomy which usually is follow by radiation versus a mastectomy. And studies have shown that either surgical choice is a good option for women. And that one surgery doesn’t make a young woman, or an older woman live any longer.

That the survival for breast cancer is based on stage not the choice of surgery that they pick.

So, one of the first things is that women under the age of 50 – the average age for breast cancer in the United States is between 64 and 68.

So, if you are under the age of 50 or under the age of 40 there’s a higher chance that maybe these women carry a gene that would increase the risk of getting breast cancer. And so nowadays, we test over 21 genes. But these genes can increase their risk of getting breast cancer not only in the breast they have the breast cancer in, but in their other breast as well. It also increases the risk for other types of cancers such as ovarian cancer. And they could potentially pass this gene on to their kids.

So, sometimes women – and this is the great thing about academic medicine. Everything is changing so quickly with the modern research. So, a lot of times a woman who is triple negative, which is an estrogen receptor negative breast cancer.

If they are genetic positive for the BRCA gene, they qualify for certain medications or chemotherapy that we know targets specifically that type of cancer and their gene. So, that’s why it is important for some of these women to get genetic testing to see if the certain chemotherapy regimens or medicines that we have would benefit their type of cancer.

So, one of the things for any woman diagnosed with breast cancer at a young age is to offer those women genetic testing. And sometimes it can be a relief or sometimes it can be very challenging for these women to think, “Oh my gosh. I have this gene. I’m at increased risk for more cancers.” And that potentially they could pass that on to their children.

So, having the women who come in meet with a genetics counselor to go over the risks. And the reality is that of all the women under the age of 50 that test for the gene, only 10 percent actually carry the gene.

So, the good thing is that 90 percent most likely don’t have the gene. But it still is an anxiety provoking thing for these women to go through.

Another thing is that these women a lot of times are younger. So, they have either two things – young children to take care of which is extremely difficult to mange an already stressful motherhood. You throw in a diagnosis of cancer, whether or not there is a dad involved or a father that needs to help out with these kids. A lot of times their families need to help out. So, we have a psych oncologist that’s part of our team. And it’s really great. How do you tell your kids you have cancer? And how do you manage kind of day-to-day life with going through this? So, that’s another great program that is offered. And importantly for a woman who doesn’t have children but maybe desires to have children or even to have more children than the ones that she has,
looking at fertility options for young women is huge.

So, we know that some of the chemotherapy that we give breast cancer patients decreases their ability to have children in the future. So, the chemotherapy can shut down the ovaries. So, sometimes women – and this is the great thing about academic
medicine. Everything is changing so quickly with the modern research. So, a lot of times a woman who is triple negative, which is an estrogen receptor negative breast cancer.

If they are genetic positive for the BRCA gene, they qualify for certain medications or chemotherapy that we know targets specifically that type of cancer and their gene. So, that’s why it is important for some of these women to get genetic testing to see if the certain chemotherapy regimens or medicines that we have would benefit their type of cancer.

So, the one thing is that I tell these women that breast cancer takes a good year between chemotherapy if they need it, surgery, radiation of they need it and the whole process of recovery. That is really takes a good solid year before they are kind of done going to their doctor’s appointments. But the reality is that for an early stage breast cancer, studies have show for young women the overall survival is over 92 percent. So, I say, “This is going to be a tough year. We are going to get through this together. And the good thing is that you are going to be alive in five, 10, 15, 20 years. And so, our goal is to get you the best quality of life not only now but in the future.”

As far as hope for young women with breast cancer, things are changing so fast. The medicine that’s out there – we’re doing these studies where women are getting chemotherapy and by the time they get to surgery about 40 to 60 percent of the tissue that I take out has no residual cancer. That’s phenomenal. That means that the medications that these women are getting are working really well for their cancer. And so, the hope is that in 10 years I don’t have a job because the medicine that they are getting works so well that the cancer can be removed without needing surgery. And so, I think in our lifetime we will find either a cure or a complete resolution of breast cancer.