BC Treatment & Clinical Trials Archives

When it comes to breast cancer treatment, patients and their care partners have much to consider. Some people may seek breast cancer treatment and clinical trials, others may have few feasible options. Understanding treatment options, goals, and what to expect are vital to achieving the best possible outcome for you.

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Barriers to Clinical Trial Participation

 

What are some of the barriers to clinical trial participation? What is a virtual clinical trial? Should my doctor be speaking to me about my clinical trial options? Dana Dornsife, founder of Lazarex Cancer Foundation, speaks to the key barriers in trials and how COVID-19 has really opened the door for a lot of opportunity to engage with patients around clinical trials.

Barriers to Clinical Trial Participation

Barriers to Clinical Trial Participation from Patient Empowerment Network on Vimeo.

What is a Virtual Clinical Trial?

What is a Virtual Clinical Trial? from Patient Empowerment Network on Vimeo.

COVID and Clinical Trials

COVID and Clinical Trials: Has There Been a Shift? from Patient Empowerment Network on Vimeo.

What Should You Know About the Role of Surgery in Breast Cancer Treatment?

What Should You Know About the Role of Surgery in Breast Cancer Treatment? from Patient Empowerment Network on Vimeo.

Dr. Stephanie Valente explains how surgery approaches, including mastectomy and lumpectomy, are used in treating breast cancer, and addresses common misconceptions about mastectomy.

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

See More From The Pro-Active Breast Cancer Patient Toolkit

Related Resources:

 
 

Transcript:

Dr. Valente:            

So, breast cancer patients have the option to remove their whole breast, which is called a mastectomy. And if they pick that option, they could choose to have reconstruction or to essentially go flat. Yes, we have even done reconstruction in metastatic breast cancer patients. Metastatic breast cancer patients live for a really long time, so giving them reconstruction to make them feel whole and kind of put them back together after a mastectomy is definitely a good option.        

The other option is to just remove the cancer. So, if the patient has a small breast cancer, and it’s metastatic, we can just say – Hey, you don’t have to have the whole breast removed. So, we can do a lumpectomy, as well.

So, a lumpectomy is essentially a surgery that removes the cancer with a normal rim of tissue around it. We also call it a partial mastectomy, meaning you’re removing just part of the breast. Or it’s also called breast-conserving surgery. So, it’s any method that removes that cancer with a normal rim of healthy tissue around it but allows the woman to keep her breasts.

So, when it comes to surgical choices and a cancer coming back, some women think that if they pick the most advanced surgery, such as a mastectomy, it helps prevent cancer from going somewhere else in the body. And that’s actually not true. Removing both breasts, doesn’t make you live one day longer. At that point, a mastectomy or a lumpectomy is a choice.

And prognosis – meaning whether or not the cancer’s gonna show up somewhere in the body – is based really on two things – the stage at which the breast cancer presents itself and what type of breast cancer it is – meaning is the cancer outside of the lymph nodes? How large is it? And if it’s a triple negative or some other type of breast cancer? Those determine the higher likelihood that somebody could develop metastatic breast cancer later in their life, even though small, early-stage breast cancers, unfortunately, can also develop metastasis later on in life.

But women sometimes think that if they pick the most aggressive surgery, it’s helping prevent metastatic spread later on in life. And that’s actually not the choice.  Breast cancer surgery is the option that women choose to surgically remove their breast cancer. But again, choosing a mastectomy or a lumpectomy for an early-stage breast cancer is a choice of how they wanna remove the breast cancer. But it doesn’t improve the chances that they won’t have metastatic spread later on.

So, the role of surgery for metastatic breast cancer is mainly for what we call to remove the cancer or sometimes for local control. So, the number one treatment if somebody is diagnosed with metastatic breast cancer is systemic therapy. That might be chemotherapy or endocrine therapy. But it’s really to get the metastatic disease under control.

So, where does breast cancer usually go? Bones, liver, lungs, brain. So, surgery to remove the breast or the breast cancer in the breast doesn’t really take care of those problems. But a lot of times for metastatic cancer, the one reason would be for local control. So, if the cancer is causing issues in the breast – swelling, coming out of the skin – where it’s a wound issue, then we’ll remove that to get better control of the area in the breast.

The other reason is if somebody has metastatic cancer, and their cancer in the other area of their body is controlled with the therapy, then we say – Hey, chemo’s working, or the systemic therapy’s working. The only thing that seems to be left is the area in your breast. Then for a conversation with medical oncology, we say you don’t have to come off your medications. This is a good time to remove the breast cancer to control that problem.

Metastatic Breast Cancer Treatment and Research News

Metastatic Breast Cancer Treatment and Research News from Patient Empowerment Network on Vimeo.

As metastatic breast cancer testing approaches continue to expand, new and promising treatments have emerged. Dr. Lisa Flaum shares information on recently approved treatment options and the role of genetic markers in accessing targeted therapy. 

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

See More From The Pro-Active Breast Cancer Patient Toolkit

Related Resources:

 

Transcript:

Dr. Flaum:                  

There are a lot of new and promising treatments for metastatic breast cancer. So, the treatments in general and the novel treatments and studies really vary based on the subset of metastatic breast cancer. So, when we’re making our treatment decisions, a lot of it is defined by those markers. So, if someone has a tumor that is hormone receptor, estrogen and progesterone receptor positive, and HER2-negative, the mainstay of treatment is typically drugs that target estrogen and often partnering drugs that target estrogen with other more novel or newer treatments.

So, just in the last five plus years, there have been a number of new drugs and even new drug categories that we didn’t have previously. So, for that population of the estrogen receptor positive tumors, the biggest breakthrough over the last number of years has been a class of drugs called CDK4/6 inhibitors. So, that includes drugs like Ibrance, Kisqali, Verzenio. And they’ve emerged as a very important and effective and often a recommendation for our first-line treatment for these patients combined with anti-estrogen therapies that have vastly improved outcomes for patients. So, a much higher percentage of patients respond to these drugs, the duration of the responses has extended quite a bit. And importantly, patients tend to tolerate this drug class really, really well.

 So, for many patients starting out with that diagnosis, this type of drug class is going to be part of the discussion. Even in the last year, another drug category has emerged with approval of a new drug called alpelisib, which is something called at PI3 kinase inhibitor. So, again, back to defining the options based on the molecular profile of the tumor. So, this newer oral drug also partnered with anti-estrogen therapy, has been an important breakthrough for the treatment of patients who harbor this specific molecular abnormality. So, important to define whether that’s an option by some of these molecular testing.

There’s also newer drugs and studies of newer drugs that affect the estrogen receptor in different ways than some of our traditional medications.

And this is an ongoing area of significant research. So, that’s the estrogen receptor positive tumors.

For patients who have HER2-positive tumors, these are tumors that tend to be more aggressive, that tend to require more aggressive upfront treatment, which usually involves drugs that specifically target HER2. So, again, defining what’s driving the tumor and hopefully having drugs available that can target that specific abnormality. So, HER2 targeted drugs have evolved quite a bit over the last couple of decades.

Initially, we just had a drug called Herceptin and then a drug called Perjeta or pertuzumab was developed. Then more recently a drug called Kadcyla. And then even in just the last six to 10 months, two new drugs that target that HER2 protein. One of them is called tucatinib, the other one is called Enhertu. They’re not necessarily appropriate for the first line of treatment, but really sort of expands our toolbox in terms of how we treat these types of tumors. And these are developments that have occurred, for one of the drugs, just in the last six months, and the other within the last year. So, a lot of progress.

And then for the third subset of tumors, which are the triple-negative tumors, those are the ones that do not over-express estrogen, do not have estrogen or progesterone receptors, and don’t overexpressed HER2. This has been historically an area of unmet need. So, tumors where we can’t use anti-estrogen therapies, we can’t use HER2 targeted drugs. And so, the main stay has always been chemotherapy. And even for this subset, we’ve had progress.

So, one of the drug classes that’s been approved in the last couple years for triple-negative breast cancers is immunotherapy. So, immunotherapy has gotten a lot of press. It’s been really breakthrough treatment for a lot of different cancers, has lagged behind to some degree in breast cancer, but has become now one of the early treatment options for people with metastatic disease, specifically those that harbor a molecular marker, an immune marker, something called PD-L1. So, another example of the tumor’s biology dictating potentially one of the treatment options.

There have been other drugs that have been approved for triple-negative breast cancers in women who have BRCA mutation, so who have germline genetic predisposition to breast cancer. And that opens another array of treatment tools that have been approved in the last few years. And then more recently, just over the last six months, another drug that’s been approved for triple-negative breast cancer, which is a drug called sacituzumab, again, not first treatment, but something that defines potentially future lines of treatment. So, big picture, there has been a lot of progress that increasingly alters our treatment tools for patients and allows us to have sequential treatments that can be effective if their given treatment is no longer effective.

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.

See More From The Pro-Active Breast Cancer Patient Toolkit

Related Resources:

 

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?”

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

Related Resources:

 

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.

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

Related Resources:

 

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.

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.

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

Related Resources:

 

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.

When Is a Full Mastectomy Appropriate for Metastatic Breast Cancer Patients?

When Is a Full Mastectomy Appropriate for Metastatic Breast Cancer Patients? from Patient Empowerment Network on Vimeo

Dr. Stephanie Valente discusses mastectomy for metastatic breast cancer patients, including common misconceptions around breast cancer surgery.

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

See More From INSIST! Metastatic Breast Cancer


Transcript:

Dr. Valente:                

So, there are a lot of reasons that a woman undergoes a mastectomy. The first one is choice. So, anytime somebody is diagnosed with breast cancer, they actually have the choice of whether or not they want to remove their whole breast. So, even if their cancer is small, they do have the option of removing the whole breast. If the cancer is smaller, they might have the option to save the breast, which is called a lumpectomy.

Sometimes cancer is found, and it’s a little bit more advanced where saving the breast is not an option. So, the cancer is larger than a lumpectomy would allow. And sometimes that’s what’s called the extent of disease. So, the amount of breast tissue that’s involved requires a majority of the portion of the breast to be removed.

So, just because a woman has breast cancer that’s made its way out of the breast, into the lymph nodes, or beyond – so, metastatic cancer – doesn’t necessarily mean that she needs a mastectomy. So, just because you’ve got metastatic cancer doesn’t necessarily mean that the breast needs to be completely removed.

So, I think that one of the biggest misconceptions is that the more aggressive somebody is with their surgery, the better their chances with survival.

And again, taking a step back and saying you can choose a more aggressive surgery, but a more aggressive surgery doesn’t necessarily mean it gets you out of chemotherapy or it gets you out of radiation therapy. Those things are recommended, independent of a woman’s choice for the type of surgery that she may or may not pick.

Understanding Metastatic Breast Cancer Resource Guide

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Metastatic Breast Cancer: Accessing the Best Treatment For YOU

Metastatic Breast Cancer: Accessing the Best Treatment For YOU from Patient Empowerment Network on Vimeo.

How could genetic testing results impact your metastatic breast cancer treatment options? In this INSIST! Breast Cancer webinar, Dr. Julie Gralow discusses essential testing, the latest targeted therapies and emerging breast cancer research.

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.

Download Program Resource Guide


Transcript:

Katherine:

Welcome to Insist Breast Cancer, a program focused on empowering patients to take an active role and insist on better care. Today, we’ll discuss the latest advances in metastatic breast cancer, 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. Julie Gralow. Welcome, Dr. Gralow. Would you introduce yourself?

Dr. Gralow:   

Hi, thanks, Katherine. I’m Dr. Julie Gralow. I’m 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.

Katherine:    

Excellent, thank you. Before we begin the discussion, a reminder that this program is not a substitute for seeking medical advice. Please refer to your own healthcare team. Well, Dr. Gralow, let’s start by helping people understand how breast cancer is staged. Could we go through those stages?

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.

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 – 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.

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 do 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:

So, it’s something that patients live with.

Dr. Gralow:  

Right.

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.

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.

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 gonna 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.

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.

Katherine:    

For patients who may be hesitant to speak up – to advocate for themselves in the process – I’m gonna start again. For patients who may be hesitant to speak out for themselves and advocate for their own care and treatment, what advice do you have?

Dr. Gralow:   

You have a whole team who’s behind you, and I’m the MD on the team, but I’ve got a nurse practitioner, and a nurse, and a scheduler, and a social worker, and a nutritionist, and a physical therapy team, and financial counselors. I’ve got a whole team who works with me. And so, a patient might be hesitant to speak up during the actual appointment with their physician. It’s a short amount of time. I would recommend come into it with written-down questions because things go fast. You don’t get a lot of time with your doctor.

Things go fast, but don’t come in with 25 questions, either. Pick your top few that you want to get taken care of this visit because if you come in with 25 or 30, you’re gonna lose the answers to most of them. Maybe bring somebody with you who’s an advocate and a listener for you who could be taking notes, so you can process and you don’t have to write it down, or ask if you can record it. It’s really important if you’re newly diagnosed or maybe there’s a progression and you’re going on a new treatment. That’s okay too.

But, I would also say you have a whole team behind you, so sometimes, if you don’t have time or if you’re hesitant to speak up in your doctor’s visit, you can ask the nurse, or maybe you can ask the social worker for help, even. See if there’s support groups around.

Interestingly, we’ve got a peer-to-peer network where patients can request to talk to somebody else who’s matched to them by some tumor features, and their stage, and things like that. Maybe finding somebody else who’s gone through something similar, and somebody independent to talk to instead of relying on your family.

It can also be really helpful to talk to a therapist or a psychologist about your fears, and sometimes, you want to be strong for your family, strong for your children and all, but you need a safe space with somebody that you can just express your fears and your anger if that’s what’s going on, or your depression or anxiety to while you’re trying to hold a strong face for others in your family. So, I would encourage patients to look at who is the whole team and talk to the other members of the team as well, and sometimes, they can help advocate.

Also, find somebody who might be able to come to your appointments with you, somebody who will help you advocate or remind you – “Didn’t you want to ask this question?” – or be another set of ears that you can process it with afterwards.

Katherine:     

Dr. Gralow, we’ve covered a lot of useful information today for patients. Thank you so much for joining us.

Dr. Gralow:    

Thank you, Katherine.

Katherine:       

And, thank you to all of our partners. To learn more about breast cancer and to access tools to help you become a proactive patient, visit powerfulpatients.org. I’m Katherine Banwell.

Confused About Immunotherapy and Its Side Effects? You Aren’t Alone

“You don’t look like you have cancer.”

More than one patient undergoing immunotherapy to treat cancer has reported hearing statements like that. Immunotherapy is one of the recent advances in cancer treatment that belie the stereotypes about the effects of cancer treatment. 

The side effects of immunotherapy are different from those associated with chemotherapy and radiation. However, that does not mean immunotherapy does not have side effects. Patients and care partners need to be aware of these potential side effects and to be vigilant in addressing them with their oncologists because they can signal more serious complications if left untreated.

What is Immunotherapy?

Despite the increase of immunotherapy treatment options in recent years and considerable media attention paid to advancements in this field, there remains confusion about immunotherapy and its side effects. Many cancer patients are unaware of whether immunotherapy treatments are available for their specific diagnosis. Others don’t know that genetic profiling of their tumors is usually required to determine if immunotherapy is an option and not all treatment centers routinely conduct genetic profiles of tumors. A  survey by The Cancer Support Community found that the majority of patients who received immunotherapy knew little to nothing about it prior to treatment and were unfamiliar with what to expect.

Immunotherapy works by manipulating the patient’s immune system to attack cancer cells. It is perceived as gentler and more natural than chemotherapy and radiation, without the same destructive effect on the body’s healthy tissues.  This, combined with a lack of prior understanding of immunotherapy, can lead patients and care partners ill-prepared for possible side effects.

Furthermore, immunotherapy is a category of therapies, not a single type of treatment. There are a variety of immunotherapy drugs, most of which are administered via infusion.  Side effects will vary by drug, the cancer and its location, treatment dose, and the patient’s overall health.

The following are the most common types of immunotherapy.

  • Checkpoint inhibitors use drugs to block proteins in the patient’s immune system that would otherwise restrain the immune system, often referred to as taking the “brakes” off the immune system.
  • CAR-T therapy modifies the patient’s T-cells in a lab to enhance their ability to bind to cancer cells and attack and kill them.
  • Oncolytic virus therapy uses genetically modified viruses to kill cancer cells.
  • Another therapy uses cytokines (small proteins that carry messages between cells) to stimulate the immune cells to attack cancer.

Immunotherapy can be part of combination therapy. It might be combined with chemotherapy. It might be used to shrink a tumor that is then surgically removed.  Or multiple immunotherapy drugs might be used simultaneously.

What Are The Side Effects?

With immunotherapies, side effects typically occur when the immune system gets too revved up from the treatment. The most common side effects for immunotherapy treatments are fatigue, headache, and fever with flu-like symptoms. Some people also experience general inflammation often in the form of a rash. Many melanoma patients report blotchy skin discoloration, called vitiligo, during treatment. These milder side effects can usually be managed with over-the-counter remedies and adjustments to daily activities.

For checkpoint inhibitors, the fastest growing segment of immunotherapy treatments, mild side effects occur in 30% – 50% of patients. Serious side effects typically occur in less than 5% of patients. (See “Understanding Immunotherapy Side Effects” from the National Comprehensive Cancer Network and the American Society of Clinical Oncology.)

Less common side effects are blisters, joint pain, thyroid inflammation, and colitis (inflamed colon resulting in diarrhea with cramping). Some patients who receive CAR T-cell therapy develop a condition known as cytokine release syndrome, which causes fever, elevated heart rate, low blood pressure, and rash. 

In rare cases, immunotherapy has resulted in lung inflammation, hepatitis, inflammation of the pituitary, and detrimental effects on the nervous and endocrine systems. In most cases, the conditions clear up when treatment ends.  However, there have been outcomes in which immunotherapy caused diabetes or tuberculosis.

“Overall there are fewer side effects [with immunotherapy],” explained Dr. Justin Gainor, a lung and esophageal cancer specialist at Mass General during an Immunotherapy Patient Summit hosted by the Cancer Research Institute. “But the immune system can affect anything from the top of the head down to the toes. Any organ has the potential to be affected.”

As the application of immunotherapy has expanded, so has our understanding of the potential side effects. Like most medical treatments, how one person responds to immunotherapy can be different from another even when the cancer diagnosis and drug therapy are the same.

The essential thing patients and care partners need to know about side effects is they should always be reported to their oncologist or nurse oncologist.

Why Patients Should Talk to Their Provider About Immunotherapy Side Effects

Because immunotherapy has created newer therapy options, there isn’t the volume of experiences as with older treatments. The infinite number of variables that patients provide once a treatment moves beyond clinical trials and into the general patient population generate more diverse outcomes.  And, as most therapies are less than 10 years old, there hasn’t been an opportunity to study the long-term effect of these therapies. This is why oncologists advise patients and their caregivers to be extra vigilant in noting any changes experienced during and after treatment.

Many side effects are easy to treat but medical providers want patients to be forthcoming in discussing any and all side effects. This is in part to improve understanding of side effects, but also because a mild cough or a case of diarrhea might be harbingers of a more systemic issue that will grow worse if left untreated.

Patients should not be hesitant to discuss side effects because they fear they will be taken off immunotherapy.  Sometimes a pause in treatment might be necessary, but the earlier the oncologist is made aware of a side effect, the less likely that will be necessary.

In addition, patients undergoing immunotherapy should always take the name(s) of their immunotherapy drugs and the name of their oncologist when seeing medical professionals outside of their cancer treatment team. This is especially important when visiting the ER.  Because immunotherapy drugs are newer and highly targeted to certain cancers, many medical professionals remain unfamiliar with drug interactions and treating related side effects.

Immunotherapy On The Rise

Immunotherapy treatments have resulted in reports of remission in cases that would’ve been deemed hopeless just five or 10 years ago.  The Federal Drug Administration (FDA) has approved various immunotherapy treatments for melanoma, lung cancer, head and neck cancer, bladder cancer, cervical cancer, liver cancer, stomach cancer, lymphoma, breast cancer, and most recently bladder cancer.  (Here is a list of  immunotherapies by cancer type from the Cancer Research Institute.)

“It’s revolutionized how we treat our patients,” says Dr. Gainor of Mass General about immunotherapy’s impact on lung and esophageal cancer.

Advances in immunotherapy research and trials continue to generate optimism and excitement. A clinical study in Houston is looking at using immunotherapy to prevent a recurrence. Researchers in Britain recently announced a discovery that might lead to advances in immunotherapy treatments to a much broader array of cancers.

While there is excitement around the field of immunotherapy and it has resulted in unprecedented success in treating some previously hard-to-treat cancers, it remains an option for a minority of cancer diagnoses.  It works best on solid tumors with more mutations, often referred to as having a high-mutational load or microsatellite instability (MSI) high. And it is not universally successful for every patient.

With hundreds of clinical trials involving immunotherapy alone or in combination with other therapies, it is certain more treatment options are on the horizon. As more therapies are developed and more patients with a greater variety of conditions undergo immunotherapy, we will also increase our understanding of potential side effects.

Side effects should not dissuade patients and care partners from considering immunotherapy if it is available or from advocating for genetic tests to deteimine if it is an option. Many patients undergoing immunotherapy have previously undergone chemotherapy and report that the side effects are fewer and milder by comparison.  The important thing is that patients and their partners know what to expect and communicate with their treatment team.

If the next 10 years in immunotherapy research and development are anything link eth elast 10, we can expect more exciting advancements in the battle against cancer. For more perspective on what’s ahead for immunotherapy see the Cancer Research Institute’s article: Cancer Immunotherapy in 2020 and Beyond.

Breast Cancer Treatment and Side Effects

This was originally published by breastcancer.org here.


In recent years, there’s been an explosion of life-saving treatment advances against breast cancer, bringing new hope and excitement. Instead of only one or two options, today there’s an overwhelming menu of treatment choices that fight the complex mix of cells in each individual cancer. The decisions — surgery, then perhaps radiation, hormonal (anti-estrogen) therapy, and/or chemotherapy — can feel overwhelming.

Breastcancer.org can help you understand your cancer stage and appropriate options, so you and your doctors can arrive at the best treatment plan for YOU.

In the following pages of the Treatment and Side Effects section, you can learn about:

  • Planning Your Treatment: What types of treatment are available, the most likely sequence of treatments, treatment options by cancer stage, and fitting treatment into your schedule.
  • Getting a Second Opinion: Reasons for getting a second opinion about your treatment plan, how to go about getting one, and what to do once you’ve got it.
  • Surgery: Breast-conserving surgery (lumpectomy), mastectomy, and lymph node dissection, and what to expect from each. Also included: Prophylactic surgery and breast reconstruction.
  • Chemotherapy: How chemotherapy works, who should get it, different types and combinations, and side effects and how to manage them.
  • Radiation Therapy: How radiation therapy works, who it’s for, advantages, side effects, and what to expect when you get it.
  • Hormonal Therapy: The link between hormones and breast cancer and how different groups of drugs — including ERDs, SERMs, and aromatase inhibitors — can affect that link. Also covered: Side effects of hormonal therapies.
  • Targeted Therapy: How different drugs work, who should get them, how they’re given, side effects, and major studies.
  • Immunotherapy: What is immunotherapy, different types of immunotherapy, and who it’s for.
  • Complementary and Holistic Medicine: How complementary medicine techniques such as acupuncture, meditation, and yoga could be a helpful addition to your regular medical treatment. Includes research on complementary techniques and ways to find qualified practitioners.
  • Drugs for Treatment and Risk Reduction: A reference list of drugs used to treat and reduce the risk of breast cancer, including how they work, to whom they are typically given, and side effects.
  • Treatments for Pain: Ways to treat cancer- and treatment-related pain, including types of medications and tips on talking to your doctors about pain.
  • Treatment Side Effects: A reference list of side effects and ways to manage them.
  • Lymphedema: All about lymphedema, including who is at risk, what to watch out for, how to reduce risk of lymphedema flare-ups, and how to find a lymphedema therapist.
  • Clinical Trials: What clinical trials are and how they work, why they’re important, and how to find trials that may be appropriate for you.

A New Standard of Care for HER2-Positive Metastatic Breast Cancer?

This podcast was originally published by Dr. Rashmi Murthy on December 11, 2019 on breastcancer.org here.


Dr. Rashmi Murthy, assistant professor of breast medical oncology at the University of Texas MD Anderson Cancer Center in Houston, discusses the results of the HER2CLIMB study that she presented at the 2019 San Antonio Breast Cancer Symposium showing that the experimental medicine tucatinib offers benefits to people diagnosed with HER2-positive metastatic breast cancer and may be a new standard of care.

Listen to the episode to hear Dr. Murthy explain:

  • A summary of the study results
  • Why this study included people with brain metastases
  • The side effects of tucatinib
  • Why she thinks the results are practice changing

Understanding Clinical Trials: A Jargon Buster Guide

When it comes to cancer treatment you or a loved one may be considering participating in a clinical trial as a treatment option.  Clinical trials are designed to evaluate the safety and effectiveness of a treatment. They may involve researchers administering drugs, taking blood or tissue samples, or checking the progress of patients as they take a treatment according to a study’s protocol.

Learning about clinical trials can be a steep learning curve – not least because the process comes with a lot of new terms, acronyms and jargon.  To help you, I’ve put together this list of the most common terms you will find when you are researching clinical trial information. This is not an exhaustive list but it is a helpful starting point. At the end of this article you will see links to find more information.

Adverse Effects (AE)

Also called Adverse Events, or Adverse Drug Reaction, AEs are any harmful event experienced by a person while they are having a drug or any other treatment or intervention. In clinical trials, researchers must always report adverse events, regardless of whether or not the event is suspected to be related to or caused by the drug, treatment or intervention.

Arm

Subsection of people within a study who have a particular intervention.

Bias

Bias is an error that distorts the objectivity of a study. It can arise if a researcher doesn’t adhere to rigorous standards in designing the study, selecting the subjects, administering the treatments, analysing the data, or reporting and interpreting the study results. It can also result from circumstances beyond a researcher’s control, as when there is an uneven distribution of some characteristic between groups as a result of randomization.

Blinding

Blinding is a method of controlling for bias in a study by ensuring that those involved are unable to tell if they are in an intervention or control group so they cannot influence the results. In a single-blind study, patients do not know whether they are receiving the active drug or a placebo. In a double-blind study, neither the patients nor the persons administering the treatments know which patients are receiving the active drug. In a triple-blind study, the patients, clinicians/researchers and the persons evaluating the results do not know which treatment patients had. Whenever blinding is used, there will always be a method in which the treatment can be unblinded in the event that information is required for safety.

Comparator

When a treatment for a specific medical condition already exists, it would be unethical to do a randomized controlled trial that would require some participants to be given an ineffective substitute. In this case, new treatments are tested against the best existing treatment, (i.e. a comparator). The comparator can also be no intervention (for example, best supportive care).

Completed

A trial is considered completed when trial participants are no longer being examined or treated (i.e. no longer in follow-up); the database has been ‘locked’ and records have been archived.

Control

A group of people in a study who do not have the intervention or test being studied. Instead, they may have the standard intervention (sometimes called ‘usual care’) or a dummy intervention (placebo). The results for the control group are compared with those for a group having the intervention being tested. The aim is to check for any differences. The people in the control group should be as similar as possible to those in the intervention group, to make it as easy as possible to detect any effects due to the intervention.

Efficacy

How beneficial a treatment is under ideal conditions (for example, in a laboratory), compared with doing nothing or opting for another type of care. A drug passes efficacy trials if it is effective at the dose tested and against the illness for which it is prescribed.

Eligibility Criteria/ Inclusion and Exclusion Criteria

Eligibility criteria ensures patients enrolling in a clinical trial share similar characteristics (e.g. gender, age, medications, disease type and status) so that the results of the study are more likely due to the treatment received rather than other factors.

Follow-up

Observation over a period of time of participants enrolled in a trial to observe changes in health status.

Informed Consent

A process (by means of a written informed consent form) by which a participant voluntarily agrees to take part in a trial, having been informed of the possible benefits, risks and side effects associated with participating in the study.

Intervention

The treatment (e.g., a drug, surgical procedure, or diagnostic test) being researched. The intervention group consists of the study participants that have been randomly assigned to receive the treatment.

Investigator

A person responsible for the conduct of the clinical trial at a trial site. If a trial is conducted by a team of individuals at a trial site, the investigator is the responsible leader of the team and may be called the principal investigator (PI).

Multicentre Trial

A clinical trial conducted according to a single protocol but at more than one site, and therefore, carried out by more than one investigator.

Number needed to treat (NNT)

The average number of patients who need to receive the treatment or other intervention for one of them to get the positive outcome in the time specified.

Outcome Measures

The impact that a test, treatment, or other intervention has on a person, group or population.

Phase I, II, III and IV Studies

Once the safety of a new drug has been demonstrated in tests on animals, it goes through a multi-phase testing process to determine its safety and efficacy in treating human patients. If a drug shows success in one phase, the evaluation moves to the next phase

  • Phase 1 tests a drug on a very small number of healthy volunteers to establish overall safety, identify side effects, and determine the dose levels that are safe and tolerable for humans.
  • Phase II trials test a drug on a small number of people who have the condition the drug is designed to treat. These trials are done to establish what dose range is most effective, and to observe any safety concerns that might arise.
  • Phase III trials test a drug on a large number of people who have the condition the drug is designed to treat. Successful completion of Phase III is the point where the drug is considered ready to be marketed.
  • Phase IV trials can investigate uses of the drug for other conditions, on a broader patient base or for longer term use.

Placebo

A fake (or dummy) treatment given to patients in the control group of a clinical trial.  Placebos are indistinguishable from the actual treatment and used so that the subjects in the control group are unable to tell who is receiving the active drug or treatment. Using placebos prevents bias in judging the effects of the medical intervention being tested.

Population

A group of people with a common link, such as the same medical condition or living in the same area or sharing the same characteristics. The population for a clinical trial is all the people the test or treatment is designed to help.

Protocol

A plan or set of steps that defines how something will be done. Before carrying out a research study, for example, the research protocol sets out what question is to be answered and how information will be collected and analysed.

Randomized Controlled Trial (RCT)

A study in which a number of similar people are randomly assigned to 2 (or more) groups to test a specific drug, treatment or other intervention. One group has the intervention being tested; the other (the comparison or control group) has an alternative intervention, a placebo, or no intervention at all. Participants are assigned to different groups without taking any similarities or differences between them into account. For example, it could involve using a computer-generated random sequence. RCTs are considered the most unbiased way of assessing the outcome of an intervention because each individual has the same chance of having the intervention.

Reliability

The ability to get the same or similar result each time a study is repeated with a different population or group.

Sample

People in a study recruited from part of the study’s target population. If they are recruited in an unbiased way, the results from the sample can be generalised to the target population as a whole.

Subjects

In clinical trials, the people selected to take part are called subjects. The term applies to both those participants receiving the treatment being investigated and to those receiving a placebo or alternate treatment.

Trial Site

The location where trial-related activities are conducted.


References

The Canadian Institutes of Health Research (CIHR)

TROG Cancer Research

ICH.org

NICE

Further Resources

American Society of Clinical Oncology’s Cancer.Net trials site

National Cancer Institute (NCI) Clinical Trials lists open and closed cancer clinical trials sponsored or supported by NCI. 

ClinicalTrials.gov database of privately and publicly funded clinical studies

CenterWatch Clinical Trials Listing