Tag Archive for: fertility

What Are Treatment Options for Endometrial Cancer?

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What Are Treatment Options for Endometrial Cancer? from Patient Empowerment Network on Vimeo. 

What endometrial cancer treatment options are currently available? Endometrial cancer expert Dr. Emily Ko shares an overview of options, including chemotherapy, surgery, radiation, targeted therapies, combination therapies, hormonal therapies, and discusses considerations for patients who are trying to preserve their fertility.

Dr. Emily Ko is a gynecologic oncologist and Associate Professor of Obstetrics and Gynecology at the University of Pennsylvania. Learn more about Dr. Ko.
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Transcript:

Katherine:

I’d like to talk about the treatments that are currently available. You mentioned chemotherapy, but what else is available for people? 

Dr. Ko:

Absolutely. So, treatment for endometrial cancer is usually some combination of surgery, and then it may be followed by possibly chemotherapy, as well as radiation, and sometimes, it may be a combination of all three treatments, or sometimes, it’s a combination of one or two of those, depending on the exact stage, depending on the exact cell type, and some of the other factors. 

Katherine:

Are hormonal therapies used as well, and targeted therapies? 

Dr. Ko:

Yes. 

Katherine:

I know they are in other cancers. 

Dr. Ko:

Yes. And so, I think the question is where do those come into play? So, I would say the usual algorithm most commonly would be that surgery is done first, as the most common first step, and then, based on the information obtained from surgery and the pathology report that comes from that, then there’s usually some type of a recommendation about should there be a second stepped treatment, and that frequently can be chemotherapy/radiation.  

Now, the areas where targeted therapy – for example, immunotherapy – where does that come in? So, that now has come into the – I would call it the second stage. We’re combining it with the classic chemotherapy drugs – Taxol-carboplatin, for example. That’s one example where it could come into play. Another example could come into play where a patient had gone through classic Taxol/paclitaxel and carboplatin, then had cancer come back, and so, that could be another instance where that pembrolizumab or pembro with lenvatinib (Lenvima) combination can be used in the setting of recurrence. 

Now, we could also say, hey, if your cancer type has those hormonal receptors present or is some type of what we call endometrioid histology, and we think that hormonal therapy may be more effective in that case, then that could also be used in a setting where the cancer has kind of grown again, the cancer has grown back, or actually, there are certain situations where patients, for example, may not undergo a hysterectomy. 

And, there are unique cases and those situations where patients are still trying to preserve their fertility, and therefore not wanting to undergo a hysterectomy, or they’re unable to undergo surgery safely. And so, in some unique situations, we may also use hormonal therapy as the mechanism to treat their cancer, and whether that is by way of a pill, whether that is by way of a progesterone intrauterine device, IUD, that is placed into the uterus, we also have situations where we tailor the therapy to the condition of the patient. 

Katherine:

When treating more advanced endometrial cancer disease in general, are the treatment options different than if you were treating somebody who had stage I or stage II, for instance? 

Dr. Ko:

Sure, great question. So, for some patients with, say, stage I, surgery alone is enough. 

For some other patients, subcategories of stage I, where we call them more high/intermediate-risk patients, they’re stage I, but there are a few features about their pathology that might make them slightly higher risk for recurrence – in those cases, we might consider a little bit of radiation after surgery, what we call adjuvant radiation or what we call radiation vaginal brachytherapy. Just three short treatments of a little bit of radiation to the top of the vagina has been shown to possibly decrease chance of recurrence in that area with very minimal side effects. 

So, that would be more commonly in line with stage I. There are some subtypes that can still be what we call high-risk, even in stage I/stage II uterine serous carcinoma, uterine carcinosarcoma. In those cases, we might also recommend chemotherapy along with some vaginal brachytherapy following their hysterectomy, so that’s the early stage. 

And then, with the advanced stage, yes. So, frequently, it’d be surgery first to secure the diagnosis, followed by some type of – it might be primarily chemotherapy, or it could be combination chemotherapy with radiation. And over time, I would say our paradigm for what we use for chemotherapy and radiation has changed a little bit.  

If you go back a couple decades, I think radiation was used a lot – whole pelvic radiation, even just without any chemotherapy. And then, we then had more data from research clinical trials, GOG-258 or PORTEC-3, that then had given us evidence that perhaps doing chemotherapy with some combination of radiation is going to be beneficial, or even moving towards primarily radiation could be a very good option in terms of long-term benefit/long-term survival. 

And, of course, that brings us to the present day, those two trials that I mentioned from ASCO, the GY018 and the RUBY, now bringing in the immunotherapy component to the chemotherapy, so there has definitely been an evolution to managing advanced stage. 

What I Wish I Knew Before My AML Diagnosis

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What I Wish I Knew Before My AML Diagnosis from Patient Empowerment Network on Vimeo.

AML patient and Empowerment Lead, Sasha Tanori, shares what she wishes she knew and what to ask before her AML diagnosis, and the importance of advocacy.

See More from [ACT]IVATED AML

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Transcript: 

Sasha Tanori:

So, one of the biggest things I wish I knew, especially before, was the whole saving your eggs type thing for fertility. That’s one of the biggest things that I honestly really regret because here it is almost what…five, six years later, and I, unfortunately, am infertile, so it really does suck because that was something that I was really looking forward to in my life was like being a parent or being a mom, and at the time, it’s just like…everything happened so fast, it was like, Okay, we’re going to…We did the chemo, and now we’re going to do a couple more rounds and then it’s like, Oh, we found a donor, so you could have your bone marrow transplant…oh my gosh, I can’t say the word, your bone marrow transplant. I think I had mentioned it to my doctor, but he was like, “Well, if we wait, now we’re going to lose the person who’s going to donate to you.” And I was like, “Okay, well, we need to hurry up and get that done, get it over with.

So back then, I really wish I would have advocated for myself more, ask more questions and because thinking back, I’m like, I don’t mind if I would have waited until after having my eggs frozen to find another donor, I think that possibly there could have been someone else out there.

But I think it was just in such of that state of mind of like, “I need to hurry and get this done. It’s life or death, I’m going to possibly die type of situation.” But you know I’m like, “No, I think I would have been okay if I would have waited another month or so until after I froze the eggs.” But you live and you learn, and there’s not really much you can do about it now, unfortunately. But at the time, I really wish that I would have spoken up and advocated for myself more if I would have known that that was going to happen, because like I said, five years later infertile can’t really do anything about it, you know? Yeah, my life is saved, but I can’t have kids though, so you just kind of think it heartedly about it, but yeah, that’s one of the things I really wish I would have advocated for myself more about. For now, I think everything else has been kind of…it’s been good. I mean, I’ve taken it step by step, by day, you just got to put on your big girl panties or put on your big girl shorts, I guess you could say, and just continue going about your day, you gotta wake up, do your job, take care of your family, take care of your life.

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What Are the Treatment Options for Early Stage Breast Cancer?

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What Are the Treatment Options for Early Stage Breast Cancer? from Patient Empowerment Network on Vimeo.

Breast cancer expert Dr. Adrienne Waks reviews available treatment approaches for patients with early stage breast cancer and explains the role of sub types when choosing a treatment plan.

Dr. Adrienne Waks is the Associate Director of Clinical Research at Dana-Farber Cancer Institute. To learn more about Dr. Waks click, here.

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Transcript:

Katherine:

Well, let’s get into the specific treatment options that are available for breast cancer patients. Could you tell us about those?  

Dr. Waks:

So, fortunately, the answer to that question is enormous, because we have so many effective treatment options in breast cancer and generally our patients do very well in the long term when they are diagnosed with early stage breast cancer, so stage I or II or III breast cancer.  

That might involve the breast, it might involve the lymph nodes under the arm, but it hasn’t traveled anywhere else in the body. So I’ll set aside metastatic breast cancer and just talk about stage I, II, and III. 

So, as you may know, we think about as medical oncologists we completely separate treatment considerations for three different subtypes of breast cancer. Those are hormone receptor-positive, HER2-positive and then triple-negative. So, again, highlighting just important developments and not really the overall treatment planning for each of those subtypes, in ER-positive disease or estrogen receptor-positive disease hormonally-driven, estrogen-driven breast cancer – those are all sort of terms for the same thing, I think there have been a couple of important developments over the last few years.  

Probably the most important recent one is the new understanding and demonstration that the CDK4/6 inhibitor abemaciclib, the brand name of that drug is Verzenio. 

That drug when we administer it for two years after a patient has had their surgery and in conjunction with alongside the antiestrogen medicines; the antiestrogen medicines are usually done for a minimum of five years, when we add on to that the CDK4/6 inhibitor abemaciclib, we see that for women with higher risk disease, so maybe some lymph node involvement or a large tumor in the breast or both that the addition of the Verzenio, the abemaciclib seems to decrease their risk of recurrence of breast cancer a couple of years out. So, that’s been an important exciting development. 

Again, not for all women within early stage estrogen-driven breast cancer, but for a little bit more advanced early stage disease like lymph node involvement. You know, we’re obviously always looking for ways to reduce that risk of recurrence for women who have a little bit more risk at diagnosis and the addition of abemaciclib was an exciting and welcome addition to our toolkit there. 

In HER2-positive disease, which is about 20 percent of breast cancers overall, I think what the recent years have brought us is increasing understanding that in many cases we give women too much chemotherapy and that we need to be – so, here it’s less about adding on. Like the Verzenio example I was just talking about and more about individualizing and figuring out in whom and how we can pull back from sort of the kitchen sink approach that we take often to treating a HER2-positive early stage breast cancer and be more thoughtful and more personalized in the amount of treatment that we give women with HER2-positive breast cancer. 

The reason for that is that we’re basically 20 years into understanding that for HER2-positive breast cancers we can treat those cancers very effectively with anti-HER2 antibody drugs like trastuzumab or Herceptin. We didn’t even know that until 20 years ago. And so, Herceptin, trastuzumab and similar drugs have really revolutionized how effectively we can treat women with HER2-positive breast cancers. And so, at this point, it’s becoming more and more clear that we can really lean more on our arsenal of anti-HER2 targeted therapies like Trastuzumab. Pertuzumab (Perjeta) is another one and trastuzumab MTNC and TDM1 is another one. 

So, we have all these excellent smart targeted treatments for women with HER2-positive disease, but yet the standard of care is still to give all those good rational targeted treatments with a whole bunch of chemotherapy that comes with a lot of side effects. 

I think more and more we’re figuring out that we can lean more on our anti-HER2 treatments and require less of the really side effect heavy chemotherapy, but how do we do that thoughtfully? We obviously don’t want to undertreat anybody, so how do we do that thoughtfully? How do we pick out the women who only need the anti-HER2 treatment and can get away with less chemotherapy. I think that’s really what’s exciting in HER2-positive early stage breast cancer right is how do we individualize and take advantage of targeted agents that we have? 

And then finally, in the third subtype of breast cancer which is triple-negative breast cancer which accounts for about 10 percent of breast cancers, the most exciting development there clearly in the last year or so is the realization and the demonstration in randomized clinical trial that we can improve outcomes for those women if we give them not just chemotherapy but also chemotherapy combined with immunotherapy and specifically the immunotherapy agent called pembrolizumab or Keytruda. 

So, up until a year or two ago, the standard for a stage I or II or III triple-negative breast cancer was to get a multiagent chemo regimen and chemo was really the only type of option we had to treat those triple-negative breast cancer patients and now we know from a major important clinical trial called Keynote 522, that if we take a standard chemo backbone and add Pembrolizumab immunotherapy onto it, that we can help those women do better in the long term. So, that’s really a pretty new in the last one or two years standard of care for triple-negative breast cancer. 

And I guess the last thing I’ll say is not about one of those three subtypes of breast cancer but specifically for women with a BRCA1 or BRCA2 mutation associated with their breast cancer, which is a minority. It’s about 5 percent of breast cancer patients. Obviously, the proportion changes depending on your subtype of breast cancer and your age when you’re diagnosed, but for women who have a breast cancer associated with BRCA1 or 2 mutation and have a higher risk or early stage breast cancer. 

So, again, they have a number of lymph nodes involved or a big tumor in the breast or something like that, we now know that we can add on one year of the PARP inhibitor medication called olaparib or Lynparza to the postoperative treatment of those breast cancer patients in addition to whatever other treatment they got; the antiestrogen pills, the chemotherapy, or a combination of those two, and with the addition of olaparib or Lynparza for a year that we can again see better long-term outcomes for those patients and help them avoid recurrences. 

So, that’s not a majority of breast cancer patients but is a targeted treatment that we’re very excited about that definitely makes an important contribution to reducing risk for women with a BRCA1- or BRCA2-associated cancer or men for that matter. I’m saying women, but it could absolutely apply to men. 

How Is Metastatic Breast Cancer Treated?

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How Is Metastatic Breast Cancer Treated? from Patient Empowerment Network on Vimeo. 

Breast cancer expert Dr. Adrienne Waks discusses treatment approaches for metastatic breast cancer and explains how research is evolving.

Dr. Adrienne Waks is the Associate Director of Clinical Research at Dana-Farber Cancer Institute. To learn more about Dr. Waks click, here.

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Transcript:

Katherine:

What about people who have metastatic disease? What treatment advances are available for them?  

Dr. Waks:

Yeah. You know, I think that’s an incredibly important question and a totally different set of discussions than we have with women with early stage breast cancer and unfortunately and unacceptably at this point for a woman diagnosed with metastatic breast cancer still typically that can become a life-threatening diagnosis. 

So, it’s exceptionally important that we rapidly improve the treatment options that we have for women with metastatic breast cancer. Maybe everybody says this every year, but I think that this year, 2022, has been a particularly exciting year in terms of advances that we’re making in the treatment of metastatic breast cancer, really of all subtypes. I would say the most exciting class of drugs or type of drugs that’s coming out in breast cancer and in all malignancies honestly, is called antibody drug conjugates, which is to say an antibody. So, a molecule that’s targeted to some particular approaching on a cancer cell surface and then is attached to or conjugated to a chemotherapy molecule.  

So, the antibody is like a smart delivery system directly to the cancer cell for what’s call a payload, basically like a sort of action molecule or the killer molecule, which is the chemotherapy. 

Those kinds of antibody drug conjugants have made a huge impact in recent years in improving outcomes for women really with all subtypes of breast cancer, so that drug class I think is a very exciting one to watch in general. In terms of specific recent developments in metastatic breast cancer, so probably the biggest blockbuster development over the past year and really over just the past three months is the understanding that we can break out a subtype of metastatic breast cancer that we really didn’t even talk about before which is called HER2-low breast cancer. So, before if you asked me in May of 2022, there really were only two types of HER2 readouts for a breast cancer tumor. 

There was a HER2-negative breast cancer tumor and there was a HER2-positive breast cancer tumor and as I already told you, the HER2-positive accounts for about 20 percent of breast cancers overall. The other 80 percent are HER2-negative. And so, historically, again you asked me three months ago I would have said if you’re HER2-positive and that 20 percent will give you these different HER2-directed treatments and if you’re not, we can’t use those. And what’s changed is that we’ve developed new antibody drug conjugants. So, drugs that are targeted against in this case the protein HER2 that seem to be so effective and work so well, that you don’t truly have to be HER2-positive.  

You can be HER2-low and still benefit from these treatments, which is to say your cancer has a little bit of HER2 protein on the surface of the breast cancer cells but not a lot. So, not enough to make it positive but enough to make it low in its designation. 

That’s actually a large proportion of breast cancer patients. It’s over 50 percent of breast cancer patients, so it’s significantly more than HER2-positive, so a large proportion of breast cancer patients actually fit into this new category called HER2-low and we now know from data that were presented in June of 2022 and then published in the New England Journal of Medicine, which is our biggest most high profile academic medical journal, we know that for patients who fall into that HER2-low category, again that’s more than 50 percent of breast cancer patients, that they can, if they have a metastatic breast cancer, benefit from this new antibody drug conjugate called trastuzumab deruxtecan (Enhertu).  

When it was compared to the existing chemo options we have for those patients which do have some efficacy but nonetheless, when trastuzumab deruxtecan was compared to the existing chemo options, it clearly looked better for patients with HER2-low breast cancer. So, that was not just an exciting advance in terms of new treatment options which we always love to be able to offer to patients but also in terms of breaking out this entirely new designation and subcategory that captures more than half of our metastatic breast cancer patients and helping us to offer them something new and hopefully will be a pathway for other drugs to be developed in this space and for this new subcategory. 

So, that was very exciting. I’ve been talking about it with patients all the time in the past just three months since those data came out.  

You know, a second antibody drug conjugate that has also been very exciting in recent months and recent years is called sacituzumab govitecan which Trodelvy is the brand name of that one. That’s an antibody drug conjugate that’s targeted against a different protein on the cell surface that’s targeted against the protein Trop-2, so that’s where the Trodelvy comes from. It’s targeting Trop-2. That’s an antibody drug conjugate that we’ve known for probably three or more years now can be very effective in triple-negative metastatic breast cancer. So, we’ve had that option for a number of years in metastatic triple-negative breast cancer. 

But again, just in the past few months have gotten good and exciting data that this Trodelvy or sacituzumab drug also works in estrogen-driven breast cancers.  

And so, it’s giving another option to patients with not just triple-negative but also estrogen-driven breast cancer. So, that was another very recent development just in the last three months or so. 

Katherine:

That’s really exciting. 

What Do You Need to Know About Metastatic Breast Cancer Genetic Testing?

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What Do You Need to Know About Metastatic Breast Cancer Genetic Testing? from Patient Empowerment Network on Vimeo.

Why is it important to ask about metastatic breast cancer genetic testing? Find out how test results could reveal more about YOUR breast cancer and could help determine the most effective treatment approach.

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Transcript:

Why should you ask your doctor about metastatic breast cancer genetic testing?

The National Comprehensive Cancer Network – also known as the NCCN – recommends that every metastatic breast cancer patient undergo genetic testing. The test results can help predict how your cancer may behave and could indicate that one type of treatment is more effective than another.

This testing identifies specific gene mutations, proteins, chromosomal abnormalities, and/or other molecular changes that are unique to YOU and YOUR breast cancer.

There are two main types of genetic tests used in breast cancer:

  • Germline or hereditary genetic testing, which identifies inherited gene mutations in the body. These mutations are present from birth, can be shared among family members and be passed on to subsequent generations.
  • The second is somatic or tumor genetic testing, which identifies markers that are unique to the cancer itself. It is also commonly referred to as genomic testing, biomarker testing, or molecular profiling. Somatic mutations are NOT inherited or passed down from family member to family member.
  • Depending on your history, your doctor may order one–or both–of these types of tests.

So why do the test results matter?

  • If you have specific gene mutations – such as the BRCA1 or BRCA2 inherited gene mutations – it could indicate that a targeted treatment approach may be the most effective option. For example, there are two oral targeted therapies that are approved specifically for use in metastatic patients with BRCA1-positive or BRCA2-positive breast cancer.
  • Results of these tests may also help you to find a clinical trial that may be appropriate for your particular cancer.
  • Additionally, results from germline genetic testing may suggest that close family members should also be tested to determine their risk.

How can you insist on the best breast cancer care?

  • First, always speak up and ask questions. Remember, you have a voice in YOUR breast cancer care.
  • Ask your doctor if you have had–or will receive–genetic testing, including germline and somatic testing.
  • If you have already undergone genetic testing, bring a copy of your results to your current doctor, so they can understand your results and determine whether additional testing is needed.
  • Have a discussion with your healthcare team about the test results – including which markers were detected and how results may impact your care and treatment plan.
  • Ask whether your family members should meet with a genetic counselor or undergo testing to help gauge their risk of developing breast cancer.
  • And, finally, bring a friend or a loved one to your appointments to help you process and recall information.

To learn more about breast cancer and to access tools for self-advocacy, visit powerfulpatients.org/breastcancer. 

Metastatic BC Research: How Can You Advocate for the Latest Treatment?

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Metastatic BC Research: How Can You Advocate for the Latest Treatment? from Patient Empowerment Network on Vimeo.

What do metastatic breast cancer patients need to know about the latest research news? Dr. Megan Kruse shares highlights from the 2020 San Antonio Breast Cancer Symposium (SABCS), along with her advice for advocating for the right testing to help guide treatment options.

Dr. Megan Kruse is a Breast Medical Oncologist at the Cleveland Clinic. More about this expert here.

See More From INSIST! Metastatic Breast Cancer

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What Could Advances in Breast Cancer Research Mean for You?

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Transcript:

Dr. Kruse:                   

At this year’s San Antonio Breast Cancer Symposium, there were a few interesting presentations about the treatment of first-line metastatic triple-negative breast cancer that I think patients should be aware of.

Two of the presentations centered around trials that were presented in the past. Those reporting, patients reported outcomes from the IMpassion 130 study, which looked at chemotherapy for metastatic triple-negative disease plus the immunotherapy atezolizumab. And then, there was also an update on the results from the KEYNOTE-355 study, which was a study again of chemotherapy for metastatic triple-negative patients in combination with pembrolizumab, a different immunotherapy. And both of these studies showed that there was benefit for women in certain sub-groups of triple-negative breast cancer when looking at addition of immunotherapy.

And so, what I’d like to draw patients’ attention to with these presentations is that you have to be aware of if you fall into one of these categories so you know if you’re a candidate for the particular type of immunotherapy that can be added to chemotherapy. There are two different ways to test for if a patient is a candidate for immunotherapy and they are both tests that can be done on biopsies of metastatic or cancer recurrent sites in the body.

They can also be sent off of original breast cancer tumors. And what we now know is that for patients who do not have markers that suggest immune activation or where the immune system would be responsive to immunotherapy the addition of that extra therapy really does not help to improve cancer control over chemotherapy alone. And I think that’s a really important topic because everyone is very interested in immunotherapy, but it does have side effects of its own and it can actually be lasting side effects in terms of inflammation in organs like the liver, the colon, and the lungs.

And then, the third presentation that I’d like to bring up is the IPATunity study, which looked at the addition of a targeted therapy called ipatasertib to, again, chemotherapy for the first treatment of metastatic triple-negative disease.

And so, this is getting into an area of targeted therapy for metastatic triple-negative disease. And again, only looks at patients that have a particular marker that suggests sensitivity to this drug. And those are certain genetic markers, predominately changes in a DNA marker called PIK3CA. In this study, we actually found that there was no benefit for the targeted therapy added to chemotherapy for patients that had that genetic mutation, which was different than what was seen in earlier studies of the same combination. So, I think there’s more work to be done and it’s probably too early to say that this targeted therapy will not be used in treatment of metastatic breast cancer.

But what all of these research studies show together is that metastatic triple-negative cancer is not really just one disease. It’s very clear that within that one name, there are multiple different patient types and tumor types that need to be cared for differently.

And so, again, I think the theme from these abstracts and these research presentations is that we have to look into the right therapy for the right patient at the right time, which largely involved DNA-based testing.

So, when patients are thinking about their treatment options and how to best help with their providers about what treatment options exist for them, I think it’s important to recognize the type of testing that may be advantageous in your cancer type.

And so, for all metastatic breast cancer patients, we really recommend that they’ve had genetic testing to look for DNA changes like BRCA mutations that will lead to treatment options. For metastatic triple-negative disease, it’s important to make sure that you’re providers are testing for PDL1, which would make you a candidate for immunotherapy. And then, the more we learn about clinical trials, the more we have options for patients that have had drug-based DNA or genome-based testing. So, that’s an important term for patients to become familiar with is genomic testing.

And I think when you bring that up with your providers, they’ll know what you’re talking about and they’ll know that what you’re potentially interested in is new targeted therapy for the cancer that may either come in combination with chemotherapy or as a standalone treatment option. If you don’t have those options that are available, and FDA approved basis for regular routine patient care, there is always the option of clinical trials.

And so, if that is something that you’re interested in, genomic testing will often open the way. So, I think as you’re writing notes when you’re talking to your providers, you might wanna jot down whether or not you’ve had genetic testing and whether or not you’ve had genomic testing in the past, as both of those things will help potentially address all of your treatment options.

I’ve very hopeful about the research that is going to lead to new developments for breast cancer treatment in the next few years.

I think what we’ve seen both at this San Antonio Breast Cancer Symposium as well as other conferences in the recent past has been a lot of focus on finding the right treatment for the right patient at the right time. And so, patients seem to be very interested in finding out this information. They often come to clinic armed with the most recent data, which allows their providers to have really informed discussions about what the best treatment might be. And to talk about if the new treatments are not great right now, what treatments might look like in the future.

I think the other thing that’s encouraging about the research that we’ve seen presented at this conference is that some of these trials are very, very large. For example, the RxPONDER trial was a trial of over 9,000 patients. And I really think that’s amazing to get that many patients interested in research that may not directly impact their patient care but will impact the care of others moving forward.

It’s just a sign that our breast cancer patients are empowered, and they want to make a difference in the scientific community as a whole.

 

How Can You Advocate for the Best Breast Cancer Care?

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How Can You Advocate for the Best Breast Cancer Care? from Patient Empowerment Network on Vimeo.

Breast cancer expert Dr. Julie Gralow explains how you can advocate for the best metastatic breast cancer care, through speaking up, utilizing care team members and taking key steps to achieving better care.

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:                  

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 going to 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.

Metastatic Breast Cancer Treatment and Research News

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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

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What Do Breast Cancer Patients Need to Know About COVID?

Essential Testing Following a Metastatic Breast Cancer Diagnosis

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

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?

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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

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Are You Prepared for Your Breast Cancer Appointment?

Essential Testing Following a Metastatic Breast Cancer Diagnosis

What Do Breast Cancer Patients Need to Know About COVID?
 

Transcript:

Dr. Flaum:                  

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

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

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

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

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

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

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

Essential Testing Following A Metastatic Breast Cancer Diagnosis

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

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

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

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Transcript:

Dr. Flaum:                  

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

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

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

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

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

What Could Advances in Breast Cancer Research Mean for You?

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

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

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

See More From INSIST! Metastatic Breast Cancer

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

What Are Essential Genetic Tests for Metastatic Breast Cancer Patients?

Metastatic Breast Cancer: Debunking Common Misconceptions
 

Transcript:

Katherine:                  

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

Dr. Gralow:                

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

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

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

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

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

What Is the Role of Genetic Testing in Breast Cancer?

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

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

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

See More From INSIST! Metastatic Breast Cancer

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

What Are Essential Genetic Tests for Metastatic Breast Cancer Patients?

Metastatic Breast Cancer: Debunking Common Misconceptions
 

Transcript:

Katherine:                  

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

Dr. Gralow:                

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

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

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

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

Katherine:                  

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

Dr. Gralow:                

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

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

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

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

Katherine:                  

How is testing administered?

Dr. Gralow:                

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

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

Factors That Guide a Metastatic Breast Cancer Treatment Decision

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

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

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

See More From INSIST! Metastatic Breast Cancer

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

What Are Essential Genetic Tests for Metastatic Breast Cancer Patients?

Metastatic Breast Cancer: Debunking Common Misconceptions
 

Transcript:

Katherine:                  

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

Dr. Gralow:                

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

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

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

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

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

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

Katherine:                  

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

Dr. Gralow:                

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

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

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

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

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

How Genetic Mutations Affect Metastatic Breast Cancer Prognosis and Treatment

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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?

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

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

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

See More From INSIST! Metastatic Breast Cancer

Related Resources:

 

How Genetic Mutations Affect Metastatic Breast Cancer Disease Progression and Prognosis

Factors That Guide a Metastatic Breast Cancer Treatment Decision

How Can You Advocate for the Best Breast Cancer Care?
 

Transcript:

Katherine:                  

What advances have there been in testing?

Dr. Gralow:                

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

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

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

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

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

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

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

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

Katherine:                  

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

Dr. Gralow:                

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

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

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