Tag Archive for: medical oncologist

What Could Advances in Lung Cancer Research and Treatment Mean for You?

What Could Advances in Lung Cancer Research and Treatment Mean for You? from Patient Empowerment Network on Vimeo.

Lung cancer expert Dr. Manish Patel discusses how lung cancer treatment approaches have evolved, specifically around targeted therapy and immunotherapy. Dr. Patel also provides advice for learning about and participating in clinical trials.

Dr. Manish Patel is a medical oncologist and Associate Professor of Medicine in the Division of Hematology, Oncology and Transplantation at the University of Minnesota. Learn more about Dr. Patel, here.

See More From Engage Lung Cancer

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Shared-Decision Making Your Role in Lung Cancer Treatment Choices

Why Should You Ask About Lung Cancer Biomarker Testing


Transcript:

 Katherine Banwell:

When it comes to lung cancer research and emerging treatment options, what are you excited about, specifically?

Dr. Patel:

Well, I’m really excited about the fact that in 2021 chemotherapy is really no longer the backbone of treatment. It’s really now become where we are really focusing on whether immunotherapy is the main modality of treatment or if it’s a targeted therapy.

And while we do still have chemotherapy and we use it, it’s not the main focus of our treatment. So, that’s really exciting. I personally am extremely excited about all of the advances in immunotherapy and the new methods that are coming across in new clinical trials to improve upon immune responses in patients with lung cancer.

Katherine Banwell:

When do you think a clinical trial should be considered for lung cancer treatment?

Dr. Patel:

Well, I think that’s a great question. And I think, honestly, it could be considered at any point in the patient’s treatment plan. Now, just to expound on that a little bit further, I think in the setting where a patient should be cured of their lung cancer with the treatment that we propose, we have to be careful that we are putting in adequate safeguards that the trial that we propose ensures that they’re receiving standard of care treatment but maybe something additional to try to improve upon that treatment.

On the other hand, if a patient has a more advanced cancer, then there is little bit more leeway in terms of the things that we can try to do. But of course, we always want to make sure that whatever we offer them, we have a reasonable expectation of working as well or better than the standard of care.

Katherine Banwell:

How can patients stay up to date on research?

Dr. Patel:

I think there are a couple of very useful resources online to stay abreast of things. A particular website that I think is very useful for patients is something called YouAndLungCancer.com.

And that is a fairly expansive portal that is patient-focused and really provides a lot of video tutorials on lung cancer, different treatments at different stages, new treatments that are available. And that’s a site that gets updated fairly regularly in terms of standard of care. And so, as we are in a phase where lung cancer research is really advancing very quickly, and these updates are important that they’re, you know, sort of sharing all of the new things that are coming along in lung cancer. 

Why Should You Ask About Lung Cancer Biomarker Testing?

Why Should You Ask About Lung Cancer Biomarker Testing? from Patient Empowerment Network on Vimeo.

Biomarker testing is a vital component of lung cancer care. Dr. Manish Patel, a lung cancer expert, shares important questions for patients to ask about this essential testing to help ensure optimal care.

Dr. Manish Patel is a medical oncologist and Associate Professor of Medicine in the Division of Hematology, Oncology and Transplantation at the University of Minnesota. Learn more about Dr. Patel, here.

See More From Engage Lung Cancer

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Shared-Decision Making Your Role in Lung Cancer Treatment Choices


Transcript:

 Katherine Banwell:

Why should lung cancer patients ask their doctor about biomarker testing?

Dr. Patel:

It’s extremely important. Biomarker testing is really the guiding principles by which we make a treatment plan for lung cancer patients in 2021.

We know that every patient’s lung cancer is a little bit different at the molecular level. So, they might look the same under the microscope, but, you know, if we get to a more deeper level, we can understand that they are quite different and they may respond differently to different treatments.

And so, it’s extremely important. And I think it’s important to know that nationwide we don’t always do a great job of doing real adequate biomarker testing. And so, from a patient perspective, it’s really useful to be an advocate for yourself and to ask your physician, you know, “Have we done biomarker testing, and to what extent have we done biomarker testing?” because it’s not uniform across the country at the moment.

Katherine Banwell:

Are there specific biomarkers that affect treatment choices?

Dr. Patel:

Absolutely there are. So, as an example, the molecular testing with DNA mutation analysis – so we actually look at the mutations that are present within a patient’s tumor, and that really does define a group of patients both in the curative setting and in the setting with more advanced disease that defines our treatment choices. Likewise, PD-L1 is a biomarker now that is being incorporated onto whether or not we use immunotherapy or whether we use immunotherapy with chemotherapy for patients that don’t have mutations.

So, it’s become an extremely important part of our treatment regimen. 

Shared Decision-Making: Your Role in Lung Cancer Treatment Choices

Shared-Decision Making: Your Role in Lung Cancer Treatment Choices from Patient Empowerment Network on Vimeo.

Lung cancer treatment decisions involve various factors, but what role should the patient play when choosing therapy? Lung cancer expert Dr. Manish Patel explains the considerations involved, the concept of shared decision-making when making a treatment choice, and provides questions to ask about a proposed treatment plan.

Dr. Manish Patel is a medical oncologist and Associate Professor of Medicine in the Division of Hematology, Oncology and Transplantation at the University of Minnesota. Learn more about Dr. Patel, here.

See More From Engage Lung Cancer

Related Resources:

Expert Perspective Exciting Advances in Lung Cancer Treatment and Research

Why Should You Ask About Lung Cancer Biomarker Testing?

Why Should You Ask About Lung Cancer Biomarker Testing?


Transcript:

Katherine Banwell:

When making a treatment choice, what three key considerations are there for lung cancer patients?

Dr. Patel:

Well, I think always the first one that’s most important is really the patient in front of me, you know, what their physical function is, what their other medical problems that they might have. Number two is always going to be to consider the stage of the cancer, how advanced the cancer is. And then really with regards to lung cancer these days, we really have to consider what kind of lung cancer it is. And I don’t mean necessarily just differentiating between the kinda major subtypes of lung cancer, but really looking at more detailed understanding of the specific type of lung cancer because it does, sort of, guide our treatment.

Katherine Banwell:

The term “shared decision-making” is being used a lot lately when talking about patient care. What does that term mean to you?

Dr. Patel:

Well, I think what that means is as the oncologist – the treating oncologist – my role is to educate the patient on what the treatment options are, give my recommendations of what I think the best options are for that individual patient.

But really the shared decision-making ultimately means that we have a discussion about what the goals of the patient are and how those match up with what my recommendations are and then come up with a treatment plan that suits both mine and the patient’s needs.

Katherine Banwell:

I know some patients are hesitant to talk to their doctor about questions they may have about how they’re feeling.

Does that come into the shared decision process?

Dr. Patel:

I think it does in some ways. I mean, we do try to explore how much the patient is understanding from what we’re talking about, also make a lot of attempts to understand the concerns or hesitations that a patient might have about what we’re talking about, or perhaps if they are hesitant to talk about certain aspects of their health with us. But we do try to tease that out as much as we can in our patient encounters so we can make really the best decision for that patient.

Katherine Banwell:

Are there questions that patients should consider asking about their proposed treatment plan?

Dr. Patel:

Well, I think it’s always useful for patients to ask, “What can they expect?” You know, we talk a lot about potential side effects – what can happen with the treatments – and oftentimes we’re discussing them in sort of worst-case scenarios.

But I think in some ways it’s sometimes helpful for patients to know what do we expect to happen, why we are discussing the extreme cases – best- and worst-case scenarios – really having an idea of what they should expect from treatment. 

How to Locate Prostate Cancer Clinical Trials and Improve Awareness

How to Locate Prostate Cancer Clinical Trials and Improve Awareness from Patient Empowerment Network on Vimeo.

 How is prostate cancer impact different for some populations? Watch as experts Dr. Yaw Nyame and Sherea Cary share the benefits of clinical trials, reliable clinical trial resources, and how clinical trial participation rates can be improved for better care.

See More From Best Prostate Cancer Care No Matter Where You Live


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Transcript:

Sherea Cary: 

What advice do you have for prostate cancer patients about locating a clinical trial? Where can you find one? 

Dr. Nyame: 

Clinical trials tend to happen at the big cancer centers and the big academic university centers, although many of those programs will have affiliate partners out in the community. The easiest way to learn about clinical trials is to start by asking the physician that’s treating you for your prostate cancer, oftentimes, they’ll have resources and connections to the trials directly or are the people who are administering them. However, other great sources are going to be patient advocacy networks, and there are many of them for prostate cancer, there’s one…there are several. I’ll start naming a few. They have the Prostate Cancer Foundation, you have Us TOO, you have Zero Cancer, you have a PHEN, Prostate Health Education Network, which is an advocacy group for Black men with prostate cancer. So, these are all great sources of finding out what clinical trials exist, and in addition, you can just get on the Internet and Google if that’s something you have access to. The trick is navigating all the information, and I think knowing what trials are available for you, whether you qualify, that kind of thing can be difficult, and that’s ultimately where finding a provider, whether it’s your direct urologists or radiation oncologist or whoever is helping treat your prostate cancer, either them directly or sometimes seeking a second opinion, and going to a place where you might find someone who has some expertise in trials, if that’s something that you’re interested in. 

Sherea Cary: 

My father participated in a clinical trial, it was going on, I think the time of his treatment, and it was offered to us, and he was at a big facility here in Houston that offered…ask him if he wanted to participate. We did a lot of research. We said we’d try it. And we were glad to be able to participate. I participated in clinical trials also for different health conditions, because I believe it’s important that we have to participate in order for our people to gather the information that’s necessary. So, thank you for that. 

Dr. Nyame: 

Absolutely, you know I think there are a lot of reasons that we think that our Black community, for instance, may not participate in a clinical trial given the history of medical experimentation and various forms of abuse that have existed in our history. But what I recently heard from our partner of our community partners at PHEN, when they surveyed Black men about prostate cancer clinical trials, was that although there was some concern about trust in the history, that the overwhelming majority of the men wanted to participate, but they never were asked. And that’s really stuck with me, and I think that Black men are under-represented in clinical trials, and we have to find ways to be more inclusive and understand what barriers might exist into participation so that we can have that data to care better for the population. 

Why Is Prostate Cancer Often Referred to As a Couples’ Disease?

Why Is Prostate Cancer Often Referred to As a Couples’ Disease? from Patient Empowerment Network on Vimeo.

Prostate cancer is often referred to as a disease of couples, but why is that? Watch as expert Dr. Yaw Nyame shares the impact of social support on prostate cancer outcomes and ways that family and friends can help with prostate cancer care.

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Transcript:

Sherea Cary: 

So, some people may consider prostate cancer a couples’ disease. What advice would you give to a care partner? My father was a prostate cancer survivor, my mother was very supportive of him, but I took much of the lead as far as being his caregiver and coordinating things between my father, his doctors’ appointments, and with my siblings. 

Do you believe that support people, caregivers, such as children, are able to also assist in receiving care? 

Dr. Nyame: 

Absolutely. The data is overwhelming in this scenario, patients who are partnered or have strong social support do better, and I always say that the patients who have the best outcomes when it comes to cancer, have someone like you, Sherea in their life. It’s not surprising, given the burden of cancer treatment, that having someone that can help navigate all the aspects of your care and be there to support you leads to better outcomes and better satisfaction with the treatments that you choose. A cancer diagnosis, especially prostate cancer diagnosis, a disease that has a very high cure rate, has a very long-life span, but has really life-altering potential consequences of the treatments you received, has an impact on what we return for survivorship. So how do you live with your cancer, and so the individuals that are there to support you through that journey are absolutely critical.  

How Can a Multi-Disciplinary Team Benefit Prostate Cancer Patients?

How Can a Multi-Disciplinary Team Benefit Prostate Cancer Patients? from Patient Empowerment Network on Vimeo.

 A prostate cancer multi-disciplinary team can benefit patient care. Watch as expert Dr. Yaw Nyameexplains the typical steps taken through prostate cancer care and how the team members can vary for localized prostate cancer versus advanced prostate cancer. 

See More From Best Prostate Cancer Care No Matter Where You Live


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How Has the Onset of Prostate Cancer Evolved?


Transcript:

Sherea Cary: 

What does a multi-discipline approach to prostate cancer look like?  

Dr. Nyame: 

Well, when you think about prostate cancer and how it’s diagnosed and how it’s treated, you’re talking about a process that involves a team, the process often starts with your primary care physician, he or she may order a PSA test, which will prompt a biopsy if it’s positive. So that’s the step one is that relationship you have with your primary care physician. Step two is going to be your urologist, that’s the person that’s going to do your biopsy, and if you are diagnosed with prostate cancer that person in conjunction with your primary care physician is then going to be leading this process of do we actively watch your cancer because it’s a low risk, or do we seek treatment because it’s localized, meaning it’s in the prostate and we can still get your treatment with curative intent as we call it, or has it spread? And in that case, your options for a doctor are different on the watch side, you’re probably looking at a urologist who’s watching closely, on the localized side, you’re going to talk to maybe a radiation specialist or a urologist, because both treatments are equal and their effectiveness from cancer treatment.  

But they have different side effects. And I think to get good information about what treatment is best for you, you should see both, and then on the advanced side, you’re talking about a medical oncologist that’s going to help navigate all of the various treatments that we have now for stage IV prostate cancer, and even in that setting, you might still find yourself considering a clinical trial with someone like a urologist or getting radiation treatment, which can be standard of care in select patients that have stage IV cancer. So, as you can see, it is a very wide range of individuals that are helping take care of your cancer, and that’s just on the treatment side, that’s not talking about any of the other supportive services that you may need that may exist either in your community or in your health systems where you’re getting treated. And those can include patient navigators, social workers, the various nursing services, nutritionists, there are a lot of people that you may want to put on your team as you’re considering your care.  

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

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?

How Can You Advocate for the Best Breast Cancer Care?

Factors That Guide a Metastatic Breast Cancer Treatment Decision

 


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.

 

Breast Cancer Research News: SABCS Conference Highlights

Breast Cancer Research News: SABCS Conference Highlights from Patient Empowerment Network on Vimeo

Expert Dr. Megan Kruse shares highlights from the 2020 San Antonio Breast Cancer Symposium (SABCS). Dr. Kruse provides an overview of what this news means for early stage breast cancer patients, along with her optimism about the future of breast cancer research and treatment.

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

See More From The Pro-Active Breast Cancer Patient Toolkit

Related Resources:

 

Transcript:

Dr. Kruse:                   

The San Antonio Breast Cancer Symposium is a national meeting with international presence that combines all of the latest data from research on breast cancer topics. It involves clinical research, basic science research, a lot of patient, and patient advocate support.

And the idea here is to bring together all the different disciplines that are involved in breast cancer patient care and do the best information and knowledge sharing that we can each year.

This year’s San Antonio Breast Cancer Symposium brought us a lot of interesting research focusing on early-stage breast cancer patients. I think the most important presentations that were given had to do with the treatment of high-risk lymph node-positive hormone receptor-positive breast cancer patients. And these were really across three abstracts. The first abstract of interest was the Monarch E study, which looked at high-risk women with hormone receptor-positive HER2-negative breast cancer and optimizing their medical therapy.

So, these patients are typically treated with anti-estrogen therapy and the idea of the research that was presented was if the addition of a targeted medication called abemaciclib or Verzenio could help to improve outcomes for women in this population. And what the trial found was that for women who took their anti-estrogen therapy for the usual length of time but added the abemaciclib for the first two years of that anti-estrogen therapy that there is actually an improvement in cancer-free survival time or an improvement in cure rates. And this was important because these women may not benefit from chemotherapy, as we’ll talk about in another abstract.

An addition research presentation that was given that goes alongside of the monarch E study was that of the Penelope B study. And the Penelope B took a similar population to what was studied in Monarch E. So, again high-risk women with lymph node-positive, hormone receptor-positive, HER2-negative breast cancer; however, in Penelope B, all of these patients had received pre-surgery chemotherapy.

And in order to qualify for the trial, the patients had to have some cancer that remained in the breast or the lymph nodes that was taken out at the time of their surgery. So, these are patients clearly in which chemotherapy did not do the whole job in terms of getting rid of the cancer. And again, the idea here was to add a second targeted therapy to the endocrine therapy to see if that would improve cancer-free time for patients in this population. The difference in this study was that the partner targeted therapy that was used was a drug called palbociclib or Ibrance.

And the drug was actually only used for one year in combination with endocrine therapy rather than two years as was used in the Monarch E study with abemaciclib. Interestingly enough, the Penelope B study was a negative study, meaning that it did not improve the cancer-free survival time for women who took the endocrine therapy plus targeted therapy compared to women who took the endocrine therapy alone.

So, I think that these are two interesting studies that one should look at together. And clearly, may impact what we do for the treatment of high-risk hormone receptor-positive women moving forward. The third abstract that I’d like to touch on that I think was important for women with early-stage breast cancer is the RxPONDER study, also known as SWOG 1007. And this study again was looking at lymph node-positive, hormone receptor-positive HER2-negative breast cancer patients and seeing if the addition of chemotherapy helped to improve their cancer-free survival compared to anti-estrogen therapy alone.

And so, in this study, while the study population was all women with early-stage breast cancer, meeting the one to three lymph node-positive criteria, you really have to break the results down into the results for pre-menopausal women and the results for post-menopausal women.

Because overall the study really showed no significant benefit to chemotherapy on top of endocrine therapy for women in this population; however, we did see that there was a clear benefit for women who were pre-menopausal. So, the women who had no benefit from chemotherapy were largely those who were post-menopausal, while those who were pre-menopausal derived extra benefit from chemo on top of anti-estrogen therapy. And that benefit depended on what the Oncotype recurrent score was.

With women that had the lowest of the recurrent scores having a chemo benefit of about three percent going up to over five percent for women who had Oncotype recurrent scores in the mid-teens to 25 range. In both of these groups, women who had Oncotype scores of 26 or above would have chemotherapy as per our standard of care.

So, I think that this abstract is important because in the past women who had lymph node-positive breast cancer generally received chemotherapy no matter what. More recently we’ve understood that not all of these cancers are created equal and that some cancers may not actually have benefit from chemotherapy in terms of improving cure rate. So, this study is a big step forward to help individualize and specify the treatment for women with lymph node-positive, hormone receptor-positive, HER2-negative early breast cancer.

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?

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

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.

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Transcript:

Dr. Flaum:                  

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

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

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

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

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

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

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

Essential Testing Following A Metastatic Breast Cancer Diagnosis

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

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

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

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Transcript:

Dr. Flaum:                  

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

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

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

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

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

What Could Advances in Breast Cancer Research Mean for You?

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

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

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

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

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Transcript:

Katherine:                  

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

Dr. Gralow:                

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

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

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

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

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

What Is the Role of Genetic Testing in Breast Cancer?

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

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

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

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

What Are Essential Genetic Tests for Metastatic Breast Cancer Patients?

Metastatic Breast Cancer: Debunking Common Misconceptions

 

Transcript:

Katherine:                  

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

Dr. Gralow:                

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

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

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

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

Katherine:                  

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

Dr. Gralow:                

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

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

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

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

Katherine:                  

How is testing administered?

Dr. Gralow:                

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

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

Factors That Guide a Metastatic Breast Cancer Treatment Decision

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

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

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

See More From INSIST! Metastatic Breast Cancer

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

What Are Essential Genetic Tests for Metastatic Breast Cancer Patients?

Metastatic Breast Cancer: Debunking Common Misconceptions

 

Transcript:

Katherine:                  

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

Dr. Gralow:                

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

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

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

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

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

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

Katherine:                  

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

Dr. Gralow:                

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

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

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

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

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