What Questions Should Metastatic Breast Cancer Patients Ask Before Starting a Treatment Plan?

What Questions Should Metastatic Breast Cancer Patients Ask Before Starting a Treatment Plan? from Patient Empowerment Network on Vimeo.

Before metastatic breast cancer treatment begins, it’s important to speak up and ask questions. Expert Dr. Sarah Sammons shares key questions patients should ask to ensure a personalized approach to their care and treatment.

Dr. Sarah Sammons is an oncologist at Duke Cancer Institute and Assistant Professor of Medicine at Duke University School of Medicine. Learn more about Dr. Sammons here.

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Which Metastatic Breast Cancer Treatment Is Right for You? Guide

An Overview of Metastatic Breast Cancer Treatment Options

Key Considerations When Making Metastatic Breast Cancer Treatment Decisions


Transcript:

Katherine:

What key questions do you think patients should ask about their proposed treatment plan, to make sure they’re getting the most personalized approach for their disease?

Dr. Sammons:

That’s a great question. So, first and foremost – when you get an initial diagnosis of metastatic breast cancer, it can be nearly debilitating mentally at first, so it’s a little bit hard to be an advocate for yourself.

But it is so important, eventually, to become an advocate for yourself and the first thing that I would say is it’s very important that you have had a biopsy of a metastatic site. So, if something shows up on a scan that looks abnormal – maybe a liver legion or a lung legion – it’s very important that that area is biopsied and checked again for estrogen, progesterone, and HER2. And the reason for that is – there’s a phenomenon called subtype switching. So, a patient can – maybe her early-stage breast cancer was estrogen receptor-positive. There’s a 15 to 20 percent chance that her metastatic disease could be estrogen-negative, and it’s critical that we know what the estrogen and the HER2 are, so that we can treat them with the initial best treatments.

So, that’s number one. I think it’s very important to have a biopsy of your metastatic site, to repeat that estrogen and HER2.

Next, pretty important to have had at least germline BRCA testing. And the reason for that is: We now have drugs, the PARP inhibitors that I talked about before, that specifically benefit patients that have a BRCA mutation.

And then, the next would be – is there a role for next generation sequencing, which is the somatic gene testing of the patient’s tumor.

I would say practice patterns differ. For HER2-positive breast cancer, it’s probably not important to have that upfront because we have a very – it’s critical that we know that you’re HER2-

positive, so that we can give you those best HER2 targeted therapies in the first few lines. But we’re really not going to use that genomic sequencing information for really the first couple of years in metastatic, HER2-positive breast cancer.

For hormone receptor-positive breast cancer, I do think it’s pretty important to know what your genomic testing is – your next generation sequencing is – upfront. If you have an ESR1 mutation, then we know that you’re resistant to certain types of endocrine therapy, and we would not give you them. If you have a PI3-Kinase, then we would give you that if you qualified, otherwise we would give you that drug that targeted the PI3-Kinase mutation probably in the second line.

So, next generation sequencing is pretty important, either in first or second line, in hormone receptor-positive breast cancer.

Triple-negative breast cancer – the most important thing upfront is to know what your PDL1 status is. And it’s very important that if you’re PDL1-positive, you get immunotherapy with your first treatment because we know that immunotherapy, if you get it in later lines of treatment, does not work as well as if you get it in the first line.

So, it’s always really tough for patients to wait a couple weeks to get started on treatment, but as long as your disease is not growing so rapidly that your physician is concerned, which is on the rare end, it’s good to get all your ducks in a row, get all of the information that you need, so that you can be started on the best treatment.

Katherine:

Dr. Sammons, why should patients feel like they should speak up and that they have a voice?

Dr. Sammons:

Patients should feel like they should speak up and have a voice because this is their life. This is your life. This is your treatment. This is – nobody is going to advocate for you as well as yourself. If you’re lucky, you’ll find a physician that is an advocate, and many of us are, but nobody will advocate for you as well as you will advocate for yourself. So, that’s reason number one.

And reason number two would be: we’re all humans. Your doctors are humans. Some physicians, especially physicians in the community, may not only treat breast cancer. They may treat every single type of cancer, and it’s very hard to stay specifically on top of all of the new drugs and new options coming out in every tumor type; it’s virtually impossible.

So, I just think it’s important to be an advocate. Never be afraid to ask a question. Most physicians should not feel threatened by that. We like a patient to be engaged. So, never worry or be fearful about that. 

An Expert Review of Emerging Metastatic Breast Cancer Research

An Expert Review of Emerging Metastatic Breast Cancer Research from Patient Empowerment Network on Vimeo.

What’s the latest in metastatic breast cancer (MBC) research? Expert Dr. Sarah Sammons shares an overview of emerging treatment options and how they could be utilized in MBC care.

Dr. Sarah Sammons is an oncologist at Duke Cancer Institute and Assistant Professor of Medicine at Duke University School of Medicine. Learn more about Dr. Sammons here.

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Why Should Metastatic Breast Cancer Patients Consider a Clinical Trial?


Transcript:

Katherine:

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

Dr. Sammons:

That’s a really good question. I think, right now, I’m very interested in a class of drugs called antibody drug conjugates.

What antibody drug conjugates are – they take a monoclonal antibody, which is – most patients have heard of Herceptin. So, Herceptin is an antibody which goes in and targets HER2. But that antibody is actually linked to a payload of chemotherapy cells. But instead of just – regular chemotherapy we inject that chemotherapy into the veins, it goes all throughout the body, it can be fairly toxic.

Antibody drug conjugates specifically find the cells that have that biomarker, like HER2, or TROP2, or HER3, and they find that cell, and they don’t release their chemotherapy until they’re taken up by that cell. So, it’s more a targeted, focused chemotherapy.

There is an antibody drug conjugate in HER2-positive breast cancer called Enhertu, or trastuzumab deruxtecan, which is – has been shown to have excellent efficacy in very heavily pre-treated HER2-postitive breast cancer.

It’s moving into earlier lines of therapy. The drug is so effective in HER2-positive breast cancer, we’re also looking at it in something called HER2-low breast cancer. So, breast cancers that we never thought before would respond to HER2 targeted therapy is – it appears that even if they express a little of HER2, this drug might have efficacy. So, that’s in clinical trials, and that’s really exciting.

What’s also great, is about 60 percent of women with hormone receptor-positive breast cancer are HER2-low. So, that could be a really great drug option in the future for those patients.

There’s another antibody drug conjugate called sacituzumab govitecan, which is approved in triple-negative breast cancer, and was shown to improve overall survival, which you always want at the end of the day – a drug that is well-tolerated and helps patients live longer.

That drug is approved in triple-negative breast cancer, but we’re now looking at it in hormone receptor-positive breast cancer.

There are also a variety of other antibody drug conjugates in clinical trials. One that’s looking at HER3, a few others that are looking at HER2, and also TROP2.

So, I’m definitely excited about antibody drug conjugates.

I’m also very excited about the field of immunotherapy in general. Immunotherapy has sort of lagged behind in breast cancer compared to some other tumor types like lung cancer and melanoma. But in triple-negative breast cancer, we finally have approval for two types of immunotherapy, but only if they have a certain biomarker.

Right now, immunotherapy only helps patients with metastatic triple-negative breast cancer if they express something called PDL1. So, we have FDA approval for two different immunotherapies for PDL1-positive triple-negative breast cancer. And there are many different strategies ongoing in clinical trials with different types of immunotherapy that try to harness the patient’s immune system to fight the cancer, instead of just giving regular chemotherapy. It’s really trying to help the patient’s immune response help fight the cancer. 

Is Your Metastatic Breast Cancer Treatment Effective?

Is Your Metastatic Breast Cancer Treatment Effective? from Patient Empowerment Network on Vimeo.

How can metastatic breast cancer treatment effectiveness be gauged? Dr. Jane Lowe Meisel shares important indicators, including symptom improvement, and discusses periodic testing that can help track a patient’s treatment results.

Jane Lowe Meisel, MD is an Associate Professor of Hematology and Medical Oncology at Winship Cancer Institute at Emory University. Learn more about Dr. Meisel here.

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Transcript:

Katherine:

We have another question we received earlier, this one from Eileen. She asks, “How will I know whether my treatment is working?”

Dr. Meisel:

That’s a really good question. So, I think for patients who have symptoms from their cancer, they often will know the drug is working because their symptoms improve. Say if you have lung metastases and you are short of breath and your shortness of breath gets better. That’s a really good sign that the treatment is working. I would say that often what we are doing, and it depends a little bit on the regimen and what the patient is getting and how often they’re coming in.

But we’re checking labs as well and sometimes there are lab abnormalities when a patient is diagnosed with metastatic cancer that can then improve over time. So, for example, if someone has a heavy burden of bone involvement with breast cancer, there’s a lab value called the alkaline phosphatases that will often be elevated. If that starts elevated and comes down, that’s a really good sign. And some of their liver function tests that we check and if a patient has liver metastases, we often will see those come down if a patient is responding.

There are also, what we call tumor markers that we can check in patients with metastatic breast cancer. Those would be proteins in the blood basically that can be made by the breast cancer in abundance. And those are called CA27-29 and CA15.3. Some doctors check both of them. Some will just check one depending on which one their laboratory at their institution is running. But typically, I will check those at diagnosis of metastatic disease. And then if it’s elevated, I know it’s a good marker to follow for my patient. And then I’ll follow that monthly or every three weeks, depending on when the patient is coming in to see me.

And if I see that marker start to go down, it’s not an absolute, but it can be a good early indicator of improvement with the treatment. And then I think it varies a little bit from practice to practice and based on patient preference. But often there will be scans done when a patient is initially diagnosed to determine the extent of the disease. So, usually a CT scan of the chest and the abdomen and the pelvis or a PET scan, which some of you may have heard of. Either one of those is good.

And that can be done about every 12 weeks usually in the beginning, to make sure a patient is responding and once you feel confident that they are, those can be done less frequently. So, I would say the scans and the lab work and then the patient’s overall condition are usually the way that we look to see, are we having a response or not. 

Why Should Metastatic Breast Cancer Patients Consider a Clinical Trial?

Why Should Metastatic Breast Cancer Patients Consider a Clinical Trial? from Patient Empowerment Network on Vimeo.

Why should metastatic breast cancer patients consider participating in a clinical trial? Dr. Jane Lowe Meisel discusses when clinical trials may be considered, explains the stages of trials, and shares a valuable resource for patients.

Jane Lowe Meisel, MD is an Associate Professor of Hematology and Medical Oncology at Winship Cancer Institute at Emory University. Learn more about Dr. Meisel here.

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


Transcript:

Katherine:

So, you mentioned earlier, clinical trials. When should patients consider participating in a trial?

Dr. Meisel:

I think it’s a great question and I think the answer is really, almost any time. There are trials in every setting. So, I think one of the common misconceptions about clinical trials is that you really only should be in a clinical trial, or your doctor might only mention a clinical trial if they don’t have other options for you or if you’re really in stage. And I think that perception is changing. But I think the reality is that there are clinical trials in every setting.

So, we have clinical trails looking at prevention of breast cancer. Clinical trials looking to optimize early-stage treatment of breast cancer. Clinical trials looking at secondary prevention, so once you’ve had breast cancer, how can we reduce your risk of recurrence. And then lots of clinical trials in the metastatic setting both for patients who are initially diagnosed with metastatic breast cancer.

And then in second, third, fourth line and even for patients who have had tons and tons of additional therapy that we’re looking at new drugs for. So, I think at almost any juncture where you’re making a treatment change, it’s probably appropriate to say, would there be a clinical trail that you can think of that would be good for me in this setting? And it may be that there’s a one that’s 12 hours away, and it’s not convenient for you or feasible.

And maybe that your doctor doesn’t necessarily know of one but then that prompts them to ask a colleague who may be more involved in clinical trial design and development. Or it may be that there is one, but you ultimately choose not to pursue it because you have a different option. But I think it’s always appropriate to ask, would there be a trail for me? Because if there is, then maybe that opens up an option you hadn’t thought about before.

Katherine:

Sure. For patients who aren’t familiar with the stages of clinical trials, would you give us a brief overview of the stages?

Dr. Meisel:

Yeah. Absolutely. So, in terms of clinical trials that’re being done in humans, we talk about Phase I, Phase II, and Phase III typically. So, a Phase II clinical trial is typically an earlier stage trial.

Looking at either a drug that has not been tested in humans before or a drug that has not been tested in a particular combination in humans before. And so, those trials are done only in select institutions, usually academic institutions as opposed to private hospitals. And they often have what’s called a dose finding phase and then a dose escalation phase. So, the earliest part of those trials is actually looking at, what is the safest dose to give to patients?

So, they start the first patients at a low dose of the compound. And if those patients do well, the next patients that’re enrolled get enrolled at a slightly higher dose. And then up until they reach the highest dose they can find where people are tolerating it and doing reasonably well. And in those Phase I trials, doctors and investigators are also evaluating efficacy, is this drug working. But the primary goal of the early phase trial is actually to find the right dose to then study in larger groups. And so, if they find the right dose and there’s good biological rationale for the compound, then the trial would go on to a Phase II.

Which might be just what we call single arm Phase II study, where every patient is getting that experimental drug. And we monitor them to see, is the drug effective or is it less effective than the standard of care? Or sometimes they’re what we call, randomized Phase II trials where patients are randomized to either get the experimental drug, or to get what the standard of care would be in that situation. I think a lot of people get afraid about the idea of a randomized trial because they’re afraid they’re going to be randomized to a placebo. And that is really not done in the metastatic setting because it wouldn’t be ethical to give a patient with active cancer a placebo.

So, usually the randomization would be either to the study compound or to a standard of care drug. And then if things look good in a Phase II trial, then a Phase III study is done which is usually what the FDA requires to allow a drug to go on and be administered outside of a study for approval. And those Phase III trials tend to be larger studies that’re done in larger groups of patients with more statistical validity because of their size, to determine, is this drug really better than the standard. 

Key Considerations When Making Metastatic Breast Cancer Treatment Decisions

Key Considerations When Making Metastatic Breast Cancer Treatment Decisions from Patient Empowerment Network on Vimeo.

Making metastatic breast cancer treatment decisions involves weighing key factors. Dr. Jane Lowe Meisel shares important considerations that aid in choosing the best treatment for an individual patient.

Jane Lowe Meisel, MD is an Associate Professor of Hematology and Medical Oncology at Winship Cancer Institute at Emory University. Learn more about Dr. Meisel here.

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Transcript:

Katherine:

Yeah. Yeah. So, what factors are considered when deciding on the best treatment approach for an individual patient?

Dr. Meisel:

So, I think certainly the tumor type that we were talking about. Is it estrogen-positive or HER2-negative or HER2-positive?

I think response to past treatments, both in terms of if someone has had metastatic disease for a long time and has had a few treatments already, how long did they respond to those treatments and how completely did they respond to those treatments?

Did they have stable disease for a while, or did their cancer actively shrink?

And then I think other than that, it would be some of the things I touched on. Side effect profiles. Do patients have pre-existing neuropathy from other chemotherapy? If so, maybe you want to avoid a regimen that causes more neuropathy. Schedule. Some patients, it’s really important to be on a certain schedule, as opposed to a different schedule. I think whether there are clinical trials available instead of whatever the standard of care regimen would be is also important.

Because for some patients who are interested in pushing the envelope or who might be a great candidate for a particular trial, if there is one that they’re a candidate for that’s not horribly inconvenient from a logistics standpoint, then trials I think are also a great option to consider. So, I think from an effectiveness standpoint, you want to think about the tumor type response to past treatments. And then potentially, if the patient has had, what we call genomic profiling, where the tumor has been sent for basically genomic analysis, to see what genes might be mutated in the tumor that could potentially drive a response to a newer, different therapy.

All those things can be taken into account as we think about the cancer. But then there are the patient-specific factors, and I think those would be mainly side effects, schedule, clinical trials and desire or not to pursue those. And then, just what the patient’s perspective is on the plan that you’re offering them. 

An Overview of Metastatic Breast Cancer Treatment Options

An Overview of Metastatic Breast Cancer Treatment Options from Patient Empowerment Network on Vimeo.

What metastatic breast cancer (MBC) treatment options are available? Dr. Jane Lowe Meisel provides an overview of MBC treatment approaches, including CDK4-6 inhibitors, tyrosine kinase inhibitors, PARP inhibitors, and immunotherapy.

Jane Lowe Meisel, MD is an Associate Professor of Hematology and Medical Oncology at Winship Cancer Institute at Emory University. Learn more about Dr. Meisel here.

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Transcript:

Katherine:

Right.

Well, let’s talk about treatment options for advanced disease. Can you review the types of treatments available for metastatic breast cancer?

Dr. Meisel:

Absolutely. And what I’ll do is, I’ll give you a broad overview and then because there’s so much and this is such a rich environment, I mean, I give hour long lectures just about the treatment of metastatic triple-negative breast cancer to our fellows. So, there is so much meaty information here. But I’ll give an overview with some key buzzwords so then people can go look up things that matter more to them or interest them more. So, as I said, we start with thinking about, is this hormone receptor-positive or estrogen-positive breast cancer? Is this HER2-positive or is this triple-negative? And those factors really send us down different paths.

So, if someone is estrogen-positive, I had mentioned before the PALOMA and MONALEESA studies showing that CDK4-6 inhibitors, which is a class of drugs that the first one was approved in 2015 and then two others have been approved subsequently. So, relatively new drugs. But those drugs, which are pills, added to traditional anti-estrogen therapy which would be aromatase inhibitors or fulvestrant.

Are often great first line options for these patients. And people can do well for years on just that alone, with estrogen-positive metastatic breast cancer. On average, about two years before people progress and need something new. And then after that, there are lots of trials ongoing looking at different ways in which an estrogen-positive breast cancer might progress on that regimen and how do we target that. So that there are multiple other anti-estrogen options down the line that people can use in estrogen-positive breast cancer before they need to even think about going on to something like chemotherapy.

So, really lots and lots of options for those patients, but probably starting with a CDK4-6 inhibitor plus anti-estrogen combination. And then in HER2-positive breast cancer, typically the first line treatment would be what we call monoclonal antibodies directed at HER2. So, something like Herceptin and Perjeta, which you may have heard of. And often combined with chemotherapy. But again, this is one of those areas that is also very, I think the art of medicine is very important and patient dependent.

Some of these regimen depend a little bit on patient’s age and other medical problems and desires, whether to include chemotherapy along with that frontline anti-HER2 regimen. Or whether to think about something like anti-estrogen therapy if the patient is HER2-positive and estrogen-positive. And then there are a lot of other different things we’re also using in HER2-positive disease after patients progress on that initial therapy, so there are what we call, antibody drug conjugates, where a chemotherapy like drug is attached to an antibody that then brings the chemo to the HER2-positive cell and allows for chemotherapy penetration more directly.

And then a class of drugs called tyrosine kinase inhibitors, which are oral drugs that get directed at HER2. So, another really exciting area to treat and a place where we’ve seen so many advances. And then in triple-negative breast cancer, I’d mentioned that chemotherapy has really been the mainstay of treatment historically because there weren’t great targets. But recently we’ve seen that immunotherapy, along with chemotherapy drugs like Keytruda, which you may have heard of.

Or atezolizumab, which is Mesenteric, can be used along with chemo and patients that overexpress a molecule called, PDL1. And that can actually include not just how long patients spend on the first treatment, but how long they live. So, we’re seeing a lot of triple-negative patients being great candidates for immune-based regimens now. And then for patients who have inherited a BRCA gene mutation, which many of you may have heard of. That gene mutation can actually predispose a triple-negative patient to be more receptive to a class of drugs called PARP inhibitors.

So, drugs like Olaparib or Talazoparib are new drugs that’ve been approved in the last couple of years in triple-negative metastatic breast cancer for patients who carry a BRCA1 mutation or BRCA2 mutation. And then there are also antibody drug conjugates in triple-negative breast cancer as well. The Trodelvy that’s been approved and then of course others that are in clinical trials currently. So, as you can see, it’s complex. I mean, the treatment of metastatic breast cancer is complicated. And so, it’s important I think to really be able to have a dialogue with your provider about what they’re recommending for you and why.

And I think there are often lots of options. And so, as much as you can make your doctor aware of what matters to you in terms of what side effects are you most afraid of or would you like most to avoid, what dosing schedules would be idea for your schedule for the rest of your life. So that you can deal with taking kids to school or the job that you’re currently working on or whatever, I think helps your doctor help you come up with the right regimen for you.

What Metastatic Breast Cancer Patients Should Know About Treatment and Research

What Metastatic Breast Cancer Patients Should Know About Treatment and Research from Patient Empowerment Network on Vimeo.

What do metastatic breast cancer patients need to know about treatment and research? Dr. Jane Lowe Meisel shares updates and recommends resources for staying abreast of research news.

Jane Lowe Meisel, MD is an Associate Professor of Hematology and Medical Oncology at Winship Cancer Institute at Emory University. Learn more about Dr. Meisel here.

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Transcript:

Katherine:

So, let’s start by discussing the latest developments in treatment and research updates. Are there recent developments you feel breast cancer patients should know about?

Dr. Meisel:

Absolutely and I think it’s really been such a remarkable time because even during COVID, a pandemic, where I think a lot of people worried that research efforts would shut down or stall. We’ve still seen the approval of a number of drugs in the past year that’ve really already markedly changed lives. And a lot of important findings that’ve come out of other trials that they have opportunity to do that as well.

I think some of the biggest information that was presented at our most recent large meeting, which was the American Society of Clinical Oncology, or ASCO National Meeting in 2021, were a few things that pertain to the metastatic breast cancer population. One was two studies, the PALOMA-3 Trial and the MONALEESA-3 Trial, which looked at a class of drugs called CDK4-6 inhibitors along with anti-estrogen pills in metastatic estrogen-positive breast cancer.

And really confirm for patients that not only do these drugs improve the amount of time that people can stay on treatment before their cancer progresses, but actually improve how long people live. Even when they’re used very, very early on in treatment, they impact survival down the line for many, many years. So, it really confirms for physicians like me that this class of drugs should be used as the standard of care and first line for patients with estrogen-positive stage IV breast cancer, and I think that’s important for patients to know. Along those lines, there’s a drug called sacituzumab govitecan, or Trodelvy, which is a much easier to say name.

Katherine:

Yes.

Dr. Meisel:

A new antibody drug conjugate in triple-negative metastatic breast cancer. And we’ve also seen, since this drug was approved last year, it has markedly changed the lives of many patients with triple negative disease. And the study called the ascent trial, which is what led to that drug’s approval was studied further and some of these additional results presented at ASCO this year.

And found that this drug not only improves again, how long people get before they have to move on to another treatment, but actually improves how long people live as well, even when given later on in the course of therapy. So again, really encouraging use especially in triple-negative metastatic disease, which is hard to treat. And I think another study that’s really worth patients and doctors taking a hard look at, was actually a study that looked at patient outcomes and patient experience. This is a study that actually talked with metastatic patients and gathered their views on treatment related adverse effects.

Talked to patients about what adverse effects they were experiencing from drugs. How they managed those adverse effects. And found that most patients, over 90 percent, will be willing to talk about reducing the dose of drugs or changing dosing schedules, in order to improve quality of life. And I think that’s really important because a lot of times, the doses of drugs that get approved are the doses that are the highest doses that don’t cause extreme toxicity. But sometimes people can have effective, really good outcomes on lower doses and have much better quality of life.

And in metastatic breast cancer where really the goal often times is to help people live as long as they can, but also as importantly, as well as they can, be able to have those open-ended conversations between patients and doctors about what’s really impacting your quality of life now and how can we make that better is important. And this study I think really highlighted that both for patients and physicians, how important that back and forth is to having a successful outcome. Both in terms of how life is lived, but in terms of quality of that life.

Katherine:

Right. Right. How can patients stay up to date on developing research?

Dr. Meisel:

It’s so interesting because there is so much coming out and I think it can be hard to figure out what Phase I study that looks exciting is really going to become something, versus what really could be important in my treatment today. And what I always tell people is actually, the NCI website. So, the national cancer institute, has a phenomenal page looking at advances in breast cancer research. So, if you Google NCI advances in breast cancer research, there’s a great page that comes up. And it’s impressively up to date and I think very patient friendly.

Breaks things down into early stage and metastatic and then in the metastatic section, talks about estrogen-positive, HER2-positive, triple-negative, which we can talk about more today but are the three big subtype of metastatic disease that dictate how we treat them. And then have links to all the different research updates and talk about what these drugs are, what the classes are and what the settings are in which they’re studies.

And so, I think that’s a really great first stop and then the links can take you to all different stuff that’s on the page that you might want to look into more in depth. And then also, the Breast Cancer Research Foundation, which is a phenomenal organization. They have a great website, too and if you click around on the website, you can see not only who they’ve donated money to that’s doing promising research, they also have podcasts, they have a blog with science and research news. I think that’s a really great site for patients to use to stay updated. 

Which Metastatic Breast Cancer Treatment Is Right for You? Guide

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Which Metastatic Breast Cancer Treatment Is Right for You? What You Need to Know

Which Metastatic Breast Cancer Treatment Is Right for You? What You Need to Know from Patient Empowerment Network on Vimeo.

What do you need to know before deciding which treatment is best for YOUR metastatic breast cancer? Expert Dr. Jane Meisel reviews recent research news, discusses the role of key tests–including biomarker testing –in determining a treatment plan, and shares advice for self-advocacy.

Jane Lowe Meisel, MD is an Associate Professor of Hematology and Medical Oncology at Winship Cancer Institute at Emory University. Learn more about Dr. Meisel, here.

[Editor’s Note: On August 23, 2021, the U.S. Food and Drug Administration (FDA) approved the Pfizer-BioNTech COVID-19 Vaccine for individuals 16 years of age and older.]

Download Program Guide

See More From INSIST! Metastatic Breast Cancer

Related Resources:

 

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:

Katherine:

Hello and welcome. I’m Katherine Banwell, your host for today’s program. In today’s webinar, we’ll discuss how you can access the most personalized metastatic breast cancer therapy for your individual disease and why it’s vital to insist on key testing. Before we meet our guest, let’s review a few more important details. The reminder email you received about this program contains a link to program materials.

If you haven’t already, click that link to access information to follow along during the webinar. At the end of this program, you’ll receive a link to a program survey. Please take a moment to provide feedback about your experience today, in order to help plan future webinars. And finally, before we get into the discussion, please remember, this program is not a substitute for seeking medical advice. Please refer to your healthcare team – Please refer to your healthcare team about what might be best for you.

All right, let’s meet our guest today. Joining us is Dr. Jane Meisel. Dr. Meisel, welcome. Would you please introduce yourself?

Dr. Meisel:

Absolutely and thank you so much for having me. My name is Jane Meisel and I’m a medical oncologist at the Winship Cancer Institute at Emory University. I’ve been here for about six years and before that, I did my training in Boston and at Memorial Sloan-Kettering in New York. And I specialize in breast cancer and have had a lot of great opportunities to treat amazing patients and participate in a lot of research.

And I’m looking forward to having this discussion with you today.

Katherine:

Thank you for joining us, we really appreciate it. So, let’s start by discussing the latest developments in treatment and research updates. Are there recent developments you feel breast cancer patients should know about?

Dr. Meisel:

Absolutely and I think it’s really been such a remarkable time because even during COVID, a pandemic, where I think a lot of people worried that research efforts would shut down or stall. We’ve still seen the approval of a number of drugs in the past year that’ve really already markedly changed lives. And a lot of important findings that’ve come out of other trials that they have opportunity to do that as well.

I think some of the biggest information that was presented at our most recent large meeting, which was the American Society of Clinical Oncology, or ASCO National Meeting in 2021, were a few things that pertain to the metastatic breast cancer population. One was two studies, the PALOMA-3 Trial and the MONALEESA-3 Trial, which looked at a class of drugs called CDK4-6 inhibitors along with anti-estrogen pills in metastatic estrogen-positive breast cancer.

And really confirm for patients that not only do these drugs improve the amount of time that people can stay on treatment before their cancer progresses, but actually improve how long people live. Even when they’re used very, very early on in treatment, they impact survival down the line for many, many years. So, it really confirms for physicians like me that this class of drugs should be used as the standard of care and first line for patients with estrogen-positive stage IV breast cancer, and I think that’s important for patients to know. Along those lines, there a drug called sacituzumab govitecan, or Trodelvy, which is a much easier to say name.

Katherine:

Yes.

Dr. Meisel:

A new antibody drug conjugate in triple-negative metastatic breast cancer. And we’ve also seen, since this drug was approved last year, it has markedly changed the lives of many patients with triple-negative disease. And the study called the ascent trial, which is what led to that drug’s approval was studied further and some of these additional results presented at ASCO this year.

And found that this drug not only improves again, how long people get before they have to move on to another treatment, but actually improves how long people live as well, even when given later on in the course of therapy. So again, really encouraging use especially in triple-negative metastatic disease, which is hard to treat. And I think another study that’s really worth patients and doctors taking a hard look at, was actually a study that looked at patient outcomes and patient experience. This is a study that actually talked with metastatic patients and gathered their views on treatment related adverse effects.

Talked to patients about what adverse effects they were experiencing from drugs. How they managed those adverse effects. And found that most patients, over 90%, will be willing to talk about reducing the dose of drugs or changing dosing schedules, in order to improve quality of life. And I think that’s really important because a lot of times, the doses of drugs that get approved are the doses that are the highest doses that don’t cause extreme toxicity. But sometimes people can have effective, really good outcomes on lower doses and have much better quality of life.

And in metastatic breast cancer where really the goal often times is to help people live as long as they can, but also as importantly, as well as they can, be able to have those open-ended conversations between patients and doctors about what’s really impacting your quality of life now and how can we make that better is important. And this study I think really highlighted that both for patients and physicians, how important that back and forth is to having a successful outcome. Both in terms of how life is lived, but in terms of quality of that life.

Katherine:

Right. Right. How can patients stay up to date on developing research?

Dr. Meisel:

It’s so interesting because there is so much coming out and I think it can be hard to figure out what Phase I study that looks exciting is really going to become something, versus what really could be important in my treatment today. And what I always tell people is actually, the NCI website. So, the National Cancer Institute, has a phenomenal page looking at advances in breast cancer research. So, if you Google “NCI advances in breast cancer research,” there’s a great page that comes up. And it’s impressively up to date and I think very patient-friendly.

Breaks things down into early stage and metastatic and then in the metastatic section, talks about estrogen-positive, HER2-positive, triple-negative, which we can talk about more today but are the three big subtype of metastatic disease that dictate how we treat them. And then have links to all the different research updates and talk about what these drugs are, what the classes are and what the settings are in which they’re studied.

And so, I think that’s a really great first stop and then the links can take you to all different stuff that’s on the page that you might want to look into more in depth. And then also, the Breast Cancer Research Foundation, which is a phenomenal organization. They have a great website, too and if you click around on the website, you can see not only who they’ve donated money to that’s doing promising research, they also have podcasts, they have a blog with science and research news. I think that’s a really great site for patients to use to stay updated.

Katherine:

Let’s shift gears for a moment and talk about another time sensitive topic, COVID. Now that vaccines are available, are they safe and effective for breast cancer patients?

Dr. Meisel:

Yeah, I think the short answer to that is yes, absolutely. I’m encouraging all my patients, no matter what their treatment status is to go ahead and get vaccinated. And we are seeing now this third surge in COVID with cases rising all over the country, and really among unvaccinated populations. And with the delta variant being more transmissible, I think it’s all the more time, even if you haven’t considered vaccination up until now, to really go ahead and strongly consider getting a vaccine.

I think some of the hesitations that some of the people have talked to me about is that there were not a lot of active cancer patients, if any, included in the initial trials. And whereas that is true, it’s still the case that now, so many cancer patients have been vaccinated. We haven’t really heard about adverse effects in vaccination being something that’s higher in patients who have cancer who are on active treatment. I think the one challenge is, if you have a compromised immune system because of cancer treatment, there’s the possibility that you might not mount the same immune response to the vaccine as someone who doesn’t have cancer or isn’t getting active treatment.

So, while I would say yes, definitely get vaccinated, I would also at the same time encourage caution in saying, because you might not mount the same, 95 percent or whatever immune response, it may still be a good idea to wear a mask when you go to the grocery store, taking those precautions because no one really knows what’s coming and it’s better to be safe than sorry. But I think we will get a lot of information as the months go on about, do we need boosters? Who might need boosters more soon than others and some of that will get clarified for us, but my short answer would be yes, vaccines for all.

Katherine:

Excellent, that’s very helpful.

Dr. Meisel:

Thank you.

Katherine:

Since this webinar is focused on metastatic disease, would you define metastatic breast cancer for us?

Dr. Meisel:

Absolutely. And I think metastatic breast cancer is one of those terms that as doctors, we throw around a lot and often times don’t stop to check understanding as to what that means.

And what metastatic breast cancer is and means, is breast cancer that is spread outside of the breast and surrounding lymph nodes to another organ system. So, metastatic breast cancer, some of the most common places where it spreads are to the bone, to the skin, to the lungs, to the liver, to the brain. There are other places it can spread to. I’ve seen it on the ovaries, in the GI tract. But basically, when breast cancer spreads outside of the breast and surrounding lymph nodes to another organ system, that’s when we consider it metastatic.

Katherine:

How can a patient ensure they are getting an accurate diagnosis?

Dr. Meisel:

Another good question. And I think the most important thing when you’re considering whether or not you have a diagnosis of metastatic breast cancer is to get a biopsy of that metastatic site. So, you wouldn’t want to assume, just based on a CT scan that shows something in the bone that you have metastatic disease. Ideally, we would biopsy that spot or some spot that was indicative of metastatic disease to actually prove that there is metastatic cancer in that distant site.

Because sometimes it’s nothing. Sometimes you get scans and a little bone abnormality, maybe a scar from a prior fall. And then also, sometimes if it is metastatic, sometimes the breast cancer, the hormone receptor status, for example, can change from the primary site to the metastatic site. And that might impact treatment. So, it’s important to both get a metastatic biopsy to confirm diagnosis. And also, to understand what the treatment plan might be. And I think also for patients, just to make sure that you understand what your stage is, ask your doctor.

Say, what is my stage? Because sometimes doctors think people understand and they don’t actually, so checking that understanding is important. But if your doctor or provider is not actively checking your understanding, you can check it with them to make sure that if you are metastatic or have Stage IV disease, which is another way we define metastatic or talk about metastatic cancer, that you make sure you have the definition right.

Katherine:

Right, right. So, once someone has been diagnosed with metastatic disease, are there key tests that’re used to help understand how their disease may behave and progress?

Dr. Meisel:

Absolutely. So, I think the first thing as I said is that metastatic biopsy. Another thing that’s very important is understanding the hormone receptor status and the HER2 status of the breast cancer. And probably for a lot of you listening, if you have listened to metastatic breast cancer webinars before or maybe know someone or have had a diagnosis yourself, you’re well versed in this. But for some who may not be, I think a quick overview is maybe helpful. Breast cancer can be divided into three different subtypes. So, triple-negative, estrogen-positive or HER2-positive. And estrogen-positive breast cancer is the most common kind.

That tends to be driven by hormones and often treated with what we call, endocrine therapy. So, anti-estrogen pills, things like Tamoxifen or aromatase inhibitors are examples of that. And that’s one kind. And then there’s HER2-positive breast cancer, which is a type of breast cancer that over expresses a marker called HER2. And we now, since we know about that marker, have been able to develop a lot of different treatments that target HER2 selectively.

And can be used to treat that subtype. And then triple-negative is basically estrogen-negative, progesterone-negative and HER2-negative. And that type of breast cancer traditionally was treated essentially only with chemotherapy. But now we’ve had some breakthroughs, which we’ll talk about I think later in this program talking about immunotherapy and more targeted therapy for that. But those subtypes help determine how we treat patients. And it also can sometimes predict behavior.

I would say one of the other things that helps us predict behavior of metastatic disease is, if a patient had early-stage disease before, how quickly they developed metastatic disease. So, for example, someone who develops estrogen-positive metastatic breast cancer 12 years out from their original diagnosis is statistically more likely to have a slower progressing course of disease than someone who develops triple-negative metastatic disease very soon after their initial treatment. So, I would say that’s the primary thing we look at in terms of determining treatment plan and then predicting overall course.

Katherine:

Right. Well, let’s talk about treatment options for advanced disease.

Can you review the types of treatments available for metastatic breast cancer?

Dr. Meisel:

Absolutely. And what I’ll do is, I’ll give you a broad overview and then because there’s so much and this is such a rich environment, I mean, I give hour long lectures just about the treatment of metastatic triple-negative breast cancer to our fellows. So, there is so much meaty information here. But I’ll give an overview with some key buzzwords so then people can go look up things that matter more to them or interest them more. So, as I said, we start with thinking about, is this hormone receptor-positive or estrogen-positive breast cancer? Is this HER2-positive or is this triple-negative? And those factors really send us down different paths.

So, if someone is estrogen-positive, I had mentioned before the PALOMA and MONALEESA studies showing that CDK4-6 inhibitors, which is a class of drugs that the first one was approved in 2015 and then two others have been approved subsequently. So, relatively new drugs. But those drugs, which are pills, added to traditional anti-estrogen therapy which would be aromatase inhibitors or fulvestrant.

Are often great first-line options for these patients. And people can do well for years on just that alone, with estrogen-positive metastatic breast cancer. On average, about two years before people progress and need something new. And then after that, there are lots of trials ongoing looking at different ways in which an estrogen-positive breast cancer might progress on that regiment and how do we target that. So that there are multiple other anti-estrogen options down the line that people can use in estrogen-positive breast cancer before they need to even think about going on to something like chemotherapy.

So, really lots and lots of options for those patients, but probably starting with a CDK4-6 inhibitor plus anti-estrogen combination. And then in HER2-positive breast cancer, typically the first-line treatment would be what we call monoclonal antibodies directed at HER2. So, something like Herceptin and Perjeta, which you may have heard of. And often combined with chemotherapy. But again, this is one of those areas that is also very, I think the art of medicine is very important and patient dependent.

Some of these regiments depend a little bit on patient’s age and other medical problems and desires, whether to include chemotherapy along with that frontline anti-HER2 regimen. Or whether to think about something like anti-estrogen therapy if the patient is HER2-positive and estrogen-positive. And then there are a lot of other different things we’re also using in HER2-positive disease after patients progress on that initial therapy, so there are what we call, antibody drug conjugates, where a chemotherapy like drug is attached to an antibody that then brings the chemo to the HER2-positive cell and allows for chemotherapy penetration more directly.

And then a class of drugs called tyrosine kinase inhibitors, which are oral drugs that get directed at HER2. So, another really exciting area to treat and a place where we’ve seen so many advances. And then in triple-negative breast cancer, I’d mentioned that chemotherapy has really been the mainstay of treatment historically because there weren’t great targets. But recently we’ve seen that immunotherapy, along with chemotherapy drugs like Keytruda, which you may have heard of.

Or atezolizumab, which is Mesenteric, can be used along with chemo and patients that overexpress a molecule called, PDL1. And that can actually include not just how long patients spend on the first treatment, but how long they live. So, we’re seeing a lot of triple-negative patients being great candidates for immune-based regimen now. And then for patients who have inherited a BRCA gene mutation, which many of you may have heard of. That gene mutation can actually predispose a triple-negative patient to be more receptive to a class of drugs called PARP inhibitors.

So, drugs like olaparib (Lynparza) or talazoparib (Talzenna) are new drugs that’ve been approved in the last couple of years in triple-negative metastatic breast cancer for patients who carry a BRCA1 mutation or BRCA2 mutation. And then there are also antibody drug conjugates in triple-negative breast cancer as well. The Trodelvy that’s been approved and then of course others that are in clinical trials currently. So, as you can see, it’s complex. I mean, the treatment of metastatic breast cancer is complicated. And so, it’s important I think to really be able to have a dialogue with your provider about what they’re recommending for you and why.

And I think there are often lots of options. And so, as much as you can make your doctor aware of what matters to you in terms of what side effects are you most afraid of or would you like most to avoid, what dosing schedules would be idea for your schedule for the rest of your life. So that you can deal with taking kids to school or the job that you’re currently working on or whatever, I think helps your doctor help you come up with the right regiment for you.

Katherine:

Yeah. Yeah. So, what factors are considered when deciding on the best treatment approach for an individual patient?

Dr. Meisel:

So, I think certainly the tumor type that we were talking about. Is it estrogen-positive or HER2-negative or HER2-positive? I think response to past treatments, both in terms of if someone has had metastatic disease for a long time and has had a few treatments already, how long did they respond to those treatments and how completely did they respond to those treatments. Did they have stable disease for a while or did their cancer actively shrink?

And then I think other than that, it would be some of the things I touched on. Side effect profiles. Do patients have pre-existing neuropathy from other chemotherapy? If so, maybe you want to avoid a regiment that causes more neuropathy. Schedule. Some patients, it’s really important to be on a certain schedule, as opposed to a different schedule. I think whether there are clinical trials available instead of whatever the standard of care regiment would be is also important.

Because for some patients who are interested in pushing the envelope or who might be a great candidate for a particular trial, if there is one that they’re a candidate for that’s not horribly inconvenient from a logistics standpoint, then trials I think are also a great option to consider. So, I think from an effectiveness standpoint, you want to think about the tumor type response to past treatments. And then potentially, if the patient has had, what we call genomic profiling, where the tumor has been sent for basically genomic analysis, to see what genes might be mutated in the tumor that could potentially drive a response to a newer, different therapy.

All those things can be taken into account as we think about the cancer. But then there is the patient specific factors, and I think those would be mainly side effects, schedule, clinical trials and desire or not to pursue those. And then, just what the patient’s perspective is on the plan that you’re offering them.

Katherine:

What is biomarker testing and how do results impact treatment options?

Dr. Meisel:

Great question. So, I think people often confuse germline mutations and somatic mutations. So, I’ll talk about that a little bit as we talk ab out biomarkers. So, I think biomarkers in general are factors within the tumor that allow us to make treatment decisions. So, if a biomarker in the tumor can predict response to a certain type of treatment, we want to know what that biomarker is so we can better treat the patient and more elegantly design a regimen. So, for example, having an estrogen-positive tumor, estrogen positivity is a biomarker suggestive of response to anti-estrogen treatments, which is why we give anti-estrogen therapy to ER-positive breast cancers.

But more recently, we’ve been able to move a little bit beyond estrogen, HER2- and triple-negative as our subtypes and think a little bit more in some patients about more sophisticated biomarkers. And that’s where somatic mutation testing comes in. So, there are germline mutations, which are inherited mutations that’re present in every cell in your body. So, for example, if your mother was a BRCA mutation carrier and based that BRCA mutation down to you, you would have a germline BRCA mutation. So, your cancer would carry a BRCA mutation, but so would every other cell you have.

And that’s a biomarker. That would make you a candidate for something like a PARP inhibitor. But in cancers, which the genes in the cancer have gone awry by definition, there are often other biomarkers within that tumor that may make you a candidate for certain treatments. And so, those mutations that arise in the cancer itself are called, somatic mutations. Those are mutations in the tumor, can’t be passed down to your offspring or anything like that and were not inherited by your parents. But mutations that’ve accumulated over time as these cancer cells have gone awry.

And so, genomic testing, or biomarker testing can be done often on a metastatic specimen. So, to be specific about it, say you had a metastatic breast cancer to the liver. You could have a liver biopsy done and that tissue from the liver biopsy could be sent for genomic testing. There are a lot of companies that do this and there are also some larger cancer centers that actually do in house testing for genomics. So, this testing can be done and what it does then is, it helps you determine, do you have a biomarker that predisposes you to a certain treatment.

So, if that metastatic liver tissues, for example contained high levels of PBL1 expression for example and you were triple-negative, that would say to your doctor, “Ooh, this is a great candidate for immunotherapy along with chemotherapy.” Or if you’re estrogen-positive, for example, and your tumor contains a mutation in the gene called PIK3CA and that might make you a candidate for a drug called, alpelisib (Piqray). So, these mutations could often be paired to a drug or treatment options, or sometimes to a clinical trial to allow patients to come take advantage of more targeted therapies.

That sometimes, because they’re targeted, have fewer side effects than drugs that are a little more discriminate.

Katherine:

Marie sent in this question prior to the program. Are there some genetic tests that’re more accurate than others?

Dr. Meisel:

That’s a good question. I would say most genetic testing platforms have been heavily vetted and approved by national organizations and laboratories that’ve been tested multiple times before they’re allowed to be marketed. So, I wouldn’t say that one genetic testing program is necessarily better than another. I think that any of the commercially available platforms that’re used are probably pretty accurate.

Katherine:

Okay. How does symptom management play into the treatment decision?

Dr. Meisel:

I was just going to add one thing to that, if that’s okay. I was going to say that I think it’s important when you’re using genetic testing platforms though to know what you’re testing for. So, there are some platforms that will just test for say, the three most common mutations in BRCA1 and BRCA2 that Ashkenazi Jews have.

And so, if you get that testing back and you’re negative, you might think oh, I don’t have a mutation in those genes. Well, we know from that testing, just as an example, is that you don’t have a mutation in those three alleles of that gene. But if you haven’t had full gene sequencing, you could have a mutation somewhere else in that gene. So, I would say all genetic testing that’s commercially available is probably pretty accurate. But it is important when you get testing done to know what you’re testing for and what you’re not testing for so you can interpret your results accurately. And genetic counselors, as well as your doctors can help you do that.

Katherine:

Right, right. Okay, I’m going to ask the question, this question again. How does symptom management play into the treatment decision?

Dr. Meisel:

I think symptom management is huge, because like I said and I tell this to all my patients at the outset of treatment that most of the time, metastatic breast cancer becomes a chronic diagnosis for a patient. You’re dealing with it, essentially like a chronic illness for the rest of your life. And you’re on some form of treatment for the most part, for the foreseeable future.

And so, making sure quality of life is as good as it can be is critically important. And I think symptom management is a huge part of that and we know that if we can treat and manage symptoms well, people can live better and often live longer because then they can stay on treatment for more extensive periods of time comfortably. And so, I always encourage patients, don’t be a martyr.

Don’t think you have to just bounce in here and tell me everything’s okay if it’s not okay. If you’re having symptoms and side effects from treatment, or from the cancer, I want to know about them so that we can really aggressively manage those symptoms just like we’re aggressively managing the cancer. A lot of times oncologists can do that on their own. We are pretty well versed in managing a lot of symptoms and side effects.

But a lot of times also, there are teams of doctors either who do palliative care or here at Emory, we call it supportive oncology where they are specially trained in things like pain management and managing more common side effects like nausea, constipation, diarrhea, appetite suppression, that can go along with cancer and with treatment.

And then they often will co-manage patients with us as well, just to make sure there’s that really strong focus on maintaining as much of a low symptom burden as possible.

Katherine:

So, you mentioned earlier, clinical trials. When should patients consider participating in a trial?

Dr. Meisel:

I think it’s a great question and I think the answer is really, almost any time. There are trials in every setting. So, I think one of the common misconceptions about clinical trials is that you really only should be in a clinical trial, or your doctor might only mention a clinical trial if they don’t have other options for you or if you’re really in stage. And I think that perception is changing. But I think the reality is that there are clinical trials in every setting.

So, we have clinical trails looking at prevention of breast cancer. Clinical trials looking to optimize early-stage treatment of breast cancer. Clinical trials looking at secondary prevention, so once you’ve had breast cancer, how can we reduce your risk of recurrence. And then lots of clinical trials in the metastatic setting both for patients who are initially diagnosed with metastatic breast cancer.

And then in second, third, fourth line and even for patients who have had tons and tons of additional therapy that we’re looking at new drugs for. So, I think at almost any juncture where you’re making a treatment change, it’s probably appropriate to say, would there be a clinical trail that you can think of that would be good for me in this setting? And it may be that there’s a one that’s 12 hours away, and it’s not convenient for you or feasible.

And it may be that your doctor doesn’t necessarily know of one but then that prompts them to ask a colleague who may be more involved in clinical trial design and development. Or it may be that there is one, but you ultimately choose not to pursue it because you have a different option. But I think it’s always appropriate to ask, would there be a trail for me? Because if there is, then maybe that opens up an option you hadn’t thought about before.

Katherine:

Sure. For patients who aren’t familiar with the stages of clinical trials, would you give us a brief overview of the stages?

Dr. Meisel:

Yeah. Absolutely. So, in terms of clinical trials that’re being done in humans, we talk about Phase I, Phase II and Phase III typically. So, a Phase II clinical trial is typically an earlier stage trial.

Looking at either a drug that has not been tested in humans before or a drug that has not been tested in a particular combination in humans before. And so, those trials are done only in select institutions, usually academic institutions as opposed to private hospitals. And they often have what’s called a dose finding phase and then a dose escalation phase. So, the earliest part of those trials is actually looking at, what is the safest dose to give to patients?

So, they start the first patients at a low dose of the compound. And if those patients do well, the next patients that’re enrolled get enrolled at a slightly higher dose. And then up until they reach the highest dose they can find where people are tolerating it and doing reasonably well. And in those Phase I trials, doctors and investigators are also evaluating efficacy, is this drug working. But the primary goal of the early phase trial is actually to find the right dose to then study in larger groups. And so, if they find the right dose and there’s good biological rationale for the compound, then the trial would go on to a Phase II.

Which might be just what we call single arm Phase II study, where every patient is getting that experimental drug. And we monitor them to see, is the drug effective, or is it less effective than the standard of care? Or sometimes they’re what we call, randomized Phase II trials where patients are randomized to either get the experimental drug, or to get what the standard of care would be in that situation. I think a lot of people get afraid about the idea of a randomized trial because they’re afraid they’re going to be randomized to a placebo. And that is really not done in the metastatic setting, because it wouldn’t be ethical to give a patient with active cancer a placebo.

So, usually the randomization would be either to the study compound or to a standard of care drug. And then if things look good in a Phase II trial, then a Phase III study is done which is usually what the FDA requires to allow a drug to go on and be administered outside of a study for approval. And those Phase III trials tend to be larger studies that’re done in larger groups of patients with more statistical validity because of their size, to determine, is this drug really better than the standard.

Katherine:

Right. We have another question we received earlier, this one from Eileen. She asks, how will I know whether my treatment is working?

Dr. Meisel:

That’s a really good question. So, I think for patients who have symptoms from their cancer, they often will know the drug is working because their symptoms improve. Say if you have lung metastases and you are short of breath and your shortness of breath gets better. That’s a really good sign that the treatment is working. I would say that often what we are doing, and it depends a little bit on the regimen and what the patient is getting and how often they’re coming in.

But we’re checking labs as well and sometimes there are lab abnormalities when a patient is diagnosed with metastatic cancer that can then improve over time. So, for example, if someone has a heavy burden of bone involvement with breast cancer, there’s a lab value called the alkaline phosphatases that will often be elevated. If that starts elevated and comes down, that’s a really good sign. And some of their liver function tests that we check and if a patient has liver metastases, we often will see those come down if a patient is responding.

There are also, what we call tumor markers that we can check in patients with metastatic breast cancer. Those would be proteins in the blood basically that can be made by the breast cancer in abundance. And those are called CA27-29 and CA15-3. Some doctors check both of them. Some will just check one depending on which one their laboratory at their institution is running. But typically, I will check those at diagnosis of metastatic disease. And then if it’s elevated, I know it’s a good marker to follow for my patient. And then I’ll follow that monthly or every three weeks, depending on when the patient is coming in to see me.

And if I see that marker start to go down, it’s not an absolute, but it can be a good early indicator of improvement with the treatment. And then I think it varies a little bit from practice to practice and based on patient preference. But often there will be scans done when a patient is initially diagnosed to determine the extent of the disease. So, usually a CT scan of the chest and the abdomen and the pelvis or a PET scan, which some of you may have heard of. Either one of those is good.

And that can be done about every 12 weeks usually in the beginning, to make sure a patient is responding and once you feel confident that they are, those can be done sell frequently. So, I would say the scans and the lab work and then the patient’s overall condition are usually the way that we look to see, are we having a response or not.

Katherine:

We’ve talked about several key tests. Some patients may be confused about whether they’ve received these tests. So, what questions should they ask their physician to make sure they’re getting appropriate testing?

Dr. Meisel:

I think it’s probably useful because not everybody needs every test, and I think there are often things you hear about online or from friends or even in a webinar like this, and there may be a good reason why you haven’t had that particular test. So, I wouldn’t assume that if you haven’t had everything that we’ve talked about today even, that someone’s made a mistake or that you need that and aren’t getting it. But I would ask. I think it’s always helpful to know more, knowledge is power. And so, if you have never had a CT scan or a CA27-29 level or a genomic testing.

I think it’s not a bad thing if you’re curious about it, to just ask your treating team, “Hey, I heard about genomic testing, is there a reason I haven’t had that? Or have I had that?” Maybe you have, and they called it something else. I think it is complicated, but I think it helps to understand what you’ve had done and what you haven’t had done. And sometimes, asking about something like that may prompt the team to do things that my benefit you.

Katherine:

Before we wrap up, Dr. Meisel, how do you feel about the future of breast cancer research and what would you like patients to know?

Dr. Meisel:

Yeah, I think one of the most important things and I actually said this to a family this morning where a loved one had received a new diagnosis of metastatic breast cancer is that the field has evolved so much over the past five years. I think often when people get a diagnosis of metastatic breast cancer, it’s the most dreadful feeling they ever had. They remember that day for the rest of their lives. But we are seeing so many people do so well for so long now and tolerate treatments well because the treatments are better tolerated.

And there’s I think more attention being paid now to symptom management. That people really can do so much better than they’ve been doing. And I would say really, every year, even every six months, when I go to give a lecture on a topic in metastatic breast cancer, I can’t just give the same talk. I’m always having to update my slides because there’s so many new things coming out, so much new research on the table.

And we’re seeing so many new drug approvals now that we’re starting to unlock some of these new mutations and reasons for progression and understanding new drug classes. So, really think it is a bright time to be in breast cancer research, and there’s never been a better time to be a patient if you have to fall into that category.

Katherine:

It all sounds so promising, Dr. Meisel. Thank you so much for joining us today.

Dr. Meisel:

You’re so welcome. Thank you for having me.

Katherine:

And thank you to all of our partners. If you would like to watch this webinar again, there will be a replay available soon. You’ll receive an email when it’s ready. Also, don’t forget to take the survey immediately following this webinar. It will help us as we plan future programs.

To learn more about breast cancer and to access tools to help you become a proactive patient, visit PowerfulPatients.org. I’m Katherine Banwell, thanks for joining us.

 

Metastatic Breast Cancer: Accessing the Best Treatment For YOU

How could genetic testing results impact your metastatic breast cancer treatment options? In this podcast, Dr. Julie Gralow will discuss essential testing, the latest targeted therapies and emerging breast cancer research.

About the Guest

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: https://www.seattlecca.org/providers/julie-r-gralow.

What Factors Help Guide Metastatic Breast Cancer Treatment Decisions?

What Factors Help Guide Metastatic Breast Cancer Treatment Decisions? from Patient Empowerment Network on Vimeo.

What treatment is best for your metastatic breast cancer? Dr. Halle Moore of Cleveland Clinic reviews important considerations when choosing a therapy, including the role of molecular testing.

Dr. Halle Moore is Director of Medical Breast Oncology at the Cleveland Clinic. Learn more about Dr. Moore, here.

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Transcript

Dr. Halle Moore:

For patients with advanced breast cancer, some of the major factors that affect our treatment decisions are first the receptor results. This includes the ER and PR, which are the hormone receptors, as well as HER2. These receptors really guide the initial treatment options.

In addition, the patient’s overall health status is an important factor in treatment decisions. And then the prior treatment history, what the patient has previously received, either in an earlier stage of disease or previously for their advanced cancer.

Molecular testing for metastatic breast has gone from something that was primarily used only in the research setting to something that is now quite valuable in making treatment decisions every day in the clinic.

The results of molecular testing may indicate whether our patients are eligible to receive certain treatments, such as immunotherapy or certain targeted cancer treatments. We also have an increasing number of clinical trials that are testing treatments targeted to the molecular drivers of an individual’s cancer.

I would say one of the most interesting new approaches in the treatment of metastatic breast cancer is the use of antibody drug conjugates. These combine an antibody against a target that’s likely to be present on cancer cells more so than on normal cells in the body.

And, typically, a very potent chemotherapy drug is combined with the antibody. The antibody then allows for delivery of a high concentration of this chemotherapy drug preferentially to the cancer cells allowing for very effective treatment of the cancer while limiting toxicity from the treatment to the rest of the body.

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.

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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.

 

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.

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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?”

How Genetic Mutations Affect Metastatic Breast Cancer Prognosis and Treatment

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

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

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

See More From INSIST! Metastatic Breast Cancer

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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.