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Precision Medicine (Transcript)
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[Narrator] Behind every heartbeat is a story we can learn from. As we have for over 80 years, Blue Cross and Blue Shield Companies are working to use the knowledge we gain from our members to better the health of not just those we insure, but all Americans. Some call it responsibility. We call it a privilege. "Second Opinion" is funded by Blue Cross Blue Shield.

 

[Announcer] "Second Opinion" is produced in conjunction with UR Medicine, part of University of Rochester Medical Center, Rochester, New York.

 

 

[ Applause ]

 

[Dr. Peter Salgo] Welcome to "Second Opinion," where each week a panel of medical experts comes together to discuss a real-life case. I'm your host, Dr. Peter Salgo, and I thank all of you for being here today. Our experts today are breast-cancer surgeon Dr. Laura Esserman, from the University of California San Francisco School of Medicine, and breast medical oncologist Dr. Alissa Huston from the University of Rochester Medical Center. And now I'd like you to meet our special guest -- Donna Haher. She is here to share her personal story.

 

[Donna] I'm Donna Haher. I'm 63. I love to play golf. And I love being around my grandchildren. They keep me young. And my health at this point is fabulous. You know, it was a normal day going in for my mammogram, which we all hate. [ Laughs ] And, you know, I didn't think anything of it. Then the doctor that was on staff came out. She introduced herself to me and said that she would like me to have an ultrasound. I knew there was -- it was -- you know, I had a tumor right then and there. I was -- I was calm.

I was sitting in the waiting room, waiting, and I was just calm because I knew if it was breast cancer, there was nothing I could do about it. So I just told myself I was gonna put my big-girl pants on and [laughs] accept the fact.

 

[Dr. Peter Salgo] Donna, thank you so much for being here. So, you had the ultrasound.

 

[Donna] Yes.

 

[Dr. Peter Salgo] What happened after the ultrasound?

 

[Donna] They told me that they found a tumor and they needed to do a biopsy.

 

[Dr. Peter Salgo] First of all, let me ask you this -- do you have any family history? Anyone in your family have breast cancer?               

 

[Donna] No.

 

[Dr. Peter Salgo] Okay. So, you went ahead. You got the biopsy.

 

[Donna] Yeah.

 

[Dr. Peter Salgo] Right. And although you had a suspicion, now what did they confirm?

 

[Donna] They told me I had stage I breast cancer.

 

[Dr. Peter Salgo] Now, your husband's in the audience. Michael, what was it like for you to hear that your wife had breast cancer?

 

[Michael] Terrible. I was on my way to pick her up. She hadn't told me yet. I got lost trying to pick her up. She's walking around in the snow. I finally got her in the car, and she let me know what was going on. And it was devastating. Very, very hard to explain the thoughts that I had. It was just -- I looked at the

future, wondering how we were gonna get along and what was gonna happen to my wife.

 

[Dr. Peter Salgo] Donna, that's got to be hard to hear, isn't it?

 

[Donna] Yes.

 

[Dr. Huston] I think what happens is you see the difficulty when someone's faced with a new diagnosis, and there's that loss of control for you as the individual -- and then especially for their partner or provider. And so it can be difficult. And I think part of what we do is trying to help people work through that and figure out what ways can you begin to take some of that control back.

 

[Dr. Peter Salgo] But, you know, it used to be a lot worse.

 

[Dr. Huston] Mm-hmm.

 

[Dr. Peter Salgo] And as medical science has progressed, there's a new phrase involved with breast cancer, breast-cancer treatment, called "precision medicine." What is that? And how does that impact breast cancer and survival and what you should be thinking if you hear the diagnosis?

 

[Dr. Esserman] So, I think it's so important for any woman to understand that breast cancer is not one disease. In fact, it is a whole spectrum, a whole range of disease, and it can be -- Just like if you have an

allergic reaction, it could be as simple as a hive or a rash and as terrible as an anaphylactic shock. So, breast cancer comes in many forms. It can be very mild -- we use the word "indolent," or ultra-low-risk -- all the way to something that's super aggressive. And they are not the same. They're not treated the same anymore because we have the ability to tell what's what. So, the most important thing that I tell, that every woman should know is that if you get a diagnosis, even if you're told you have an abnormal mammogram, stop, take a deep breath. You have plenty of time to get information.

 

[Dr. Peter Salgo] What I hear mostly from folks like you -- in fact, I've read your stuff -- is you've got to take into account the woman's genes -- we're talking mostly about women -- and also something else, which we never were able to do before – the genes in the tumor.

 

 

[Dr. Esserman] Mm-hmm.

 

[Dr. Peter Salgo] What does that mean?

 

[Dr. Esserman] So, it turns out there are a number of these molecular tests or multi-gene tests that really give us a portrait of what that tumor is like and what that behavior is. There's several of them on the

market. They can help you understand how much risk there is. Some tell you what's your risk after you've had hormone therapy and they're specifically for people of hormone-positive disease. Then there's some tests that really look across all of the breast cancers.

 

[Dr. Huston] The goal, as I see it, is really to figure out and tailor precisely to the patient what treatment is going to be best for them. So, we already heard and agree there's so many different types, that breast cancer falls on a spectrum of risk. And you could have two cancers the same size, and they're gonna behave very differently in one individual versus another. And so what I look at is how we can use these tests, along with everything in our pathology report, to determine who is gonna get a benefit from chemotherapy, who is at higher risk for recurrence, and that helps us tailor our treatments to the individual.

 

[Dr. Peter Salgo] Now, I've heard -- and I'm sure you hear a lot more than I do -- the following mantra --"I've got cancer."

 

[Dr. Huston] Mm-hmm.

 

[Dr. Peter Salgo] "Get the stuff out now. Hit it. Hit it with chemo. Hit it with radiotherapy."

What's wrong with that approach?

 

 

[Dr. Esserman] Because if you don't need all that, why do you want the toxicity? I mean, who would want

chemotherapy if it wasn't going to benefit them? Not everyone needs radiation. And when someone has an abnormal mammogram, not everybody needs a biopsy. Not everybody needs surgery. And, in fact, if you have a very aggressive cancer, doing surgery first is not the right thing to do. I'm a surgeon. I know how to use my craft wisely.

 

[Dr. Peter Salgo] Donna, when you had your diagnosis, walk us through what happened. What did you do next?

 

[Donna] Well, I went in to the surgeon's office. And I basically told her, "We have to get this out. We have to have surgery right away because I go to Florida for winter and I play golf."

 

[ Laughs ]

 

 

[Dr. Peter Salgo] What did you and your surgeon decide to do? And what eventually did you and your surgeon come to a decision about?

 

[Donna] She told me that I could -- she would do the surgery and that I could go to Florida and have my treatment.

 

[Dr. Peter Salgo] So, you had a lumpectomy...

 

[Donna] Yes.

 

[Dr. Peter Salgo] ...with some lymph nodes, a lymph-node dissection.

 

[Donna] Right.

 

[Dr. Huston] Sentinel node.

 

[Dr. Esserman] Sentinel nodes.

 

[Dr. Peter Salgo] I understand that, at surgery, what they found was something called IDC, stage I -- I cheated, I know this --

 

[Donna] Right.

 

[Dr. Peter Salgo] Stage I with clear margins.

 

[Donna] Right.

 

[Dr. Peter Salgo] All right. What's that?

 

[Dr. Esserman] Well, that doesn't tell you all that much, you know? IDC stands for "invasive

ductal carcinoma.” All that means is the tumor cells that are growing in the milk duct have invaded into the tissue around it. So, what -- You have to look for what the receptors are. We look at several receptors on

the cell's surface. We look for estrogen receptors, progesterone receptors, and another marker called HER2 because these actually helped direct the kinds of therapies you might get. There's several molecular tests, of course, that you can send off.

 

[Dr. Peter Salgo] Now, they did make a decision before knowing all of that -- because they didn't have the tissue to send out -- as to whether to do a mastectomy or a lumpectomy and a sentinel lymph-node dissection. What affects that decision?

 

[Dr. Esserman] So...you know, there are -- It used to be that all we did was the mastectomy, and we would remove the whole breast. In fact, we started by doing radical mastectomies. And we soon learned that that actually wasn't any better than doing a modified radical mastectomy, and that really wasn't any better than doing a lumpectomy and radiation. And in certain circumstances, now we know that's not better than just doing a simple lumpectomy. And I think the story of surgical advances in breast cancers really follows the advances in science and our way to apply it in a way to start doing less and to doing less safely. If someone comes in with a very big cancer, that doesn't necessarily mean they have to have a mastectomy. Someone with a big cancer, as I said earlier, we're gonna treat with systemic therapy first.

And if you can shrink it and make it go away, you can do much less surgery.

 

[Dr. Huston] I think with all of the different advances that we have, I mean, we're just better able to improve how we approach treating patients and what their -- what options we can offer them and what their, then, outcomes are by being able to better identify which treatments and spare patients the toxicity

of certain therapies that can cause harm in the long run. As we were saying earlier, chemotherapy can cause...

 

[Dr. Peter Salgo] Yeah. Trouble.

 

[Dr. Huston] ...trouble.

 

[Dr. Peter Salgo] Mammograms.

 

[Dr. Huston] Yeah.

 

[Dr. Peter Salgo] They find all these really early cancers. That's why the death rate is down, right?

 

[Dr. Esserman] That is definitely one of the reasons why the death rate's down. And, you know, no one --

You know, again, when you do any kind of intervention, what you have to do is learn. And one of the things we learned is that one of the things that changed was we had a big increase in these early-stage

cancers, but we didn't have a concomitant drop in late-stage cancers. So that meant that we're finding

more of these early cancers. And many of these early cancers aren't necessarily going to kill you, so we have to really think about, can we define this ultra-low-risk type of cancer? Is that possible? And it's something that, you know, I've been working on for a decade.

 

[Dr. Peter Salgo] You know what that requires?

 

[Dr. Esserman] What?

 

[Dr. Peter Salgo] An awful lot of wisdom.

 

[Dr. Esserman] It does.

 

[Dr. Peter Salgo] There's a study out there called "WISDOM." It just so happens it's yours. Tell me about it.

 

[Dr. Esserman] Yes. So, we know that one size doesn't fit all for treatment. How could it be that one size should fit all for screening? So, what we are trying to think about is -- You know, we need to make advances in screening by really applying what we've learned about treatment and what we've learned about risk. So, what we need is a modern-era screening trial, where we can start to understand who is at

risk for what kind of breast cancer.

 

[Dr. Peter Salgo] So, that's what you're doing.

 

[Dr. Esserman] Right. Exactly. And as you know, there are many recommendations for how to screen.

There are some in the camp where annual screening is thought to be best and some in the camp where people think you should be getting every other year a screening, starting at 50. So, when there's that much controversy, it's time for a study. But instead of just testing annual versus every other starting at 50, what about saying, "Let's do -- Let's test personalized screening. Let's figure out all the factors that -- that -- that determine someone's risk, the best we know today, and keeping improving that as we go. Your breast density, your age, whether you've had a biopsy, what your genetic -- what genes you've inherited, and try and use that to say, "Okay, let's now determine your risk and therefore assign you when to start, when to stop, how often to screen, and with what modality."

 

[Dr. Peter Salgo] Well, that's the purpose of a study, right?

 

[Dr. Esserman] That's the purpose of a study. So, we are trying to screen 100,000. We're trying to recruit 100,000 women. And we offer them the chance to participate and share their wisdom.

 

[Dr. Peter Salgo] All terrific. In the meantime, you had your surgery. You're in Florida. You're waiting for results. What's going on with you?

 

[Dona] Just waiting. I was playing golf, and I was waiting. Dr. Huston called and told me that the test came back and it was 3%.

 

[Dr. Huston] Mm-hmm.

 

[Donna] No question -- I don't need chemo.

 

[Dr. Peter Salgo] Well, that's good. What did she recommend?

 

[Donna] Radiation.

 

[Dr. Peter Salgo] Okay. Tell me about that.

 

[Donna] I had 19 treatments of radiation, one every day, five days a week. By Friday, I was tired. Saturday, I slept on the couch.  [ Laughs ] Sunday, I'd get dressed and we'd get in the car and we'd go sit by the water and have breakfast. And then Mike would just drive, and we'd drive around Sunday. And then I'd start all over again.

 

[Dr. Peter Salgo] What does precision medicine -- We've explored precision medicine in terms of screening...

 

[Dr. Huston] Yes.

 

 

[Dr. Peter Salgo]...in terms of decision for treatment. Now it's post-surgical treatment. How do you integrate this kind of precision medicine into this kind of decision making?

 

[Dr. Huston] So, I think that's where a lot of these specific profiling tests really come into play, that this is where they are used to really hone down who is gonna get the benefit from chemotherapy. And there's several of these tests that are out there, that can be used.

 

[Dr. Peter Salgo] What are you looking for?

 

[Dr. Huston] We're looking for the risk of the cancer recurring in a different part of the body, and we're also looking at how much benefit that individual is going to receive from both the hormone-blocking therapy and chemotherapy. When I describe it to patients, I often say we want to stack all of our benefit. And how much the addition for many patients of chemotherapy on top of an estrogen blocker is going to give them really will then help us determine what's best for that person.

 

[Dr. Peter Salgo] The names that people here -- there's Oncotype, MammaPrint.

 

[Dr. Huston] Yes.      

 

[Dr. Peter Salgo] There's something called EndoPredict.

 

[Dr. Huston] Which is the newer one.

 

[Dr. Peter Salgo] What are these things?

 

[Dr. Huston] So, Oncotype has been around the longest, and that's a genetic panel of the tumor. That's what Donna had. And that really gives us an idea of, what is the risk of the cancer recurring? We get a score, and it --

 

[Dr. Esserman] With hormone --

 

[Dr. Huston] With hormone therapy. Exactly. That's the one caveat, is that this is with those that are taking hormone-blocking therapy. And, really, it's looking at how much additional benefit chemotherapy may provide on top of that hormone-blocking therapy. MammaPrint is -- And it divides, actually --the Oncotype -- into three risk groups. So, you can be very low-risk, with a low chance of benefit and very little benefit from chemotherapy, or high-risk, with a higher risk of cancer returning, but a large proportionate benefit from chemotherapy, or in the middle, where then we use some of the other clinical factors from the pathology...

 

[Donna] Right.

 

[Dr. Huston] ...to determine where people fall. And there's actually several large studies that are looking at people who fall in that middle group. They randomize them to chemotherapy or no chemotherapy. And we're waiting -- although we hear it will be presented soon -- on the updated data set from that.

 

[Dr. Peter Salgo] Donna, after your radiation therapy was done, you were started on medication, and what

was that medication?

 

[Donna] It's -- I still don't know the name of it.

 

[Dr. Huston] It's aromatase inhibitor -- Arimidex.

 

[Dr. Peter Salgo] Called anastrozole?

 

[Dr. Huston] Anastrozole.

 

[Dr. Peter Salgo] And what is anastrozole?

 

[Dr. Huston] So, what it does is after -- You know, we think about how hormones are made in our bodies

in different ways, and when someone's gone through menopause, there still is this level of estrogen that is made. And this basically reduces that estrogen in the body. Tamoxifen was the drug for decades that we used, but this is the next generation of what we recommend for those that have gone through menopause.

 

[Dr. Peter Salgo] And the side effects?

 

[Dr. Huston] The side effects -- it does have side effects. Everything has side effects, unfortunately.

 

[Dr. Peter Salgo] Why is she giggling?

 

[Dr. Huston] She's giggling. Hot flashes, which can happen, right? You're reducing estrogen in the

body, and so certainly hot flashes. A significant proportion of women report joint aching, and so there's been a lot of work looking at why that may be and ways that we can approach that and manage that in individuals, so we do a lot of counseling up front 'cause that can be a big quality-of-life factor. If you're taking a drug to help reduce your risks and then you're feeling achy and not able to move, that's not helpful overall in terms of your quality and functionality. And then it can also thin the bones, is the other really big one that we talk about with patients.

 

[Dr. Esserman] And exercise, actually, is really important in reducing --

 

[Dr. Huston] It is.

 

[Dr. Esserman] For every aspect of health, but it also reduces your risk of recurrence.

 

[Dr. Peter Salgo] Can you just stop right there?

 

[Dr. Esserman] Yes.

 

[Dr. Huston] Yeah.

 

[Dr. Peter Salgo] Because I really want people to hear that.

 

[Dr. Esserman] Yeah.

 

[Dr. Huston] Yeah.

 

[Dr. Peter Salgo] Exercise. Non-specific, interesting stuff. Exercise.

 

[Dr. Huston] Exercise.

 

[Dr. Peter Salgo] And you're telling me that there's -- you believe or there's evidence...

 

[Dr. Esserman] There's evidence.

 

[Dr. Huston] There is evidence.

 

[Dr. Peter Salgo]...that if you exercise, your risk of recurrence goes down?

 

[Dr. Esserman] Exercising, breaking a sweat four times a week, makes a big difference. It actually reduces your risk of getting it, of progressing with it, and dying of it. So, it's actually something that's very important that people can do. And by the way, it's good for your health overall.

 

[Dr. Peter Salgo] You know, every show we've done, somebody brings up exercise, and every time, it's got an unexpected benefit...

 

[Dr. Esserman] Mm-hmm.

 

[Dr. Peter Salgo] ...whether it's heart disease, lung disease, breast --That's unexpected.

 

[Dr. Esserman] You know, and we used to tell people after a lymph-node surgery that they couldn't move their arm and they couldn't exercise. You know, they couldn't lift their arm. And it turns out, of course, that's wrong because exercise is good for everything else. And they finally did a randomized study, and they showed that you can reduce the chance of lymphedema by doing special, you know, arm-strengthening exercises.

 

[Dr. Peter Salgo] You're telling me that if you actually look at something in an organized way, you may get an answer?

 

[Dr. Esserman] That is correct [ Laughter] I'm all for that.

 

[Dr. Peter Salgo] I'll bet you are. We're gonna pause just for a moment. You know, every day, we hear about medical innovations that make an impact and hold promise for improving our healthcare. Just look what we've been discussing today. And now take a look at this.

 

[Hicks] Imagine if every patient with cancer, you could do a profile or a fingerprint that would allow you to understand, at a very fundamental, biologic level, how much of a threat that tumor was to that patient and tailor or design a treatment strategy that would be specific for that patient's biology. That's the direction cancer research is going in terms of precision medicine. [marimba music] When I started my career, the gold standard was really morphology and what the pathologists saw under the microscope. What I see here is this brown staining highlighting the membrane of these tumor cells. This looks like a HER2 overexpressing breast cancer. Using this particular technology, however, we can detect the presence of the protein, but I'm not able to give a precise amount. There's research data to suggest that if you could measure that protein, that information would be important and clinically actionable. Imagine this is a breast tumor cell. These little knobs represent the HER2 receptor. So, a breast tumor with a normal HER2 status would have a few of these knobs, approximately 10,000 to 20,000 on the tumor's surface. A breast with a HER2 alteration would have a marked increase in the number of receptors into the millions. We were approached a few years ago by a Japanese company that had developed a new technology, fluorescent nanoparticles that can be used to detect the amount of protein present on tumor cells and tissue sections. And if you look at it under fluorescent light, it's brightly fluorescent. You see these bright red dots all over the membrane of the tumor cells. There's too many for the human eye to possibly count, but with a computer, you could measure how many fluorescent particles are present on the membrane of that tumor cell. You know, I've dealt with this molecule for, gosh, close to 30 years. And I've thought about it a lot. But to actually look at a tumor cell, seeing this gross overexpression of HER2 demonstrated by these fluorescent spots, it was pretty remarkable. Here was an alteration that was evil, that contributed to a very aggressive clinical course for breast cancer. And our ability to accurately detect it gives us powerful information that can be used by clinicians to go after that and try to block it and shut it down.

 

[Dr. Peter Salgo] So, Donna, right now – how you doing right now?

 

[Donna] I'm doing great.

 

[Dr. Peter Salgo] You have breast cancer, and you're doing great.

 

[Donna] Yep. I had breast cancer.

 

[Dr. Peter Salgo] Mike, did you think we'd ever be right here at this point right now?

 

[Mike] Never. But when she came back home and she said that she was cancer-free, it was amazing. And I hope that happens to everybody that ever has this problem.

 

[Dr. Peter Salgo] I did promise we'd come back to one thing -- 'cause you were talking about cancers that are very aggressive...

 

[Dr. Esserman] That's right.

 

[Dr. Peter Salgo] ...cancers that are a little bit aggressive, cancers that are virtually not aggressive. So, my question is -- why use the word "cancer" for those tumors that may be no trouble at all? Wouldn't it be nice to have a lesion that we previously said was cancer, we now know is probably not all that dangerous,

and not use that "C" word?

 

[Dr. Huston] Oh, it would be great. I think it just -- The word "cancer" itself -- there is so much behind it. There's that fear and uncertainty when you hear that word. And we know that many of these will not transform over time.

 

[Dr. Peter Salgo] So, let me get a "yes" or "no" from each of you. What you've expressed is pie-in-the-sky. It would be great -- a future without or with very little metastatic breast cancer. Is there a chance, within the lifetime of people in this studio, we're gonna see it?

 

[Dr. Esserman] Five years.

 

[Dr. Peter Salgo] That wasn't "yes" or "no." It was better than that. And what do you think, Alissa?

 

[Dr. Huston] I mean, I do. I think that we are each day moving in that direction with a lot of the precision tests that we have, that we're just better able to hone down. So, I think it's in our future.

 

[Dr. Esserman] It is. It is in our future. But we have to have courage. And if we want a better future, that means everyone has to step up and do something different. You know, you can't expect to do the same thing over and over again and get a different result. But there are new drugs out there. There's new opportunities. We have to develop the trials and have people participate and send people to those trials so we can figure out how to find the right drugs for the right patient and to do it much faster and to develop less toxic therapies and be willing to let go of those things that we've always used, even if it makes us a little bit uncomfortable 'cause if you don't do something new, you're never gonna get that better future.

 

[Dr. Peter Salgo] Let's turn breast cancer into a chronic disease and a curable disease, if possible.

 

[Dr. Esserman] Mm-hmm.

 

[Dr. Peter Salgo] Everybody vote for that?

 

[Dr. Huston] Absolutely.

 

[Dr. Peter Salgo] I want to thank you. Donna, thank you so much...

 

[Donna] Thank you.

 

[Dr. Peter Salgo] ...for joining us today. I want to thank you guys. I want to thank everybody here in the studio audience, and I want to thank you at home for watching, as well. Remember -- you can get more second opinions and patients' stories on our website at secondopinion-tv.org. You can continue the conversation on Facebook, Twitter, and Instagram, where we are live every day with health news. I'm Dr. Peter Salgo, and I'll see you next time for another "Second Opinion."

 

[ Applause ]

 

 

[Narrator] Behind every heartbeat is a story we can learn from. As we have for over 80 years, Blue Cross and Blue Shield Companies are working to use the knowledge we gain from our members to better the health of not just those we insure, but all Americans. Some call it responsibility. We call it a privilege. "Second Opinion" is funded by Blue Cross Blue Shield.

 

[Announcer] "Second Opinion" is produced in conjunction with UR Medicine, part of University of Rochester Medical Center, Rochester, New York.