The Urgent Need for Triple-Negative Breast Cancer Breakthroughs with Dr. Elisa Port
By BCRF | March 1, 2022
By BCRF | March 1, 2022
There’s no one-size-fits-all approach to targeted breast cancer therapies. Breast cancer subtypes all behave differently from each other. We know better therapeutic strategies are desperately needed for triple-negative breast cancer (TNBC), an aggressive form that lacks targeted therapies, making it especially challenging to treat.
To mark Triple-Negative Breast Cancer Day this year on March 3, we dove deep into the science of TNBC with BCRF investigator Dr. Elisa Port, whose BCRF supported research focuses on this subtype.
Dr. Port is chief of breast surgery of the Mount Sinai Health System and director of the Dubin Breast Center at Mount Sinai Hospital in New York. Dr. Port, BCRF investigator Dr. Hanna Irie, and their teams are working to combat drug resistance in TNBC by developing a drug for the protein PRKCQ—a promising therapeutic target that may make TNBC more responsive to chemotherapy.
Chris Riback: Dr. Port, thank you for joining. I appreciate your time.
Dr. Elisa Port: Thank you for having me. It's always a pleasure to be here.
Chris Riback: First, you're a very well renowned surgeon, of course, and scientific researcher. So obviously it only makes sense that in college, you double majored in Spanish and French. I'm sorry. Dr. Port, did you take a wrong turn when you walked down the stage to get your diploma?
Dr. Elisa Port: So, I was not one of these people who was so goal-oriented, driven, directed early on in life. Yes, I was very achievement-oriented. Of course, I got good grades all through high school and college, et cetera, but I actually did not start out knowing what I wanted to do. My father was a doctor and I had of a cousin, who's more like a big brother to me, who's a doctor as well. So I definitely had my role models, but I wasn't sure. I spoke Spanish growing up and I thought that was a were important skill to have. And I found that I had a facility with languages and wanted to develop that. And the college I went to, Dartmouth, had a really incredibly well-developed language program. So I really wanted to take advantage of that somewhere along the way the pre-med courses sort of fell off the language courses. I know this sounds incredibly passive, but it's the truth of how it happened and the language courses just kept getting added on. I really enjoyed them more and more.
And in the end, I graduated as a language major and I had not really completed my pre-med requirements. I just kind of let them ebb way, which meant that a year or so later after floundering around in the real world, when I decided maybe medical school was a more directed approach and something that I would want to do. And yes, I can always use my language skills in that. I actually did have to go back to school to complete pre-med requirements and I did that in an extra year. And, I did that in kind of an expedited plan and then applied to medical school. And obviously, the rest is history.
Chris Riback: It's a terrific history. And I mean, that's a great and helpful story for many of us, I think of all ages. First, how many of us can empathize and recognize that there's not a straight path in life and that often happens. And the patients that we're going to talk about that you deal with many may, if not all of them, might be facing situations that don't offer the straightest path that they thought that they might have had. And there's a lesson there. And two, and maybe we'll talk about this as the conversation goes on, but among your skills, and you've written a book outside of just a scientific medical textbook, is your ability to connect with patients and understand that human component that goes beyond the purely scientific, purely medical, purely here's your diagnosis. Thank you very much. See you later. And I can only imagine that on some level that all connects and goes back to your earliest days of hola and bonjour.
Dr. Elisa Port: Well, listen, I had a very clear understanding early on, I grew up in San Diego, California. My house was about a 25-minute ride from the Mexican border. And there was an incredible Mexican influence. And we would go down to Mexico for dinner. And a lot of time there, vacation there, had many friends. And when I say Mexican, I don't mean of Mexican heritage. I mean, people who, my family worked with whatever, who lived in Mexico and would come across the border every day into the states for work and vice versa. so that was a huge cultural influence for me, and I just found that thankfully speaking Spanish and learning Spanish came naturally, but I just also found it to be, I think for a doctor in the United States, speaking Spanish is one of the most useful skills you can have practically speaking again, to your point Chris, connect with people and meet them on their own terms.
I don't use one iota of organic chemistry or physics anymore, but I can tell you, I use my Spanish on almost a weekly basis, and I love that and I love that we're able to connect. I just think, this is a bigger statement, but I just think in America, we are so used to everyone speaking English for us. And if you get outside the United States, it's just incredible how you can travel anywhere and, thankful for Americans that most people do speak English because most of us don't speak a second language. And I think that's a shame.
Dr. Elisa Port: And I found that when we travel and we speak the native language, whatever that is, even my very rudimentary now French is a use it or lose it kind of scenario. And let's just say, I have not had the opportunity to use it the way I do Spanish. It's just lovely to be able to, again, when you travel to these countries to speak the native language.
Chris Riback: Well, there's another great lesson out of that that comes from many of these conversations that I've had with other scientists, researchers, doctors like yourself is this work is going on all over the world. I want to get into your research, particularly around the triple-negative breast cancer patients, but there was another item that struck me slightly more on point was a quote of yours that I came across where you said in, "In 2020 women diagnosed with breast cancer should have every reason to be optimistic." It's now two years after that statement, I'm betting you stand by it. Tell me why?
Dr. Elisa Port: Yes. More so than ever before, because what we've seen. One of the statistics, Chris, that kind of backs that up is between the year 2000 and 2010, the death rate from breast cancer dropped almost 2 percent each year. that's crazy numbers. That means that if you were diagnosed in 2011, 2012, you were 20 percent more likely to survive than if you were diagnosed in the late 1990s. That is a lot of progress in a very short period of time. And that trend just has continued strongly and it's owed to a variety of different factors, which continue to develop and title wave, which are improved diagnostics, improved technology and earlier diagnosis, so that we can catch these cancers earlier when they're way more treatable, way more curable. And then the second part of course, is research that has led to better treatment options than ever before.
At any given point, like at my center, I think we have 20 clinical trials going on in breast cancer, and that's just our institution where we're very, very heavily invested in research and cutting-edge care, the Dubin Breast Center and at Mount Sinai. Not all of those trials are going to translate into meaningful improvements, but some of them will. And so if you've got that many irons in the fire and that many options that are being explored, even a couple of them are going to translate into big breakthroughs for improvement for a group of patients that otherwise might have had might not have had other options.
Chris Riback: So, let's talk about the research and let's start with the broad perspective and what you are facing. Why is drug resistance such a particular challenge in triple-negative breast cancer? Why is the response to standard chemotherapy so highly varied and why do so few targeted therapies exist?
Dr. Elisa Port: Oh my gosh. These are our philosophical questions that if I could answer, I would probably be on the short list for some very big prizes.
Chris Riback: Well, we look forward to nominating you?
Dr. Elisa Port: God, no. This is like lifetimes of work. So let's just look at what triple-negative breast cancer is. Let's talk for a second to your point right before, which is the optimism related to breast cancer. And what I said about the improvement in survival between 2000 and 2010. So much of that, Chris was hinged on the develop of HER2/neu targeted therapy. When we say triple negative, what is the triple, and what is the negative? We now have moved past the one size fits all for breast cancer. We know that breast cancer is not just one disease. It's multi-different, what I call, subtypes. And each one of these subtypes behave so differently from each other. They're almost like comparing breast cancer with colon cancer or colon cancer with ovarian cancer.
So, these subtypes are so different from each other and their treatment pathways and the option for treatment can really diverge wildly. So, the first order of business, when a patient comes into my office, newly diagnosed with cancer is, I say, the first thing you need to understand is that there's different subtypes of breast cancer. And how do we figure out what subtype you have? And the answer is it's really easy. Once a biopsy is done and it shows cancer, they run three tests on that tumor. They run a test for what's called estrogen receptor, progesterone receptor. And the third one is called HER2/neu. And together those three, that's the triple, help tell us and define for us what is making that cancer grow or tick.
So, when a tumor is said to be estrogen and/or progesterone positive, that means that hormones are feeding that cancer. It's helping the cancer grow, almost like hormones to a cancer is like water to a plant. And the reason why that's super important is that let's just agree, and it's super intuitively obvious that the more you know about what is making a cancer grow, the more options you have to intervene on that level. So, we have multitudinous different drugs that block cancer cells from seeing hormones that they need to grow. So, if your tumor is hormone positive, there's all these different me medicines you can choose from to block that stimulation from happening. So, it's like stopping to water the plant. What's going to happen if those tumor cells don't see these hormones? Many of them will wither up and die or implode. That's why being Esther and progesterone positive is a favorable thing because we know that that's the way the tumor is growing. And we have many of those options for treatment.
Chris Riback: You have ways to try to turn off the water.
Dr. Elisa Port: Yes, and target it. As you said, to your point about targeted therapy that is targeted therapy, this cancer is being fueled by hormones. We are going to block that. That is targeted to your tumor. The third one, the third component, HER2/neu, which is lesser-known is a protein that sits on a tumor cell. And when HER2/neu is positive, it used to be a very bad thing, because those were considered aggressive cancers. But flash forward to that decade we talked about 2000 to 2010. When a couple of, as you said, targeted therapies were developed to latch onto that HER2/neu protein and cause those cells to implode. That drug, the first drug of its kind, was called Herceptin and there have been others to follow. And basically, what that did overnight, Chris, was it used to be we'd see someone with HER2 positive breast cancer and go, "oh, oh no, that's kind of an ominous sign. We're going to treat you, but we don't know how this is going to turn out." Twenty years later, we're like, "We've got this medication that will most likely melt the tumor away so effectively that when we go to do your surgery to follow, there might not even be any cancer left." And so that's a third targeted therapy.
So, we have estrogen, we have progesterone, we have HER2/neu and we have very targeted therapies for all three of those markers. So, triple-negative breast cancer means estrogen negative, progesterone negative, HER2/neu all negative. That means that none of those things are known to be working or at play with the growth and perpetuation of this cancer. Doesn't make it not a cancer. The problem is we just know less about what is making grow and that's why the targeted options are more limited. And really the only option we have for those patients is a more generic form of chemotherapy.
Triple-negative breast cancers make up about 15 percent of all the breast cancers we diagnose, but they're disproportionately more common among certain groups like African American women. Black women, when they get breast cancer, 30 percent of their cancers are triple negative. Big problem. Women who have the BRCA1 gene, the BRCA1 gene, not the 2. If they get breast cancer, 75 percent of their cancers are going to be triple negative. And so, you have very specific subgroups of people who are at high risk for developing triple-negative breast cancer. And from me, that's sort of the last group where we don't have as effective options as the ones I described for the other groups. And that's where we still need to make more progress.
Chris Riback: What then is the protein PRKCQ, and why are you focused there?
Dr. Elisa Port: This is what we're researching, which is ways of figuring out and mechanisms of figuring out whether or not there are other tests we can do on the tumor to define, number one other targets that are drugable. And number two, if there's a way to predict which tumors in advance are going to be chemo-resistant and whether or not that chemo-resistance can be overcome. So together with my amazing researcher partner, Dr. Hanna, who we call Yoko, Irie, who's an MD PhD, and she's truly the brains behind the operation as it relates to the science recently discovered a compound that when given together with certain chemotherapies, that in certain tumors that were resistant to chemo alone. When you give this compound in combination, it almost like unmasks the tumor and makes it sensitive to chemotherapy.
One of the reasons why this work has been so important and is funded by BCRF, which we're incredibly grateful for, is that what our actual grant has allowed us to do is develop this incredible resource, Chris, which is these, what we call avatar models. So, what we've done is when a woman comes into our office and she has a diagnosis of triple-negative breast cancer, with her permission, we put her through another biopsy to retrieve tissue, additional tissue from the tumor, these before she gets any treatment. And usually what we do with that is we try to grow that tumor out and try a number of different chemotherapy agents biologically.
And what we've been able to do with our research has been in the patient we go ahead then and give chemotherapy. And what we've done is, of course, at the conclusion of chemotherapy, these people all get surgery. And that's when we see and measure the response to treatment, some women will have what's called a CR, the complete response, meaning we go to take the tumor out and it's all just scar, dead tumor cells. And some women will have residual cancer. And those are the people who, to varying degrees are what are called chemo resistant. And so now imagine you can take a piece of that tumor that's left over and compare it to the original and you know which patients are chemo resistant. And you can focus on those as a model for research in overcoming that chemoresistance.
Chris Riback: And in what stage are you at in this research. My understanding, and you'll correct me, please, if I have it wrong, is it's still lab work. Is that accurate? What is the status of the research?
Dr. Elisa Port: A hundred percent correct. It is lab work, but now that we've identified these druggable, these compounds, we are working toward developing a clinical trial.
Chris Riback: As I was thinking about that, and I don't know if this is a scientific question or an emotional one: How do you balance, perhaps in your own mind, the speed and urgency needed? You're trying to help triple-negative breast cancer patients with the care and time required to do research right. I know there are standards and rules and guidelines, and you have all of that. Still, getting that balance right, I'm sure you want to help every patient yesterday. How do you balance that tension?
Dr. Elisa Port: I don't think it's possible in the sense that the processes is the process, and there's only so much time that all of these processes take, and those are sort of the built-in limitations. You know, there's also resources too. Think about what's been done in public health, as it relates to, for example, look at how quickly a vaccine for COVID was developed. Billions of dollars were at it. And it does make me wonder, if you put a hundred of the best and brightest scientists in one room and threw some unquantifiable, ginormous amount of money at them to come up with one or two or three therapies for triple-negative breast cancer would it happen any quickly?
I do think all of us share a sense of urgency, and I don't think there's any complacency on our part or on the scientific community part. But, I would just look and say, yes, if breast cancer is the sum total of a whole circle and triple-negative breast cancer is sort of the last bastion of 15 percent, look at how much we've done with the sense of urgency over the last 10 to 15 years to improve outcomes. And yes, this is the remaining piece of the slice of the pie that require requires a lot of effort, energy, attention to have better options.
Chris Riback: You mentioned earlier, as well, the importance of recognizing, finding, identifying cancers early. Tell me about your research and for our listeners, we're doing this conversation via video using only the audio and I don't know how it [the conversation] could have gotten better, but it just did because Dr. Port just brought a terrific looking dog into the-
Dr. Elisa Port: This is my rescue. This is my Rooney, the rescue
Chris Riback: Rooney, the rescue. We are going to have to make this video because Rooney the rescue, think our audience would love to see Rooney.
Dr. Elisa Port: It's called pet therapy. I'm a big fan.
Chris Riback: Excellent.
Dr. Elisa Port: Both for me and our patients.
Chris Riback: Okay, well, if we hear a little bark now everyone will know why and it's no problem. Tell me about some of your earlier research and the role of MRI in patients at high risk for breast cancer and the role of PET scanning in breast cancer.
Dr. Elisa Port: So early on when I was in practice in the late 1990s and early 2000s, there was a huge explosion in tech technology and imaging. And I was very, very interested in, wanted to play a role in figuring out how to optimize the use of those technologies in our breast cancer patients and PET scanning was one thing. PET scanning is really whole body imaging to figure out if cancer has spread to other parts of the body. We don't use it in all patients, people with very early-stage breast cancer do not need a full-body scan. People ask that all the time to find out if the tumor is spread, but people with more later-stage diagnosis can often benefit from them to define how of the diseases and whether or not it has spread to other parts of the body.
PET had been used in other disease types and I was really interested to see if it was effective in breast cancer. I did a study really early on looking at the comparison of PET scan to, at that point what was standard of care imaging, which was CAT scan and bone scans, kind of old school. And what we found is that PET scans were a little bit better as it came. They were equal in detecting systemic disease, but they were better in the sense that it was one test instead of two tests. So putting patients through less hassle and all of those logistical nightmares of coming in for testing. It was also more, what's called, specific, meaning if the PET scan was positive, it was way more likely to be accurate, in that sense. We definitely also discovered that there were certain kinds tumors that it wasn't so great for. There's a subset of breast cancers called lobular cancers and PET scans don't work as well. Those tumors tend to grow less like a ball and more like a sheet. So, they could be really sneaky and PET didn't pick that up so well.
Those were all things we helped to define and then PET scanning came into, as a result of our work and many others, PET scanning did become kind of standard of care for a subset of patients with breast cancer. So I think I just played a small part in helping define what the utility was of PET scanning in breast cancer patients. As it relates to MRI, MRI has definitely now become one of the most common tests to be done in women with breast cancer.
And I looked at it in one study I did as how useful it was in screening women at increased risk for breast cancer. And we found in terms of picking up cancers that mammograms might miss. And like many, many studies that have been done, we added to the body of literature, showing that in certain more high-risk groups, MRI is very helpful in additive and screening. And mammograms alone are probably not enough. In other groups that are slightly elevated risk, but not as high, then MRIs may not be as much added value. And so it's really just all about exploring some of these new things that were coming online and trying to not one size fits all and throw the kitchen sink at everyone and really help figuring out who can benefit the most.
Chris Riback: Well, it was certainly interesting to read about that set of work that you did. And now the work with PRKCQ, which to a layperson feels totally different. But, then again, as we discussed earlier, you started your life in a totally different area, languages. So perhaps it's not surprising you have a flexible mind that can transition.
I have two questions that remain in my mind. One is positioned perfectly behind the delightful rescue [dog], Rooney, is your book, The New Generation Breast Cancer Book. That book now is, I think a couple of years old, maybe four or five years old?
Dr. Elisa Port: Yep. About five.
Chris Riback: About five, I'm sure, just as relevant today. Why did you write it? Who were you writing it for?
Dr. Elisa Port: Thank you for asking the question because the book was really a passion project. I never said, "Oh, I want to write a book and I want to do that." Really, it started because I felt like there was an unmet need and that there was a hole that kind of needed to be filled. And what I saw, Chris, was that as you and I talked about, the prognosis for breast cancer patients was getting better and better and better. and we had more and more to offer. And yet there was a total disconnect between that and women coming into the office newly diagnosed with more doom and gloom than ever before. For a very long time, it took me to process to figure out what was going on, why was everything I was talking about: We've done better than ever before, we have so much to offer you, and yet women were really, really coming in, like at their wits end.
And the answer I figured out was this exploding thing called social media and the internet which really is now 10, 15 years old as it relates to the level of access. And so what I started noticing is that the internet in particular is sort of a clearing house for, yes. Everyone says when you're diagnosed with breast cancer, get information, get information, but starting to be the problem was not lack of information. It was actually too much information with no filter. So when you are that person with early-stage breast cancer, as many are diagnosed with going online, you are seeing kind of the worst of the worst. And I equate it to like Yelp or like Expedia any of these places where you're having reviews. For the majority of women who have been breast cancer and go on and get their treatment and do really well, you don't see those people blogging and chatting anymore. They go on to live their lives.
So, by definition, what I was seeing is that if you aren't newly diagnosed and you are going online, there was a very curated selection of people who either had bad outcomes, more likely, who were desperate, who were filling these pages with really, really negative stories. And so when you're newly diagnosed and you're reading that and that's all you're seeing, it's a very bad place to come from. Onto top of it, of course, with email and texting and all those things, what was happening I found is that women would email a friend and that friend would send out an email to 10 friends and they would-
Chris Riback: Post it on Facebook.
Dr. Elisa Port: Yes, post it on Facebook, see this person, see that person, I heard this, I did a lumpectomy, I did a bilateral mastectomy. You need to use my doctor. And again, it's done under the: everyone's just trying to help. But to the point that we made earlier, one of the huge improvements with breast cancer is there is no one's size fits all. And so women were getting a lot of feedback and a lot of intel about other people's cases that may have nothing to do with theirs. And they were coming into the office saying, to the point about PET scanning, my neighbor told me make sure I get a PET scan. My sister told me tell your doctor to do genetic testing and not realizing again, under the auspices of everyone's trying to help, but not gets everything and all cases are different.
So, the book came out of the need for what I consider the hardest part for patients with breast cancer, which is from the moment they get the diagnosis, which is usually a phone call from their internist, primary care doctor, radiologist to the time where a set up an appointment with a breast surgeon to get a plan. And that's sort of the dark, the black hole, of scariness and lack of information where women are their most vulnerable and are at most risk for being taken down a rabbit hole of doom and gloom.
And so, I wrote the book. It is truly not at all patronizing, intense or paternalistic saying, don't go to the internet. It really was written as a kind of insulator, or a framework to give women sort of an overview and to give them sort of a calming background against which they understand that if they seek out this information, it may have nothing to do with them and to understand that until they get in to see a doctor, who can give them advice about their particular case, all of this stuff is kind of just background noise.
Chris Riback: What an outstanding insight that I'm sure all of us listening are extrapolating to all other parts of the internet and life and society, et cetera, but will hold that aside. But the insight that there's no longer a lack of information. On the one hand that's great, but what that has created though is a lack of a filter. And in particular, breast cancer, it is all about the personalization. There's a lot of information out there, but it's not filtered, it's not customized, it's not personalized. And that's a great insight and a great help. To close out: BCRF. What role has BCRF played in your research?
Dr. Elisa Port: Well, BCRF has played a huge role in my research. Number one, of course, the funding of this research, which I think is going to be groundbreaking over time. I think some of the discoveries that my partner Dr. Hanna Irie has made, and that I've been privileged to be involved with really have legs. And I think that that's obviously number one, two, and three on the list, the funding of really critical research and the idea of the cache of the BCRF researchers selecting out the top performers and the minds that have the most promise and the most likelihood of changing the playing field and delivering transformational options to our patients. And they're really selecting those people out.
And I think the second part is actually what some people don't get to see is the collaboration between us. I think the sad part of COVID is obviously we haven't all gotten together and reunited in the way that we did, but the summits and the retreats and the discussions and the collaborations that have been developed out of these things, those are priceless. And those are incredibly important to furthering the end goal, which is more options for treatment, better options, a cure. People say, "Well, when will breast cancer be cured?" And the answer is: It is already being cured. Lots of women, the majority of whom get breast cancer are cured. Our goal is to cure all women. And we're not there yet.
Chris Riback: Not yet, but with the work that you're offering, Dr. Irie and others, someday. Dr. Port, thank you. Thank you for your time. Thank you for the work that you and your colleagues do every day.
Dr. Elisa Port: Thank you so much for having me. I really enjoyed speaking with you and thanks for getting such important information out there.
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