Did You Know That Your Tumor Might Change Over Time?

[00:00:00] Adam Walker: From Susan G Komen, this is Real Pink, a podcast exploring real stories, struggles and triumphs related to breast cancer. We’re taking the conversation from the doctor’s office to your living room.

[00:00:17] Support for The Real Pink Podcast comes from Menarini Stemline. No two breast cancers are the same, and researchers have come a long way in understanding what makes each breast tumor unique. That’s the entire premise behind personalized medicine. By looking at a tumor’s biomarkers, doctors can tailor their patient’s treatment to best fight their unique tumor.

[00:00:40] On today’s show, we’ll be discussing biomarkers that doctors look for in breast tumors and how they use them to design a treatment plan. We’ll also hear about a new twist on an old biomarker, the estrogen receptor, and how it’s being put into clinical practice. Joining us today on the show to share her experience is Dr.

[00:00:59] Virginia Kaklamani, MD, Dr. Kaklamani is a professor of medicine and leader of the breast cancer program at UTHealth San Antonio MD Anderson Cancer Center. Dr. Kaklamani, welcome to the show!

[00:01:15] Dr. Virginia Kaklamani: Thank you for having me.

[00:01:16] Adam Walker: Well, I’m, I really appreciate you taking the time to, to talk about this. It’s important. It’s it’s complex.

[00:01:23] So I’m looking forward to how you explain it all. So so we talk a lot about personalized medicine, but can you tell us what personalized medicine is first and then what it means for someone with breast cancer?

[00:01:35] Dr. Virginia Kaklamani: Yeah, so, so when we design our treatments, we designed them to work on all breast cancer patients, but we recognized very early on, not.

[00:01:44] that not all breast cancer patients are the same, not all breast cancers are the same. So when we talk about personalized medicine, we talk about the specific medicine that is the best medicine for that specific patient. And for that specific patient’s cancer. And this really has to do with biomarkers that we have when we look at cancers.

[00:02:06] And so we’re able with very molecular, very good molecular assays to tease out specific changes in that cancer. And thankfully now we have several drugs available for those specific changes.

[00:02:22] Adam Walker: Interesting. Interesting. Okay. So so when it comes to breast cancer, I know doctors use several biomarkers to identify which type or subtype someone’s cancer is.

[00:02:32] So can you tell us a little bit more about those biomarkers and what role they play in how doctors identify what treatments a person might receive?

[00:02:39] Dr. Virginia Kaklamani: Yes, so our kind of our more crude biomarkers that we look at are the estrogen receptor, progesterone receptor, and another receptor called HER2. And those are proteins on the cancers.

[00:02:52] And those tell us if we can use anti estrogen therapy for those cancers that feed off of our body’s estrogen. And also we can use some anti HER2 antibodies if the cancers have a lot of expression of this protein called HER2. But in the past several years, we’ve gotten to a point where we use a lot more detailed biomarkers.

[00:03:13] And that’s where we start looking at other changes. And one of those changes, for example, is mutations, changes in the estrogen receptor.

[00:03:23] That make this protein active and so even if we can take estrogens away, this protein still is active, it can still help those cancer cells grow. So then the thought was, well, let’s design better medicines that are able to attack this protein, even though it likes to be active.

[00:03:45] And block it in a better way than what we already had available.

[00:03:50] Adam Walker: Okay. Wow. And so, so as you mentioned, you know, one of the biomarkers that doctors look for when diagnosing someone’s cancer is the estrogen receptor. And I know that the main gene that creates the estrogen receptor is called the ESR1.

[00:04:05] So can you explain to us like what the ESR1 is and why it matters to doctors when they’re diagnosing and treating breast cancer?

[00:04:12] Dr. Virginia Kaklamani: Yeah, so I’ll take you back to your biology class of when you were in the 6th and 7th grade. I’m sure you love that.

[00:04:19] Adam Walker: It’s been a minute.

[00:04:22] Dr. Virginia Kaklamani: And so we start from the DNA and genes.

[00:04:24] Those genes become RNA and then that RNA becomes a protein. And the protein is what the cells understand as the language, the alphabet in a way. And so if that protein is a little changed, then the function changes, and then anything that happens in that cell or cancer cell changes. So, a lot of stuff may happen during that whole process, from the gene, to the RNA, to the protein.

[00:04:52] In this case, the gene, so the DNA, changes. And that change that is, that happens in that gene creates a protein, the ER, the estrogen receptor, that is abnormal. And it’s abnormal because it’s just active. And, you know, the cancer cells are very smart. They find ways. to adapt very quickly to whatever treatments we give them.

[00:05:19] So, initially, when we say, you know what, this is an estrogen positive breast cancer, and so, it uses estrogen as its food. And so, what’s the easiest way to attack it? Just get rid of the food. Take away the food, cancer dies. So, we took away the estrogen. And then the cancer cell said, well, hold on, I’m going to adapt and I’m going to use, I’m not going to use estrogen.

[00:05:41] I’m not going to need estrogen. I’m going to need different food. I’m going to make that estrogen receptor just active regardless of whether it has the food or

[00:05:50] not. And

[00:05:51] so that’s what happens with these ESR1 mutations. They just create a receptor that is active regardless of whether it has food or not.

[00:05:59] Adam Walker: Okay. Okay. And so, so I know some genetic mutations influence. Someone’s risk of developing breast cancer like the BRCA one or the BRCA two. What does it mean for a tumor to have a mutation in the ESR1 gene?

[00:06:14] Dr. Virginia Kaklamani: Yeah, so that’s a great distinction here. There’s some mutations that we are born with, mutations that are passed on from our.

[00:06:22] Fathers and mothers. And those are mutations that predispose us to getting cancer. And like you said, the BRCA1 and BRCA2 mutations. But then there’s other mutations that happen in the cancer itself. And those are in a way

adaptive mutations. Mutations that help the cancer adapt to the environment that it’s in.

[00:06:39] Because it’s just so smart. And so these ZSR1 mutations make that cancer Not need estrogen.

[00:06:48] Adam Walker: Okay, interesting. So where do these mutations come from and can you is there are the people like certain types of people that are most likely to have them.

[00:06:56] Dr. Virginia Kaklamani: So the cancers that are estrogen positive, where we have already treated them with anti estrogen therapies.

[00:07:03] Those are the ones that involve and adapt and create these ESR1 mutations. so that those estrogen therapies are not affecting them.

[00:07:12] Adam Walker: Oh, okay. And so, so what do doctors do to test for ESR1 mutations and how often should somebody be tested for that?

[00:07:20] Dr. Virginia Kaklamani: So it’s a simple blood test because what happens with cancers is they shed DNA and that DNA is shed into our bloodstream.

[00:07:28] And so if we do a blood test, we can detect the DNA from the cancer. And by detecting the DNA from the cancer, we look at that ESR1 part of the DNA, and we see if there’s a mutation. So, very simple blood test. We don’t typically do it when a patient is initially diagnosed with breast cancer, because as I mentioned, these are cancers that evolve, and so you want to do the test if a cancer spreads.

[00:07:50] And even if it spreads, if we keep giving it anti estrogen therapy, it’s likely at some point to develop an ESR1 condition. So you want to keep checking. So one test may not be accurate enough, but if you do detect it at some point, then you don’t have to keep checking.

[00:08:07] Adam Walker: So earlier this year, elacestrant became the first breast cancer medication approved specifically for people with advanced ER plus breast cancer with an ESR1 mutation.

[00:08:18] Can you explain why some patients with ESR1 mutations may benefit from a treatment that targets tumors with ESR1 mutations?

[00:08:26] Dr. Virginia Kaklamani: Yeah, so, so first of all, this was actually really cool because the last drug we had approved for anti estrogen therapy was more than 20 years ago. So for 20 years, we really had nothing new, and then all of a sudden a new drug.

[00:08:40] So, patients whose cancers have these ESR1 mutations, Are not and have already typically been on some anti estrogen therapy and that asked anti estrogen therapy doesn’t work and so then we have a couple of different options. First, is do we want to give them chemotherapy, which we always try to avoid or delay as much as we possibly can, or can we give them any more anti estrogen therapy and for that to work.

[00:09:06] in a cancer that has this ESR1 mutation, it has to be very strong. It has to be a mutation, a drug that bypasses what that mutation does to the receptor. And elacestrant is one of those drugs.

[00:09:19] Adam Walker: Oh, interesting. Okay. I appreciate you explaining that. So, so then last question what questions should patients ask their doctors when it comes to testing and monitoring their breast cancer and particularly For ESR1.

[00:09:34] Dr. Virginia Kaklamani: So it’s extremely important for patients to be well educated, for patients to be their own best advocates. We as healthcare providers know a lot, read all the time. We get tested all the time, but we are not machines and we’re not perfect. And machines are not perfect either because they don’t know the patients that we have in front of us.

[00:09:52] So this is really a team. And it’s not just a patient telling the physician what to do. And it’s not just a physician telling the patient what to do.

[00:10:00] This has to be a conversation. There has to be a lot of questions. And I can tell you, I learn from my patients all the time. They ask me certain things because they may have read it or heard it on TV.

[00:10:09] And I go, Oh, you know what? I think that’s a great idea. So in this case, it’s important that patients ask their doctors if they should have testing, because we’re not going to know if you’re eligible for a drug like Alicesterone, unless we test the cancer and we find an ESR1 mutation. So the first test is let’s do some testing, molecular testing.

[00:10:28] What is the, what are the characteristics of this cancer? And for ESR1 mutations, it’s important because they develop over time that you may want to test more than once. So even though you may have test the first time

that cancer has spread, you may want to test a second time after one of the treatments isn’t working anymore.

[00:10:46] And sometimes a third time when a second treatment is not working.

[00:10:51] Adam Walker: That’s great advice. That’s great advice. Wow. Well, this has been really helpful really insightful. I really appreciate you taking the time. Do you have any final thoughts you’d like to share with our listeners before we go today?

[00:11:02] Dr. Virginia Kaklamani: The advances that have been made in the field are just extraordinary. So the treatments that we now are using, we may be using many different treatments in a couple of years. So always ask your doctors what’s new, what clinical trials I might, maybe I’m eligible for, because that’s how we’re going to improve the field and eventually cure breast cancer.

[00:11:22] Adam Walker: That’s right. That’s very well said. Well, Doctor, I really appreciate you taking the time to be with us on the show today and hope you have a great rest of your day.

[00:11:30] Dr. Virginia Kaklamani: Thank you too.

[00:11:32] Adam Walker: And thanks to Menarini Stemline for supporting The Real Pink Podcast. You can learn more about ESR1 mutations in ER positive HER2 negative metastatic breast cancer at www.

[00:11:43] Menarini. com. Dot know esr1.com. That’s no KNOW ESR1.com.

[00:11:56] Thanks for listening to Real Pink, A weekly podcast by Susan G Komen. For more episodes, visit real pink.Komen.org. And for more on breast cancer, visit Komen.org. Make sure to check out at Susan G Komen on social media. I’m your host, Adam. You can find me on Twitter at AJ Walker or on my blog adam j walker.com.