How Biomarkers, Genetics, and Genomics Help Guide Breast Cancer Treatment

[00:00:00] Adam Walker: Bayer is a Global Life Sciences leader in healthcare and nutrition. Building on a 150 year legacy in healthcare, Bayer is committed to improving patient lives by developing innovative therapies and delivering first-in-class educational and support programs to meet their needs.

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.

Today we are going to talk about biomarkers, genetics, genomics, and how they can assist both doctors and patients in determining the best course of treatment. Here today to help us understand the basics and complexities associated with biomarkers and genetics is Dr. Payal Shah.

Dr. Shah is a medical oncologist and clinical researcher who studies triple-negative breast cancer and cancer genetics at the University of Pennsylvania. She is the recipient of a Komen Career Catalyst grant. Dr. Shah, welcome to the show!

[00:01:06] Dr. Payal Shah: Thank you so much. Thanks for having me.

[00:01:08] Adam Walker: I’m excited to talk to you. This is complex so I know you’re going to break it down for us. So let’s dive in. Let’s see. Before we get into biomarkers and genes, let’s start with some basics. Can you tell us some of the tests that a person who’s been diagnosed with breast cancer might receive that will tell the doctor more about their tumor?

[00:01:28] Dr. Payal Shah: So, so this is a really good question, because I think understanding the basics of breast cancer really lays the groundwork for the rest of the discussion that a patient has with their doctor. So first there’s the stage of a tumor. So when we talk about tumor stage, we’re most often talking about how extensive is the cancer.

So there’s three pieces of that. We use something that we call the TNM system. T stands for tumor size. How big is the tumor. N stands for lymph nodes. So is it is a tumor that’s in the breast going into the lymph nodes? And if so, how many lymph nodes are involved? And then the letter M stands for metastasis, which means is their spread of the cancer outside of the direct area of the breast and the lymph nodes?

And then, so that TNM system then translates into different stages. So there stages zero through four. Stage zero is what we call ductal carcinoma in situ and it’s basically breast cancer that’s in there, but there’s no ability for that cancer spread or invade. And then stage four cancer is cancer that does have spread to a different part of someone’s body. And then stages one and three are basically between those stages zero and four.

So there’s also some more specific ways to describe a breast cancer based on additional tests that a pathologist does on the tumor sample. So this is when someone has their surgery, that surgery gets put taken to a lab where a pathologist looks at it under a microscope.

They usually categorize its general appearance. So sometimes they’ll say words like ductal or lobular or metaplastic and that’s like the general category of breast cancer. They also talk about grade, which is how abnormal do the cells look under the microscope? And a higher grade basically means more abnormal, a lower grade means the cells look there’s still cancer, but they look a little bit less abnormal.

And then, for breast cancer, there’s also three specific additional tests that any pathologist will do. One is they check for something called the estrogen receptor. A second test that they do is called the progesterone receptor. And a third thing they look at is a protein called HER2. And so estrogen and progesterone are hormones that some cancers use as food to grow.

And so testing whether or not, or how much expression of those proteins thE cancer has tells us about whether or not that tumors using hormones as food to grow. And same thing with the, HER2 protein is that a driver of breast cancer. So those are the general features that someone should know about their cancer when they’re first diagnosed.

[00:04:12] Adam Walker: Okay. So that’s a lot. That’s a lot of testing, a lot of work. I did not expect there to be that much going like upfront. So that’s a lot up front. I assume it gives doctors and patients a lot of information. And you mentioned biomarkers as something that could be identified to help guide treatment.

What is a biomarker and what do they mean for people related to breast cancer?

[00:04:35] Dr. Payal Shah: So definitely. So biomarker is something that we measure or test for. So it can be something in someone’s blood, in their tumors, somewhere else in their body. And it’s really, it’s a general word of something that we test for that indicates disease and often indicates whether or not treatment is going to work or not work in a particular tumor.

For example, I mentioned the estrogen receptor. That’s a biomarker of treatment response to anti-estrogen therapies. BRCA one and two are genes that sometimes if certain mutations can lead to an increased risk of developing cancer, and those also can be biomarkers of treatment response to a category of drugs called PARP inhibitors.

 That’s that’s what biomarkers refers to. And I think genetic testing and genomic profiling are being looked at more and more as potential biomarkers.

[00:05:34] Adam Walker: And so so you’ve mentioned they’re being looked at more and more. I assume they’re being looked at by doctors because it would be meaningless to the rest of us. And so how are those tests and those biomarkers used to guide treatment for breast cancer?

[00:05:49] Dr. Payal Shah: Yeah it’s such a good question. So I think first we were talking about how important the basics are. I think I think genetic testing is a point of confusion.

So I’m going to take a minute to just explain what we’re talking about. So there is genetic testing that basically reveals what a person is born with, what they have inherited from their biological mom or dad. And that’s often tested for by looking at a person’s saliva or their blood. So you’ll hear sometimes you might hear your doctor talking about what we call germline testing.

That’s genetic testing that looks to see what one inherited, or what one has been born with. There’s also tumor testing as well. This is sometimes lumped into still like genetic or genomic testing, but now we’re not talking about what a person was born with. We’re talking about what’s going on in the tumor. And this is what we, you might hear your doctor use the word somatic testing. So this

is often done on like a, on a tumor biopsy. Although now we’re starting to do liquid biopsies as well, which are blood tests. But they still tell us about the tumor. So there’s basically the kind of two overarching categories, there’s germline or germline genetic testing which tells us about what someone is born with.

And then there’s somatic testing that kind of gives us insight into what’s going on in the tumor. Those can be used and are being used more and more to tell us about treatment. For example, PARP inhibitors are a category of drugs that have really done really well in patients who have inherited mutations in genes, such as BRCA one and two.

 There are also drugs that kind of targets specific somatic or tumor based genetic drivers. For example, I mentioned the HER2 gene earlier. I’m sorry, the HER2 protein. And when there are cancers that express too much of that protein, they can be really effectively targeted with medications like Trastuzumab or Pertuzumab.

 Another biomarker or tumor driver that we’re learning more about is involves the NTRK gene fusions. Which if those are present in a tumor can tell us a little bit more about using a couple of targeted therapies to help treat tumors that do have that gene kind of fusion or signature.

 That’s an overview of genetics and genomics and how that can influence treatment.

[00:08:26] Adam Walker: Okay, and so you mentioned the BRCA one and two mutations. That’s what’s often thought of related to breast cancer. Are there any other genetic mutations that might be identified through genomic testing?

[00:08:38] Dr. Payal Shah: Oh, absolutely. So I would say in the last decade or so, we’ve really learned about so many other genes that have specific mutations that can be linked to a higher cancer risk. So just to throw out a few there’s, there are genes called PALB2, aTM, Chek2, and others. And there are certain mutations in these genes that can be linked to higher risks of cancer.

But I do want to make a distinction. So these are genes that we all have a copy of. It’s not a bad thing to have the gene, we’re all born with the gene. It’s just, if you have a certain mutation or misspelling within the gene not all of those mutations cause problems, but some of them do. Those that are those that do, are what we call pathogenic or likely pathogenic. And those mutations within these genes can predispose to developing a higher risk of cancer.

[00:09:29] Adam Walker: Okay. That’s a good differentiator there. I appreciate you, I appreciate you explaining that. And so I’m just curious speaking of biomarkers, is there any research being done around biomarkers or driver mutations that can help personalize medicine to improve patient outcomes?

[00:09:47] Dr. Payal Shah: Oh, absolutely. There is so much. That’s basically the whole goal of precision medicine at this point. So I think we’re developing more and more technologies and more and more capabilities of understanding tumors and what their genetic drivers are, what proteins are overexpressed, and that’s really impacting treatment.

And the whole goal of all of this work is to figure out how can we develop treatments that are more effective and improve outcomes. And then also just as important, how can we develop treatments that are less toxic and allow people live with a good quality of life?

So that’s, there’s a lot of that work going on all over the country, all over the world, really. And yeah, that’s definitely an important goal.

[00:10:33] Adam Walker: I think you called it precision medicine. Is that right?

[00:10:36] Dr. Payal Shah: Yeah.

[00:10:37] Adam Walker: Okay. Okay. So I guess that’s ultimately kind of the goal of all this is being able to just customize treatment to the individual based on their own?

[00:10:45] Dr. Payal Shah: Absolutely. Yeah. On their type of cancer. That’s exactly. What on their type of cancer. And then also taking into consideration, not just the cancer, but the person and what, how old the person is, what is important to them.

 For example, if we have patients who are, I have a lot of young patients, some of them are dancers or artists by profession, I’m going to try to avoid drugs that give them neuropathy, which is numbness or tingling of the fingers that might make it hard for them to do what they love most. So I think the whole goal of precision medicine is to get to what’s really driving a tumor and hit that without hitting other things that might compromise a person’s quality of life.

[00:11:28] Adam Walker: Gotcha. Wow. That’s amazing. That sounds like just such amazing, such important work. Really appreciate you joining us on the show to share that.

Do you have any final thoughts you’d like to share with the audience?

[00:11:38] Dr. Payal Shah: No, I think I think you’ve really done a nice job of hitting some of the really big picture things with cancer and biomarkers. So thank you for having me

[00:11:46] Adam Walker: Well, Dr. Shah, thank you for all the work you’re doing. Thank you for joining us on the show, breaking down that incredibly complex subject.

And if any of our listeners want any more information on genetic, genomic, or tumor profiling tests, please look in the show notes for this episode for more educational resources. Dr. Shah, thank you again for joining us on the show today.

[00:12:06] Dr. Payal Shah: Thank you.

[00:12:10] Adam Walker: Genomic cancer testing, commonly referred to as biomarker testing, is used to identify unique DNA alterations or changes within cancer cells that determine how your tumor behaves and why it grows. That knowledge may help your doctor recommend treatments that have been approved or are in clinical trials based on your specific alteration identified. To learn more, visit testyourcancer.com.

Thanks for listening to Real Pink, a weekly podcast by Susan G Komen. For more episodes, visit RealPink.com. 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 @AJWalker or on my blog, AdamJWalker.com.