Breast cancer researcher explains value of molecular analysis, gives overview of disease

Host Amber Smith: Upstate Medical University in Syracuse New York invites you to be "The Informed Patient" with the podcast that features experts from Central New York's only academic medical center. I'm your host, Amber Smith. Many questions remain to be answered about how and why breast cancer develops. Today I'm speaking with Dr. Kornelia Polyak about the research she's doing. Dr. Polyak was invited to come to Upstate to give the annual Baldwin Breast Cancer Research lecture. She's a professor at Harvard Medical School, and her lab at the Dana-Farber Cancer Institute is dedicated to the molecular analysis of human breast cancer. Welcome to The Informed Patient, Dr. Polyak.

Kornelia Polyak, MD, PhD: Thank you. And thank you for having me here.

Host Amber Smith: Your overall goal is to improve the clinical management of breast cancer patients. What are your priorities for improvement?

Kornelia Polyak, MD, PhD: Well, what we focus on, we and others, focusing on is to develop really individualized treatment plans for the patients. That includes studying the tumor, the specifics of the tumor, but we are realizing it's actually not just the tumor that is important for determining the course of the treatment for the whole patients. Many other factors, particularly the immune system, seems to have very important influence on how the patient will respond to treatment and what outcome they have. So really going into, like, understanding the patient as a whole and designing therapies based on that.

Host Amber Smith: Currently, how accurately can doctors predict cancer or its progression?

Kornelia Polyak, MD, PhD: It depends on the cancer. We have many molecular tests that you can run on the tumor to predict who's likely to respond to what kind of treatment. So breast cancer, for example, is not a single disease. We have like three major types. One is a hormone receptor positive, so those respond to hormone therapies. Then there is a so-called HER2-positive, which is driven by a gene that's called HER2, (a protein called human epidermal growth factor receptor 2.) And there are many targeted therapies against that particular oncogene that drives those tumors. And then you have the third type, which is called Triple Negative just because it's lacking the hormone receptors and HER2, and for that patient's chemotherapy with immunotherapy, which is a new, exciting development is what the usual standard of care. And each one of these have predictions of likelihood of progression, which very much is dependent on the stage of diagnosis. So, you know, the earlier you diagnose a cancer, you have a higher likelihood of successful treatment. Advanced stage cancers, unfortunately, are more difficult to treat. So that kind of determines what is your prognosis and what treatment would be the best for you to have the best outcome.

Host Amber Smith: Is there a scientific consensus on what causes breast cancer to metastasize or spread?

Kornelia Polyak, MD, PhD: It's not entirely clear. You know, some of the features of the tumor can make one tumor more likely to metastasize than others. For example, in breast cancer, the so-called triple negative -- which is the one that's lacking the hormone receptors and HER2 -- that's very likely to metastasize, unfortunately, and also metastasize to pretty much all of the organs in the body and even to the brain, which is one of the worst sites for a metastatic disease.

The hormone receptor positive one is less likely to metastasize and more preferentially forms metastasis to the bone. So in some way, the tumor type can determine the likelihood of metastasis and also the site of metastasis. And then we are starting to understand more and more about the role of the immune system, you know. For cancer cells to spread in your body, they have to evade the immune system because our immune system tries to eliminate cancer. But cancers figure out mechanisms that makes them able to overcome that. So, that's an area that's a very intense investigation, to figure out how we can reactivate the immune system and eliminate those disseminated cancer cells in the different parts of the body.

Host Amber Smith: Dr. Polyak, can you tell U.S. about your cancer heterogeneity studies?

Kornelia Polyak, MD, PhD: Yes. So we have been studying tumor evolution and heterogeneity. So tumors, heterogeneity means that cancers can be heterogeneous among different patients. So that's, we call that entire patient heterogeneity. But even in one patient, at one time, in one tumor, there are many kind of cancer cells.

So if you have even a small tumor, like a centimeter size tumor, which is considered fairly small, that's already like 10 to the millions of cancer cells, and they are not all the same. You know, they can be different properties, like different various expression of genes. Even if you think about the location of the cancer within a tumor, like a 1-centimeter tumor, whether it's closer to blood vessels or further away, that all creates heterogeneity because the environment where the cancer cells are selects for particular type of cancer cell that can survive there. So that's why it's so challenging to cure cancer.

And I like to use the analogy of: imagine you have a bucket, and the bucket is filled with different colored balls. Each one is a different color, but on top of that, imagine that those are those flashing balls, you know, they're flashing with a light, that they're changing colors. And then you're trying to treat the red ones, but then the red ones turn green, and that keeps happening over time in the tumor. And then, when they become metastatic, then the different colors can metastasize to different organs. And then they will, again, keep changing. And that's why it's been so challenging to very effectively treat cancer, especially the more advanced stage it is because then you have even many more different varieties of cancer cells. So even if you have like 1% of the cancer cells that don't respond to treatment, that's enough to regrow the tumor. And that's one of the challenges we have, and we and others have been studying. And we are trying to understand what drives this heterogeneity and also how we can come up with combination therapies to treat the heterogeneous tumors more effectively.

Host Amber Smith: This is Upstate's "The Informed Patient" podcast. I'm your host, Amber Smith. I'm talking with Dr. Kornelia Polyak. She's a professor at Harvard Medical School, and her lab at the Dana-Farber Cancer Institute focuses on the molecular analysis of human breast cancer. She was invited to Upstate to give the annual Baldwin Breast Cancer Research lecture.

I wanted to ask you about the lifespan of a breast cancer cell. Are you saying that these breast cancer cells change shape or size during their lifespan?

Kornelia Polyak, MD, PhD: Yes. It's not always the same cancer cell, but then they have a progeny like the cancer cell give rise to another cancer cell. Then when they divide, then those properties can change. And we think that most tumors actually take many years to develop, and some cancer cells can proliferate or give rise to many more progeny. And many times cancer goes undetected until it either you go for a screening or it becomes symptomatic. But usually by that time it's a reasonable size, meaning like, .5 to 1 centimeter size is usually what we can detect with the current technologies. But maybe it was already there for many years, and we just haven't been able to detect it. So, they can have many years of living or not necessarily always the same cell, but the progeny of the cells.

Host Amber Smith: How many times might a cancer cell divide in its lifespan? In other words, how many additional cancer cells might it create in its lifespan?

Kornelia Polyak, MD, PhD: That depends on the tumor, but in general, one of the features of cancer cells is that they have an uncontrolled cell division. So they divide many more times than normal cells would divide. And they also don't respond to the kind of inhibitory factors that would limit their ability to divide. So that's one of the feature of cancer, is the uncontrolled division. The actual number of divisions, it's hard to count, again, but it can, it's certainly many more than a normal cell would divide.

Host Amber Smith: Now, your lab is focused on identifying the differences between normal and cancerous breast tissue. Can you tell us what is known so far?

Kornelia Polyak, MD, PhD: Well, cancers generally have mutations, which means that there are some changes in the DNA that lead to some abnormal function. Normal cells obviously don't have that, so that's one of the very important features of cancers, that they have some genetic alterations which are inherited, and they basically have this very high degree of heterogeneity. And that enables the selection of cancers with different properties. And then, as I mentioned also, the cancers don't respond to normal controls to divide or not divide. They just take on and become much more independent. They are more likely to be able to spread and go to different parts of the body. And then I mentioned at the beginning that one of the important features of cancers is to evade the immune system, meaning like being able to shield themselves from the immune cell attack that normally would eliminate cancer. And the cancers that can grow have some way of overcoming these immune recognition and immune elimination that's very important for tumor growth.

Host Amber Smith: Considering the immune system's role or potential role in cancer, does that have any effect on whether you would recommend radiation or chemo for a patient who has breast cancer?

Kornelia Polyak, MD, PhD: So actually the immune system plays very important roles to respond to treatment. Even chemotherapy is much more effective in patients whose tumor has more immune cells because the immune cells are important to eliminate the cancer cells. So the chemotherapy induces killing of the cells, but then you need the immune cells to eliminate them. And similar with radiation. Radiation can cause an inflammation of the tissue, which can activate the immune cells. So the immune cells play an important role in treatment response, even when it's not an immunotherapy because radiation and chemotherapy activate the immune cells, in a way, and that's usually beneficial to help with more effective treatment.

Host Amber Smith: What can molecular analysis reveal about cancer? And can you give us some examples of how that information might be used in patient care?

Kornelia Polyak, MD, PhD: Breast cancer, again, is one of the best examples that based on the molecular analysis of the tumor. So every patient, when they are diagnosed with breast cancer, the pathologist will run a test to look at the estrogen receptor, the HER2 protein that I mentioned. That's very important to determine what treatment they get, because if you have the hormone receptors, then you are going to get endocrine therapy, hormonal therapy. If you have the HER2, then you get the HER2-targeted therapy.

And other cancer types, nowadays it's more routine that they are sequencing the mutations, like what are the genes that are abnormal in a cancer. And some cancers, there is a very specific targeted therapy based on the mutations they find. For example, in lung cancer, the people who develop lung cancer who are non-smokers very commonly have a mutation in a gene called EGFR, and there are very specific inhibitors for that gene. So that's how we are becoming more and more able to design the treatment specific for the tumor based on knowing the molecular features of that particular tumor. And that's true in breast and many other cancer types as well.

Host Amber Smith: If a woman has a mammogram, and the mammogram detects a suspicious lump, but then that lump is found to be benign and not cancerous, what assurances are there that that will not turn into cancer later? Or does a lump like that still need to be treated?

Kornelia Polyak, MD, PhD: Well, it depends on what type of a lump it is and what is the histology. They always do biopsy, and the biopsy will determine what is the definition, but if it's a benign fibroadenoma or even some other benign hyperplasias, those don't become cancer. But if you have such a lesion in your breast, that means that you are generally at higher risk of having the cancer. It doesn't mean that that particular lesion will become the cancer, but it's kind of a mark that you have some higher likelihood to develop cancer in some other part of the breast. So, fibroadenomas never become really breast cancer, but they do indicate that you may have higher risk.

Host Amber Smith: Well, Dr. Polyak, I really appreciate you making time for this interview. Thank you.

Thank you so much. My guest has been Dr. Kornelia Polyak, a professor at Harvard Medical School with a research lab at the Dana-Farber Cancer Institute. She's in Syracuse to give the annual Baldwin Breast Cancer Research lecture. "The Informed Patient" is a podcast covering health, science and medicine, brought to you by Upstate Medical University in Syracuse, New York, and produced by Jim Howe. Find our archive of previous episodes at Upstate.edu/Informed. This is your host, Amber Smith, thinking you for listening.