Advances in Breast Cancer Treatment
At the 2018 American Association for Cancer Annual Meeting, Dr. Osborne was honored with the 2018 AACR Distinguished Award for Extraordinary Scientific Achievement and Leadership in Breast Cancer Research, in part for his stewardship of the San Antonio Symposium.
Listen to the podcast to hear Dr. Osborne discuss:
how our understanding of breast cancer has changed since the 1970s
the most promising areas of breast cancer research going on right now
the feasibility of a cure for breast cancer
Dr. C. Kent Osborne is director of the Dan L Duncan Comprehensive Cancer Center at Baylor College of Medicine, where he is also a professor and the Dudley and Tina Sharp Chair for Cancer Research. Since 1992, he has been a codirector of the San Antonio Breast Cancer Symposium, the world's largest conference focusing entirely on breast cancer. His own research focuses on improving the effectiveness of hormonal therapy medicines and targeted therapies that treat HER2-positive disease.
— Last updated on July 31, 2022, 10:20 PM
This content made possible by Lilly Oncology.
This podcast is made possible by the generous support of Lilly Oncology.
Jamie DePolo: Hello, everyone. I’m Jamie DePolo, senior editor at Breastcancer.org. We’re podcasting on location at the 2018 American Association for Cancer Research Annual Meeting in Chicago. My guest is Dr. C. Kent Osborne, who serves as director of the Dan L Duncan Comprehensive Cancer Center at Baylor College of Medicine, where he is also a professor, and the Dudley and Tina Sharp Chair for Cancer Research. Since 1992, he has been a codirector of the San Antonio Breast Cancer Symposium, the world's largest conference focusing entirely on breast cancer. His research focuses on improving the effectiveness of hormonal therapy medicines and targeted therapies that treat HER2-positive disease, and he has been honored with numerous awards for his research contributions to breast cancer treatment.
Dr. Osborne, welcome to the podcast.
C. Kent Osborne: Thank you very much.
Jamie DePolo: So, you started practicing in the 1970s…
C. Kent Osborne: Yes.
Jamie DePolo: So, a few years ago. How has our understanding of breast cancer, as well as treatments for breast cancer, changed since that time?
C. Kent Osborne: Well, I think it’s changed dramatically since that time. We knew very little about the biology of the disease back then. We were just learning about the estrogen receptor and what it did to regulate breast cancer growth and how to inhibit it. And the treatment at the time was everybody got the same treatment -- and that was a radical mastectomy, sometimes with also a chest wall radiation, and then, outside of a clinical trial, no other therapies after that. Adjuvant therapy was just being studied, so it wasn’t routine, and treatment for metastatic breast cancer was also very primitive with single agent drugs like Cytoxan or 5-FU, or methotrexate. So, compared to today, things were really primitive, and today it’s much, much different than when I first practiced.
Jamie DePolo: And it sounds like, today, things are much more targeted or specific. We know so much more about the biology of the disease.
C. Kent Osborne: Yeah. That’s true, and I think that’s led to what’s called now precision medicine, and that is taking into account the characteristics of the patient and their cancer and individualizing therapy. We’re now able to do that to a greater extent than we were back in the 70s, for sure.
Jamie DePolo: Which of the changes that you’ve seen has had the biggest impact, in your opinion?
C. Kent Osborne: Yeah, I think there’s a couple of them. One of them was the change in our concept about how breast cancer spreads. And for decades, since Halsted back in the late 1890s hypothesized that breast cancer spread in a centrifugal way, always connected to the primary, and that there was no such thing as a blood-born metastasis. And that hypothesis, which, when you looked at the data that came out of the original radical mastectomy studies, it didn’t hold water because most patients still recurred and died of the disease, despite the development of the radical mastectomy.
So, the change happened in the 70s largely with people like Bernie Fisher and others saying that the reason people were recurring and dying was not related to the extent of your surgery of the breast, but to the presence of micro-metastases that were already present by the time the diagnosis was made. So, that led to two ideas: One is lesser surgery -- you don’t need to do a radical mastectomy if your survival is dependent on having metastases in other parts of the body that are not treated by surgery, all right? And then, to give some sort of systematic therapy in addition to surgery to kill those seeds of cancer that were lying and you couldn’t find them by any test, but we knew they were there in a lot of patients.
So, that was one of the biggest changes, was the change that lesser surgery and systemic therapy to get into the bloodstream to kill those metastases. So, I would list that as a major change -- a conceptual change -- that led to different therapies. It might surprise people to understand what I think might be the best, the most important, change in metastatic disease might be the introduction of bisphosphonates -- not even standard treatment for the cancer. And the reason is, I can remember back 30 and 40 years ago always having several patients in the hospital suffering from bone pain, multiple fractures, and so forth, and their quality of life has been so much dramatically improved by bisphosphonates and now RANK ligand inhibitors.
We haven’t cured metastatic breast cancer yet, but we are doing better treatments. But, in terms of quality of life, bisphosphonates really dramatically changed that. We don’t see cord compression anymore. We don’t see bone pain anymore to the extent that we did before, so it’s made a dramatic improvement in the outcome of those patients.
Jamie DePolo: So you -- we’re at this meeting -- what are the most exciting or promising areas of breast cancer research that are going on right now?
Dr. C. Kent Osborne: Yeah. I think it falls into a couple of different areas. One would be, can we see the same favorable responses to immunotherapy or immune-oncology that we’ve seen in some other tumors? And that remains to be seen. We just don’t know yet. There’s some provocative early data that some patients may benefit, but studies are just ongoing, and we just don’t know yet who and how well they will benefit from immunotherapy. But it’s something that’s a major area of study. Everybody’s doing it right now. Another would be to continue our efforts to identify what are called driver pathways in a person’s tumor.
Jamie DePolo: And what is that?
C. Kent Osborne: It’s identifying which survival pathway in the cell is responsible for causing that tumor to grow. If you think of it this way: Every cell in our body, normal cell or a cancer cell, has several -- probably six or seven -- different pathways that keep it alive under various stressors. Cancer takes over one of those pathways, amplifies it, and makes it more active, and then you get cancer. Now, the problem is we had hoped that we would find evidence of which pathways were important by looking at the mutations in tumors, and that’s helped a little bit, but not so much in breast cancer as it has in other cancers. But what we did find is that there are hundreds of these mutations, or thousands of these alterations, in DNA in every person’s tumor. So now, trying to figure out which of those mutations is critical for the tumor growth so that we can block it, that’s one of the important things right now.
I think one of the ways to do that is to couple the DNA alterations with proteins that are expressed as a result of those mutations. Some of those mutations are innocuous -- they don’t do anything to the tumor -- whereas other ones are stimulating a protein that will cause a tumor to grow. So, this is sort of a new area, called proteogenomics, to try to figure out which is the driver pathway in your tumor versus my tumor, so that we can target it appropriately. So, I would say that’s another area of importance.
And then, lastly, we have pretty good treatments for breast cancer now. Some of them work and are curative, but many patients acquire resistance. They either have the resistance to the drug at the beginning, or the tumor responds for a while and then the patient acquires resistance down the line, years later. And understanding the mechanisms by which a tumor outsmarts us and outsmarts the drug and becomes resistant is another key area of research. Because if we can figure those out, then we could use those therapies to block those escape pathways earlier in the course and prevent that resistance from developing.
Jamie DePolo: At this AACR meeting, you are being honored with the 2018 AACR Distinguished Award for Extraordinary Scientific Achievement and Leadership in Breast Cancer Research. Congratulations.
C. Kent Osborne: Thank you.
Jamie DePolo: And this is, in part, for your stewardship of the San Antonio Breast Cancer Symposium. So, for our listeners, can you briefly explain why conferences like this meeting here and the San Antonio Symposium are so important for advancing breast cancer treatment?
C. Kent Osborne: Well, this is how we educate other physicians and scientists about what we’re doing. Rather than having to wait until you see the publication, you can see it firsthand here. And it’s just a form of distributing the message so that two people aren’t studying exactly the same thing or duplicating what somebody else already did. So, it’s a way of educating other scientists and essentially the public, as well. We’ve done a bad job, I think, through the years of educating the public about what science is accomplishing and what we’re doing. So, this is another way, through vehicles like yours, to help educate the public about how science works and what the accomplishments are and how we’re putting the puzzle together. It ultimately should lead to a cure in most cancers.
Jamie DePolo: Now, speaking of a cure, we’ve talked a lot about treatments. How about a cure? I mean, do you think that is feasible for breast cancer? Are we closer?
C. Kent Osborne: Well, I think we are curing a number of patients now. HER2-positive breast cancer, which used to be one of the more aggressive forms of the disease, I think is now highly curable with the new treatments that we have. So, we are curing a lot of patients with breast cancer by their surgery, and then adjuvant therapy with either endocrine therapy -- that is therapy to block estrogen for an estrogen-receptor-positive tumor -- or HER2-targeted therapy, for that subset of tumors, and chemotherapy for the ER-negative and HER2-negative tumors. But where we’re failing is in metastatic breast cancer, and it’s one of the mysteries to me, is why can we cure a patient where we may have microscopic seeds in their bone or liver -- microscopic metastases elsewhere in the body -- but if they have a tumor that measures one centimeter in size in the liver, we can’t cure it?
Why is that? What’s different? And there’s a lot of potential reasons, but, by that time, maybe there are already too many mutations and the tumor is more aggressive. Or, when you have a breast cancer that’s growing in the breast, it’s familiar -- it’s a familiar site, right, because it’s where normal breast tissue grows -- and a breast cancer that develops in the breast we can easily eradicate that very frequently now, with our treatment given before surgery.
Maybe when it gets into another site, and it travels to a distant organ, just the unfamiliarity of the cells in that tissue creates stresses on the cell, and then the cell activates multiple survival pathways to keep it alive. And there, as I mentioned earlier, there are multiple pathways that a cell can call upon to survive under various stresses. Maybe in the breast it’s calling on just one or two of those, but when you get to a metastatic deposit, it’s calling on multiple survival pathways, making it more difficult to kill with our standard treatments. So, that’s the big dilemma, and we haven’t been able to cure metastatic disease. It’s a major focus of our research now, I think.
Jamie DePolo: Okay. Thank you very much. I appreciate your time.
C. Kent Osborne: You’re welcome.