Dr. Samira Syed, MD, is an Associate Professor of Internal Medicine at UT Southwestern Simmons Comprehensive Cancer Center, where she treats patients and focuses on breast cancer research. In this interview, Dr. Syed discusses recent therapeutic advances and future directions in the treatment of patients with breast cancer.
This interview has been conducted in partnership with the National Breast Cancer Foundation (NBCF). Recognized as one of the leading breast cancer organizations in the world, NBCF is Helping Women Now® by providing early detection, education, and support services to those affected by breast cancer. A recipient of Charity Navigator's highest 4-star rating for 14 years, NBCF provides support through their National Mammography Program, Patient Navigation, breast health education, and patient support programs. For more information, please visit https://www.nationalbreastcancer.org/
Oncology Data Advisor: Welcome to Oncology Data Adviser. Thank you for being with us today, Dr. Syed.
Samira Syed, MD: Thank you for having me here today.
Oncology Data Advisor: To start off, what are some of the most challenging aspects of treating patients with breast cancer?
Dr. Syed: Well, I think that breast cancer, in some ways, is a very rewarding field, but also a difficult field. What I find most challenging is managing patients who have metastatic disease or advanced disease and balancing their treatments and the toxicities of those treatments with their quality of life and goals in life. A lot of times in that setting, we can't cure the patients of their cancer, so we have to kind of work with them in finding that balance. That probably is the most challenging part. But at the same time, we have a lot of new and exciting treatments, and many women do so well that it's, in many ways, rewarding also.
Oncology Data Advisor: What are some of the recent advances that have been made in breast cancer treatment?
Dr. Syed: Well, it's an exciting time, for sure. You know, every year we have several new drugs approved, and we've been very fortunate that way. There are a number of areas that particularly excite me, and I'm very hopeful for my patients. The first would be the application of immunotherapy in breast cancer. There's one subset of breast cancer, triple-negative breast cancer, that's highly aggressive. Outside of chemotherapy, for the longest time, there wasn't much other treatment. We now have, based on several studies both in the metastatic or advanced setting and in earlier stages of disease, drugs such as programmed death-ligand 1 (PD-L1) inhibitors. There's a drug called pembrolizumab that targets PD-L1, and it's an immunotherapy. Combined with chemotherapy, these drugs seem to really improve outcomes for our patients both before surgery in early breast cancer and, of course, in later stages of disease. The application of immunotherapy in breast cancer is very exciting, and it's still evolving to include other types of breast cancer besides triple-negative breast cancer.
Another area is the antibody-drug conjugates. These are drugs that have chemotherapy attached to an antibody, and in some ways, they're a targeted treatment. We have these for both human epidermal growth factor receptor 2 (HER2)–positive breast cancer, as well as for triple-negative breast cancer. For example, sacituzumab is an antibody-drug conjugate targeting Trop-2, and that is very effective in triple-negative breast cancer in the advanced setting. Then we have another drug called fam-trastuzumab deruxtecan that is very effective in HER2-positive breast cancer. We now have evidence from a recent study just presented a few weeks ago at the European Society for Medical Oncology (ESMO) meeting. That study was the DESTINY-Breast03 study, which compared this particular drug to another antibody-drug conjugate called T-DM1, and trastuzumab deruxtecan performed better. We're excited that we have more effective drugs of that nature that are more targeted in various different types of breast cancers.
So those are two of the really exciting areas. There are, of course, several other areas, but I think the movement is to move towards more precision medicine and more targeted treatment, and to try to decrease the side effects and the toxicity at the same time.
Oncology Data Advisor: Of the agents currently in development for breast cancer, which do you think are the most promising?
Dr. Syed: I think that we're beginning to understand that breast cancer is not one disease. There are many types of breast cancer, and they all need to be treated individually. We need to understand the biology. It's not so much the stage of cancer as it is the type of cancer and the genetic makeup of the cancer that should dictate future treatments. As I mentioned, we have several new antibody-drug conjugates that are under development targeting these different sites. For example, there's a drug called DS-1062, which is another Trop-2 inhibitor under development. There's another antibody-drug conjugate targeting HER2 called SYD985. These are both under development and look very promising. That's definitely an area of development.
Then the other area in hormone receptor-positive breast cancer is the development of drugs called serum estrogen receptor down-regulators (SERDs). We do have drugs in that category already available. These are given as an intramuscular injection and are usually used in the setting of metastatic disease to block the estrogen receptor and downregulate it. But what's exciting is we now have oral agents that are being developed with that same effect. These drugs are going to be very important in treating estrogen receptor–positive breast cancer, which is one of the most common types of breast cancer that we have. Again, these oral agents will allow patients to not have to come into the clinic and be on shots; they'll just be kind of being treated at home. We're very excited about these drugs.
Then a small percentage of patients do have genetically predisposed breast cancer, and they have mutations such as the BRCA1 and the BRCA2 genes. These are genes that make individuals very prone to breast cancer. However, we now can target those genes, and we have very effective therapies that exist to do that. There is a class of drugs called poly–adenosine diphosphate ribose polymerase (PARP) inhibitors that are effective in these patients. We have newer PARP inhibitors under development that are more effective, and maybe less toxic, that are being applied in both early breast cancer and later breast cancer. We're excited that even patients who have a genetic predisposition, who have these mutations and are very prone to breast cancer, have these newer options that are targeted. I think there are a lot of exciting developments and a lot of newer medicines that are coming out, hopefully in the next year or two, that will enhance our toolbox to treat these patients.
Oncology Data Advisor: How do you foresee the treatment of breast cancer continuing to evolve in the coming years?
Dr. Syed: I think that one of the challenges in breast cancer and in cancer in general is that some of our treatments are very toxic. When we started this journey, we kind of treated all cancers, and particularly all breast cancers, the same. We now know that there are many different types of disease, and we are also beginning to scale back on certain treatments in certain populations. For example, in the setting of estrogen receptor–positive breast cancer, we can use genomic assays to understand who needs chemotherapy and who doesn't in early breast cancer. That is a de-escalation strategy. In the same way, by using some of these targeted therapies, they're able to de-escalate treatment in individuals who don't necessarily need the very strong or toxic regimen.
What's exciting, and what I think will be the way forward, is de-escalating and treating different patients differently, depending on what their risk is and depending on what their cancer type is. I think that's definitely going to be a way forward. That will actually also be applied to surgical treatment for breast cancer, where they're doing less invasive and less aggressive surgeries, and then also in the setting of chemotherapy and other systemic therapies, where we're trying to scale back when we can. In doing so, we can prevent a lot of the side effects and the toxicities that patients have to go through.
So definitely the future direction will be more towards precision medicine and de-escalation, where appropriate. I think that's going to be our way forward, and it's exciting because our patients deal with so much when they go through these treatments, with some of the side effects that can last for a very long time. It's nice to be able to advise patients of their risk and then tell them that maybe they don't need everything that another person needs because their cancer is less aggressive. We determine that by these molecular tests.
About Dr. Syed
Samira Syed, MD, is an Associate Professor of Internal Medicine at UT Southwestern Simmons Comprehensive Cancer Center, where she sees patients in the Division of Hematology-Oncology, with a clinical focus on breast cancer. Her research interests include gastrointestinal malignancy, drug development in cancer, and treatment and management of breast cancer.
For More Information
Cortés J, Kim S, Chung W, et al (2021). Trastuzumab deruxtecan (T-DXd) vs trastuzumab emtansine (T-DM1) in patients (Pts) with HER2+ metastatic breast cancer (mBC): results of the randomized phase III DESTINY-Breast 03 study. Ann Oncol (ESMO Virtual Congress Abstracts), 32(suppl_5):S1283-S1346. Abstract LBA1. DOI:10.1016/annonc/annonc741
Transcript edited for clarity. Any views expressed above are the speaker's own and do not necessarily reflect those of Oncology Data Advisor.