Phyllis Pittman, Founder and CEO of CMedEd, interviews Dr. Naoto Ueno, MD, PhD, FACP, Director of the University of Hawai‘i Cancer Center, at the start of Breast Cancer Awareness Month to discuss the latest news in breast cancer treatment.
Dr. Ueno has a strong background in translational breast cancer research in cancer biology, immuno-oncology, and molecular therapeutics. He is one of the leaders in conducting clinical research and early-phase clinical trials related to aggressive breast cancer and has led more than 50 clinical trials. Dr. Ueno has extensive experience in conducting both targeted therapy-related and immunotherapy-related clinical trials in phase I and II settings.
Phyllis: Let me introduce you to our audience today. Dr. Naoto Ueno is director of the University of Hawaii Cancer Center and professor of medicine, an internationally recognized breast medical oncologist and researcher. He joined the University of Hawaii in 2022 after more than two decades at MD Anderson Cancer Center where he led the world's largest inflammatory breast cancer program. At the University of Hawaii, he leads the only NCI designated cancer center in the Pacific, driving research, clinical care, and education with a focus on reducing cancer health disparities.
An NCI designation is the gold standard for cancer programs. It recognizes the nation's top centers for their innovative research and advanced treatments. His research explores tumor micro environment, rare and aggressive breast cancers and novel antibody drug conjugates. A dedicated educator and mentor, Dr. Ueno is also a TEDx speaker, author of two patient centered books, and recipient of multiple national teaching and membership awards. A two-time cancer survivor, he brings a unique physician, scientist, and patient perspective to his mission of equitable, compassionate cancer care.
So, Dr. Ueno, it's so nice that you're doing this, and I appreciate your time. It's breast cancer awareness month October and I know that what you're going to offer cancer patients and breast cancer survivors is of the utmost importance. The first thing I want to ask you is could you share what inspired you to dedicate your career to breast cancer research and patient care?
Dr. Ueno: I think it started from meeting Dr. Horovbaji and many other well established breast medical oncologists when I was training at MD Anderson which is almost three or four decades ago. I've seen physicians engage with not just clinical practice but also with clinical trials and basic research. Trying to translate the knowledge into clinic inspired me to become a physician scientist. I wasn't particularly exposed to breast cancer prior to this, but the people who I met triggered me to go into this field.
Phyllis: Thank you. You mentioned that you gave a TED talk. Could you tell our audience what the main point you were communicating concerning breast cancer in your TED talk?
Dr. Ueno: The TED talk is about patient empowerment. It applies not only to breast but other cancers, and you have to really take control of your journey, which is having the right knowledge. We talk like you're on the map and you need to know where you're standing in the journey of cancer, but you also need to know which direction it is. A lot of people think the physicians or their health care provider is a determining factor, but that's not true. We are supposed to be equal partners. Patient and health care provider are equal partners. That's probably the main topic.
Phyllis: I've known you for a number of years, and we worked together on many projects and inflammatory breast cancer while you were at MD Anderson. I have witnessed your compassionate patient care as well as your mentorship of medical students, graduate students and clinical trainees at MD Anderson. I remember my friend Sarah who had been misdiagnosed at another cancer institute and came to MD Anderson. You were her main provider and her care doctor, and you were so understanding to both she and her mother. You were always available and made sure that she received the very best care. Your compassion felt so genuine and heartfelt. Does that come naturally to you or is it something you've learned along the way as you're taking care of patients?
Dr. Ueno: I would say it's a process. You see people struggling through their process and patients as well as my mentors and colleagues really impact how you provide the care. Medicine is about team approach. The funny part is that this team approach we talk about a lot, but we don't teach in medical school or even during residency what is team. Team is really sometimes driven by knowledge, but I think MD Anderson particularly emphasizes not just knowledge but your interaction with your colleagues and your patients. So I think it's the process that brought me to where I am.
Phyllis: You are exceptional on so many different levels. I've been involved in patient education for a number of years and we started CMedEd, and you've been such a major contributor to our website with information on breast cancer and I thank you so much for that.
Dr. Ueno: You're welcome. We believe that the more a patient knows the better the outcome is going to be. Knowledge is power—power to ask questions, come to a decision about treatment and the future, and have a greater understanding. A relationship with your oncologist is so important. You need a map of what the treatment is going to look like, the side effects, what dos and don’ts you can do, and how you can participate in life and go forward—vacations with children and grandchildren. It’s very important.
Phyllis: You're such a knowledgeable scientist and researcher. I wanted you to talk about some exciting developments in what you're doing for breast cancer right now and explain the benefits of an antibody drug conjugate and how it works.
Dr. Ueno: Antibody drug conjugate is chemotherapy but targeted chemotherapy. The way it works is you have the chemotherapy and then the antibody, which is a biological agent that binds the cancer specifically. So there are two components, and something chemically links them together. That's why it's called antibody drug conjugate. ADC allows very toxic items to be delivered to the cancer more specifically and that's why it's very effective. At this moment we have two drugs—technically three—but the recent two out of three are extremely effective.
Phyllis: Have these been approved by the FDA and are they being used with patients right now?
Dr. Ueno: Yes. They've been approved for probably five to seven years. They started with advanced disease, but both drugs are moving to the front—first line metastatic disease—and also into early disease. This is not FDA approved as an indication, but it’s well established in terms of efficacy and treatment. They want to deliver this drug in an early setting as much as possible.
Phyllis: There are so many advances that have been made for treatment other than chemotherapy. The next one we talked about was immunotherapy. This has transformed treatment in several areas. Can you explain its current role in breast cancer and where you see it headed in the future?
Dr. Ueno: The immunotherapy was first approved for triple negative breast cancer. Triple negative means estrogen receptor, progesterone receptor, and HER2 target are not noted. In triple negative metastatic disease, combining immunotherapy with chemotherapy has been effective. From there they moved it to early disease—newly diagnosed breast cancer without metastatic disease—and in that setting, chemotherapy effectiveness goes up and patients live better. That's the area currently FDA approved. Now the direction, also not yet FDA approved, is to combine immunotherapy with ADCs. That combination is showing promising outcomes and I believe those will eventually be FDA approved. Another area may be whether you could give immunotherapy in hormone receptor or estrogen receptor positive disease. That may be another area we’ll see in the near future.
Phyllis: That is so exciting to hear—the antibody conjugate and the immunotherapy. Women and men diagnosed with breast cancer are often concerned with the side effects. Immunotherapy in breast cancer harnesses the patient's own immune system to target and destroy the cancer cells. So it's not systemic, meaning that it does not go through your whole system. Am I correct in saying that?
Dr. Ueno: That's true, as you said, Phyllis. Both of them are intended to be as specific as possible to the cancer, but in reality there's not a single drug without side effects. Maybe that’s the future we aim for and where research is going. There are side effects in both. Immunotherapy in particular, because you're manipulating your own body's immune system to fight the cancer, is a very delicate situation.
Phyllis: Interesting. Now, you're investigating tumor micro involvement and how it influences the way a doctor treats aggressive breast cancers like triple negative and inflammatory. You are one of the most renowned experts on both of these, in my opinion. Can you please explain tumor micro involvement?
Dr. Ueno: Tumor micro environment means there's a cancer and the surrounding of the cancer. A lot of people think we need to treat the cancer, but the reality is the cancer and the surrounding have an interaction that amplifies aggressiveness. There are lots of immune cells and normal cells. What we know is if we really want to get the best outcome, we need to control both cancer and the surrounding environment, which is the tumor micro environment. One example is immunotherapy—it’s not simply targeting the cancer, it’s targeting the surrounding of the cancer. We think there are more drugs beyond the current Keytruda, pembrolizumab, which is FDA approved and currently the only drug for breast cancer immunotherapy. But there are many components and many ways these things interact. We think there will be different types of immunotherapy or drugs that modulate or change the tumor micro environment coming in the near future.
Phyllis: Thank you for correcting me on microtumor environment, not involvement. The future of medicine is so exciting. You and so many of your colleagues have come so far in discovering new treatment methods and it's encouraging to all of us who have had family members or are cancer survivors ourselves like you. How long does it take for your discoveries from the lab to make their way to being offered to a patient?
Dr. Ueno: Historically, it’s been very long—two decades or so, with an average of about ten years. Recently, discovery to FDA approval for some drugs has gone to less than five years. There is an accelerated process happening due to better technology, smarter people, and the government approval process. Accelerated means approval with not completely mature data. A few drugs have been pulled off the market because they didn't have sufficient outcomes or side effects. It's complicated. We get excited by shrinkage of the tumor, and generally shrinkage is a reason to say a drug is good, but what we believe as clinical investigators is not just shrinking the tumor, but living longer. If you don’t live longer, shrinking the tumor doesn’t really matter.
Phyllis: Of course, longevity of life. Dr. Richard Pastor was at MD Anderson prior. He was a colleague of yours, a friend of mine, a friend of yours. He has made great milestones at the FDA in getting drugs approved to help people. He’s a medical oncologist himself. We’re so happy—he’s done a wonderful job there. I'm now going to switch.
Dr. Ueno: By the way, Dr. Pastor was my fellowship director.
Phyllis: Wow.
Dr. Ueno: He’s the one who interviewed me, and he’s the one who—I don’t know if he made the final decision—but I got into fellowship at MD Anderson.
Phyllis: I'm sure you had your own talents and attributes to get into MD Anderson. You're one of the most brilliant medical oncologists and compassionate doctors I've ever met. I want to switch over now to the University of Hawaii Cancer Center. It's unique because it's the only NCI designated cancer center in the Pacific. Becoming one involves rigorous standards—it’s the gold standard for cancer programs, bestowed upon the nation's top centers in recognition of innovative research and leading-edge treatments. How will you work to address the health disparities in Hawaii and the U.S.-affiliated Pacific Islands? That must be very challenging.
Dr. Ueno: It's a challenge and has been for many years. One of the biggest challenges we have is geographic isolation and the vast area that we cover. Hawaii itself is not contiguous—you can’t drive to the next town. We have many islands in Hawaii, but we also cover the entire Pacific, from west of Hawaii—Guam, American Samoa, Marshall Islands, and so on—about 2 million people. Geographic isolation, poverty, and race-based outcome differences are all factors. Native Hawaiian and Pacific Islander populations compared to White or Far East Asian have much higher cancer death rates. We emphasize education and prevention. We have one of the largest datasets related to what we call multiethnic cohorts—Native Hawaiian, Pacific Islander, Caucasian, and others—which has had significant impact on the U.S. standard for cancer prevention. We’ve been successful not because we bring the latest proton therapy to this remote part of the world, but because of diet, exercise, and education. By that we’ve been reducing the death rate in our area.
Phyllis: If anyone can meet the challenge, I feel confident that you can and will. I know you have transportation issues, language barriers, socioeconomic factors. I read that Native Hawaiians and Pacific Islanders often experience higher rates of chronic diseases such as diabetes and heart disease. So not only do you have that, you're also facing people diagnosed with cancer.
Dr. Ueno: During World War II, processed food was introduced. You probably know the food product called Spam—and this is not a criticism of Spam—but unfortunately because we cannot get fresh food to the area, a lot of people eat Spam and other processed food. That resulted in high obesity rates and the chronic diseases you mentioned—diabetes, obesity, hypertension—which impact the cancer rate.
Phyllis: That’s so interesting. Thank you for sharing that. Partnerships are central to your vision. Can you share how collaborations with health systems, community organizations, and global partners are strengthening cancer research and care in your region in Hawaii and the Pacific Islands?
Dr. Ueno: We have two components. We work with multiple health care systems, and I am the president of the Hawaii Cancer Consortium. We align the cancer service line by working together. They do compete, but at the same time they recognize that competing doesn’t help. That’s a real strength. It’s very unique—probably not possible in Houston or Dallas where competition is more intense. The second is that we reach out to Asian countries and work with the National Cancer Institute in Japan. We are in the process of joining the clinical trial network in Asian countries given the types of diseases we have.
Phyllis: As a cancer survivor yourself, how does that experience influence your leadership, research, and vision for the University of Hawaii Cancer Center?
Dr. Ueno: I want to make sure that regardless of research or non-research activity, the patient comes first. We all talk about it, but it’s very difficult to accomplish. When we plan care or research, we sometimes forget the patient and the community. One of the unique things we have is one of the best community advisory boards. We have a general board, but also separate ones for Native Hawaiian, Pacific Islander, and Filipino populations, and a Pacific patient advisory committee. These are not just committees—they’re engaged in research and community activities. Our community outreach engagement office is one of the best in the nation due to its long history. We’re trying to become a model even in the most challenging situations.
Phyllis: I knew you when you were going through your cancer journey and recall that you went back to Japan to have a bone marrow transplant. Is that correct? Do you want to talk a little bit about that?
Dr. Ueno: That is correct. When I was diagnosed with what we call myo displastic syndrome, commonly known as MDS, which is a preleukemic condition, I ended up needing a stem cell transplant. I was given a choice of receiving multiple treatments and eventually doing a transplant or doing it upfront. So it was basically slow death or fast. I decided not to get my treatment at MD Anderson. This is not because MD Anderson isn’t excellent, but you don’t want to get treatment from your colleagues. One thing I noticed at MD Anderson—they’re excellent—but they tend to overdo it because they want to do the best for you. Doing the best sometimes isn’t always a good thing. You want to be driven by evidence and knowledge. Sometimes as a patient we want everything, but a lot of times you don’t want everything, and sometimes you should wait. Waiting is always frustrating. Finding that right pace was important. My donor was not in Japan, so I decided to go there for the transplant.
Phyllis: Yes, knowledge is so powerful. I remember you and I were planning a benefit for the inflammatory breast cancer center, and while you were going through that you would call me from Japan. You kept working the whole time you were there, receiving your transplant. You are just so unique and competent in everything you do. My final question: looking ahead, what gives you the most hope for the future of breast cancer treatment and patient outcomes?
Dr. Ueno: I'm excited that I'm confused with so many new things coming up—that gives me hope. In the past 10 or 15 years, new things were coming, but not to the point that every four or six months something new comes and I’m scrambling to update my knowledge. There’s definitely a tsunami of knowledge. Digesting it is difficult, but that means it’s good. I think the future is that many people are working on different things and this tsunami will be amplified. I'm hopeful that multiple areas of knowledge will help cancer. We just talked about antibody drug conjugates and immunotherapy, but there are many other new modalities being explored. Eventually I think subsets of people who have advanced disease or rare and aggressive disease will have a true curable disease, and people will say, “Breast cancer is not a big deal.” I’m hopeful that will come within a decade.
Phyllis: It’s so important—breast cancer is something you go through, not a life ending event. I do hope within the next decade that will be what we tell everyone. Mahalo, Dr. Ueno. You are a distinguished professor, acclaimed author, TED speaker, brilliant researcher and deeply compassionate breast care oncologist. I am truly humbled and honored to call you my friend. May you continue to find success in all your endeavors. Your work has transformed and touched the lives of countless women and men facing breast cancer, and for that, I offer you my deepest gratitude.
Dr. Ueno: Great. Mahalo, aloha, Phyllis.
Phyllis: Aloha. Give my regards. I hope our paths cross very soon.
Dr. Ueno: Yep. Aloha, Phyllis.
Phyllis: God bless.
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