Harold Burstein, MD, PhD, and other breast cancer experts at Dana-Farber discuss important breast cancer research presented at ESMO 2025.
I'm Doctor Harold Burstein from Dana-Farber Cancer Institute. Pleased to be with you today talking about some of the highlights in breast cancer research innovation that emerged at the 2025 ESO meeting in Berlin. That meeting turned out to be a huge stockpile of data for randomized phase 3 studies in early stage and advanced breast cancer, and we'll be talking with some of our experts here at Dana-Farber to get their take on what these data mean, how you should interpret them in the clinic, and where this field is going to be going. As you go through these several sets of remarks, I want you to think about 3 big themes that I identified in my review of this material that, that I think are really important for understanding what the data are telling us and where the field might be going in the future. The first is globalization of clinical cancer trials. So I've listed on this slide some of the major studies that were reported at ESO 2025, and I've identified the name of the study, the population of patients that went on to it, and listed the percentage of a. Rule by the world geography, North America, North America combined with Western Europe and the rest of the world, and you'll see a couple things right away. The first is that for most of these trials, the North American accrual was actually very small, only a modest percentage of all the patients, and in fact the rest of the world outside of North America and Western Europe constitutes a major fraction for all of these trials. That's the nature of pharmaceutical drug development in 2025. These are global companies and they seek to have their products approved by global regulatory authorities, almost all of whom want some clinical experience in their own populations. So on the one hand, this makes total clinical sense in the idea that we're gonna want to see data from all around the world, but there are problems here, right? Because one of the huge differences in cancer care around the world is that the United States has far more drugs available to patients, uses far more drugs. Their care and also has far more extensive palliative care options and supportive care measures and is willing to spend hugely when it comes to the resources and the care of advanced breast cancer patients compared to many other parts of the world. So when you're looking at these data, it's really important to ask if this is a global trial, does it meet our current standards of care? Are the comparators fair? Are patients getting access to all the drugs we would expect them to get? Secondly, it's important to ask what is the post-progression trial because the care received on clinical trial is usually very well spelled out in the protocol. But in patients whose tumor recurs despite that treatment or who progress on that treatment in the metastatic setting, there is a hodgepodge of different treatments available around the world, and few of them actually match the large armamentarian of drugs that are available in the United States. So when you start to look at secondary end points like overall survival, it's really important to know what did people get treated with. The second major theme that emerges in all of these trials is really the abundance of drugs that we're seeing in two particular classes. One is antibody drug conjugates and the other are selective estrogen receptor degraders or SERDS. So on the one hand, this is incredibly exciting. We're seeing lots of these new drugs emerging. There are at least 5 SERDs that have data for them from randomized phase 3 trials, and there probably are at least 4 or 5 ADCs that are in a similar position. So the question you want to be asking is, is this a plethora or a surfeit of those drugs? Now, before you search Merriam-Webster, I'll help you out. Plethora means an abundance, surfeit means too many. And so the key question is, are we really looking at a situation where there's genuine innovation going on, or are we just looking at an endless number of the same kinds of drugs? That's really important for understanding how we're going to select these drugs in clinic. It's also important to emphasize that as these drugs get approved, we want to make sure that patients who are getting them, say, in first line in a randomized trial and are not assigned to that drug would still get them in second line, something you want to pay attention to. And the third point that emerges, particularly in the area of hormone receptor positive breast cancer is the importance of combination therapies with endocrine agents and targeted agents. Historically, for a long time, it had been endocrine monotherapy with one line of treatment after another. Tamoxifen, aromatase inhibitors, and alvestriant were the mainstays of our care. But now for women who have advanced ER positive breast cancer, we're almost always talking about multiple lines of combining endocrine therapy, choosing one from column A, if you will, with a targeted drug from column B. So the endocrine options can be aromatase inhibitors or fulvestriant or the new and emerging class of SERDS, and the targeted therapies can be CDK46 inhibitors, typically in first line, and then in second line and beyond. PIC 3 CA inhibitors, MTOR inhibitors, repeat use of CDK 46 inhibitors as a class, and then cycling through all these drugs in some combinations. So that's a radical change in the paradigm for how we've been thinking about ER positive advanced breast cancer. So remember those things globalization and its impact on the patient population and the access they have to drugs. The emerging number of very similar products and how we're going to figure out where they each fit. And finally, the shifting paradigm for ER positive metastatic disease, looking principally at combinations instead of monotherapy. With that introduction, let's meet our experts.
