William J. Gradishar, MD, discusses how far the breast cancer field has advanced over the last 20 years and the data he is anticipating to read out in the future.
William J. Gradishar, MD
Over the last 2 decades, the treatment paradigm of breast cancer has significantly evolved, according to William J. Gradishar, MD, chair of the 20th Annual Lynn Sage Breast Cancer Symposium.
During the Lynn Sage Distinguished Lecture at the symposium, he addressed some of the biggest advancements in breast cancer, while also pointing out a few developments that did not pan out as hoped. Overall, the field has advanced significantly, particularly in the HER2-positive subtype.
“Twenty years ago, we were just starting to appreciate that [HER2 positivity] was a distinct entity,” Gradishar said. “And even though we didn’t necessarily recognize it, we didn’t really have much in the way of therapy than any other kind of breast cancer.”
Now therapeutic options for these subtypes and others of breast cancer have moved the needle forward. Some of the most practice-changing additions Gradishar discussed are combination therapies, anti-hormonal agents, and checkpoint inhibitors.
In an interview with OncLive, Gradishar, chief of hematology and oncology in the Department of Medicine, Betsy Bramsen Professorship of Breast Oncology, and professor of medicine, Robert H. Lurie Comprehensive Cancer Center of Northwestern University, discussed how far the breast cancer field has advanced over the last 20 years and the data he is anticipating in the future.Gradishar: When we started the symposium 20 years ago, it almost perfectly corresponded when the National Comprehensive Cancer Network (NCCN) guidelines started as an institution—as an enterprise—to develop evidence-based guidelines. I thought that would be a nice starting point for my lecture. Then, I reflected on how things have changed over the last 20 years.
There have been things that we thought were going to be extraordinarily promising that turned out to be busts, and I revisit some things like that, with respect to bone marrow transplant, endogenous inhibition, a variety of different things. One of the themes that came up in my talk was that we have made remarkable progress. We haven’t necessarily hit home runs, with respect to changing the course of how we approach patients with either early- or late-stage breast cancer. In this case, how I approached my talk is from the medical oncologist’s standpoint.
The things we thought were going to be extraordinarily promising, [which could] basically put an end to our careers, really didn’t come to pass. What we have seen has been steady incremental improvement in terms of outcome, steady improvement in the number of options patients have, and by extension, many more possibilities for optimizing patients with both early- and late-stage disease. I highlighted the different buckets of breast cancer, how we have evolved away from chemotherapy, and even though chemotherapy still remains foundational, we have probably maxed out on what it can accomplish. Now, we focus on the incremental and steady improvements in antihormonal therapy, anti-HER2 therapy, and then of course, the promise of new therapies that will be coming along, including immunotherapies.Over the last 20 years, we have seen an area of breast cancer that didn’t exist 20 years ago, which is HER2-positive disease. We have seen an explosion of therapeutic options for patients that resulted in a completely different way that the disease is treated. Furthermore, it has improved the outcomes remarkably, both in patients with advanced- and early-stage disease.
Similarly, for antihormonal therapy, we had a couple of options 20 years ago, but the number of options has expanded significantly. The thing that has changed the most recently is partnering anti-hormonal therapy with targeted therapy, which has resulted in markedly improved outcomes. These kinds of therapies are now making their way into the adjuvant setting of estrogen receptor—positive breast cancer.
In some ways, in the last frontier where we have chipped away but not necessarily made a staggering improvement in outcome, is in triple-negative breast cancer (TNBC). We heard throughout this meeting that TNBC is not a monolithic entity but a variety of different diseases under the moniker of TNBC. Part of the challenge is trying to figure out the drivers in each of those entities within that subset and trying to identify therapies that can enhance outcomes. One regimen that appears most promising, which again won’t be a homerun but will improve the outcome, is checkpoint inhibitors plus chemotherapy.We [are] within a very short time frame of data to be presented at the 2018 ESMO Congress, where we will hear more on the use of CDK4/6 inhibitors. We will hear about survival data related to clinical trials, or at least 1 where a CDK4/6 inhibitor plus an anti-hormonal therapy has impacted survival. We have known for some time that there is a marked improvement in progression-free survival, but now we are talking about overall survival.
The second presentation related to breast cancer at the 2018 ESMO Congress will be the first randomized trial that incorporates a checkpoint inhibitor to chemotherapy versus chemotherapy alone in patients with TNBC. We have known since July 2018 that that trial is positive, but we will see the full data at the meeting. We will be able to judge the success of that trial and whether it is something that is clinically meaningful for our patients. We don’t have that data yet, but within 2 weeks we will.We are involved in a number of different trials that are looking at immunotherapy in breast cancer, both in the early- and late-stage settings. We are doing a number of trials with CDK4/6 inhibitors as well as targeted therapies that work on signaling the abnormalities and particular pathways [such as] ATK inhibitors. These will likely not be stand-alone therapies if they are successful, but partnered with other agents—either anti-hormonal, chemotherapy, or even immunotherapy. It’s still early to know what impact those treatments will have.From its origins 20 years ago, the conference has always been meant to educate physicians, who take care of patients in the community, on how they could take the new advances and how they would apply those to patient care. We view this as multidisciplinary, so we hear about surgical oncology, radiation oncology, medical oncology, genetics, etc. What the meeting has demonstrated is that in each of those domains, there has been a significant improvement that has resulted in a change in how we approach patients, not just compared with 20 years ago but even within the last year. We try to update people who need to know this information because most of the care for breast cancer is done in the community, not at academic centers.
The takeaway messages are multiple, but in each of those areas of specialty, we have changed how we do things. We use shorter durations of radiotherapy, we do axillary dissections sparingly now, and we have a variety of new systemic therapies that have changed the outcomes in a favorable way for both early- and late-stage disease. There are a number of things that have changed even since last year.