Male Breast cancer impacts about 2,800 men each year, and while it’s very rare, male breast cancer can be more challenging to treat and has poorer outcomes. Complicating matters is the fact that there’s little to no data on how certain breast cancer treatments work in men. It’s an area that Dr. Jose Pablo Leone seeks to address. Dr. Leone and colleagues have launched ETHAN, a clinical trial to investigate whether—and how—various combination therapies work in this group.
Dr. Leone is a medical oncologist and clinical investigator in the Breast Oncology Center at Dana-Farber Cancer Institute, where he also serves as the director of the Program for Breast Cancer in Men. Dr. Leone’s research focuses on brain metastases, male breast cancer, and research involving large databases, and he has been a BCRF investigator since 2023.
Below is an edited transcript of their conversation.
Dr. Jose Pablo Leone: Breast cancer in men is overall a rare disease. It happens in about 1 percent of men, and it’s also 1 percent of the number of breast cancer cases that are diagnosed annually [in the United States]. Risk factors for breast cancer in men include older age. It includes sometimes exposures to estrogen or testosterone previously, hormonal differences in the balance between the estrogen and testosterone, some genetic conditions such as Klinefelter syndrome, for example. There’s also risk factors associated with prior exposure to radiation or carcinogens that can be seen as well.
JPL: So that is a study that we did a couple of years ago actually on a study that we published in the Journal of the National Cancer Institute where if we think about the history of breast cancer and the treatments that we have had for breast cancer, the majority of men are treated with mastectomy, and they are offered Tamoxifen. Those are treatments that we have been using in the treatment of women with breast cancer for more than 30 years, and so if we keep doing the same thing, we will probably continue to have the same results. With that hypothesis, we did an analysis of SEER data to try to see whether outcomes for men with breast cancer have changed in the last 10, 20, 30 years. So, we went back all the way to 30 years, and what we found is that outcomes have not improved, unfortunately, for men with breast cancer during that period of time as compared to the outcomes that we know have improved in women over that period of time.
We did notice, however, an improvement in overall mortality in men which is consistent with the improvements that we have seen in the healthcare overall and in the survival overall. So the longevity of the male population has gone up over time as it has been the case for the female population as well. So we have seen that, but we haven’t seen the improvements in the outcomes for breast cancer specifically. So looking at breast cancer specific mortality, those have not improved.
JPL: There are several aspects that are challenging. One is the fact that the disease presentation is overall uncommon, and when a disease is uncommon, it’s harder to gather high-level evidence on what to do. So, in our field, the highest level of evidence comes from randomized controlled trials, and those trials usually require a large sample size. It’s hard to get a large sample size of men with breast cancer to randomize them as we would normally to try to find out what is the best treatment option for the given question that we’re trying to answer, and that is one of the biggest challenges.
JPL: ETHAN is a clinical trial that we are running in very close collaboration, and thanks to the support from BCRF through a cooperative group called the Translational Breast Cancer Research Consortium (TBCRC). The ETHAN trial is a trial that is enrolling men with operable breast cancer stage 1, 2, 3 with hormone receptor-positive disease and is randomizing them to different endocrine therapy options of which Tamoxifen is the control arm because Tamoxifen is our current standard of care for the treatment of male breast cancer that is hormone receptor-positive.
We are comparing the Tamoxifen arm, the control arm to other options that have been known to be successful in women. So on the study, we’re trying to catch up with, essentially, 40 years of drug development in endocrine therapy for breast cancer which is what we know today for women with breast cancer, and we’re trying to use drugs that we know have been successful to hopefully be able to provide, at minimum, additional treatment options for men and at best, treatment options that actually improve outcomes for our patients.
JPL: To see somebody get cured of breast cancer is one of the most happy moments you can see as a doctor for me personally. Yet, you could have had the exact same approach, the same treatment recommendation to a different patient, and that patient, unfortunately, does not do as well, and that is very frustrating when we see that. Another part that is very frustrating is that we don’t always know why that happens. In fact, I would say most often, we may not know why that happens, why that is so different between the two patients. It’s an area that needs a lot of research to be done to understand not only why those differences exist, but also, how do we make them disappear? How can we actually cure all patients with breast cancer, the ones who were destined to do very well, but also the ones who were destined originally to not do so well? Hopefully, we have a treatment that will change that destiny to a cure.
JPL: I’m forever grateful for BCRF for all that they do and for the support that they have provided me. Without the support from BCRF, the ETHAN trial would never have happened. Before getting the support that we received from BCRF for the ETHAN trial, we had applied for support from other sources including industry, and we, unfortunately, would not be able to get the support that we needed to conduct the study had it not been for BCRF efforts. I just want to highlight that because this is something that many people will say that, “Had they not been funded by X organization or X resource, their research would not have happened.”
That is true in my particular case as well, but I want to highlight one thing that I think is more important which at least for me is that the research that we’re doing which we’re hoping to help the patients, particularly patients who do not understand how do we not know more for their treatment, which is specifically men with breast cancer, is research that virtually not many other places will want to support. BCRF has looked aside from the reasons of why other places would not want to support those studies and has yet provided the support, supporting the idea behind the study, and believing that this was something that can be impactful and that can be helpful to our patients. I have seen that from BCRF not only for my particular area of research, but also, many of my colleagues and investigators that have had their ideas and their projects supported by BCRF who are projects that are incredibly important and that otherwise would not happen.
And another thing that BCRF has been incredibly helpful with is a program that they have which is the Drug Research Collaborative where BCRF has partnered with different industries to bring a bridge of the availability of newer therapies and the academic interest in finding the best patients who will benefit the most from those treatments. I think that’s incredibly helpful, actually, because what happens is that BCRF has an enormous amount of knowledge about what is scientifically helpful and also valuable from a patient perspective from the various people that collaborate with these patient advocates, scientists, scientific advisors. So they will connect with industries to partner with them, and then hear proposals from scientists so that the collaboration can happen in a much more integrated way where otherwise it may not happen at all because the industry partners may not see the value that BCRF is seeing and is making possible. It all comes down to making it possible, which is what BCRF is facilitating, and that is, I think, immensely helpful.
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