In terms of the background, so how I came to study this particular medication is I have always been very interested in prevention. And one of the challenges in breast cancer prevention is that currently the medications we have for prevention, most women really don’t like to take them because they can have some side effects that they don’t like, like hot flashes and younger women or older women, they can have issues with it, like, it can impact their bone density...
In terms of the background, so how I came to study this particular medication is I have always been very interested in prevention. And one of the challenges in breast cancer prevention is that currently the medications we have for prevention, most women really don’t like to take them because they can have some side effects that they don’t like, like hot flashes and younger women or older women, they can have issues with it, like, it can impact their bone density. You know, they can have joint aches. And so when one of my research collaborators came up to me and said, oh, you know, I’m working with this company who’s developing a drug that prevents hot flashes and osteoporosis. So something that makes women feel better. And he’s like, oh, you know, I wonder if it has any preventative properties. And I was like, wow, you know, that’s really exciting, you know, to think that something that could actually, that actually makes women feel, that’s developed to make women feel better, like maybe it could have these additional benefits. So that’s how I really got involved in the project. And, you know, just as I mentioned, the drug itself, I won’t talk about what company it comes from. The drug itself is FDA approved in the United States for hot flashes, and osteoporosis. And it’s been FDA approved for about 10 years. And it was originally developed as an alternative to combination estrogen and progesterone therapy, just because of some of the concerns patients had with breast cancer risk and endometrial cancer risk and et cetera. So that’s how the drug came about. Anyway, a little bit about the study. And so the type of study that we developed was it. So it was a window of opportunity study. And we chose to study DCIS because DCIS is a non-obligate precursor of invasive breast cancer. So about 25 to 30 percent of women who develop who have DCIS will go on to develop invasive breast cancer in the future. So we thought it was a good model for this idea of does our medication, conjugated estrogens and bazedoxifene, or I call it CE/BZA for short, does this medication, can it potentially prevent breast cancer? So we thought it was a good model for prevention. And the other nice thing about the model, the window of opportunity study and studying DCIS, is these women all undergo surgery, right? So they have a diagnostic biopsy and they’ll have surgery. So you have tissue available at baseline and at surgery, and the patient doesn’t have to have any additional biopsies. Uh, so that’s, you know, and, and you are, and that patient is, you know, there is usually a window of time, like three to four weeks between, um, you know, between when they see, when the patient sees you and when they have surgery. So you have this great time that you can use, um, to study this medication. So, the other good thing about our model is that it, um, the other thing about the DCIS model is, you know, you can study both the epithelium and the stroma. And so this is one of the other areas that we’re studying, you know. So we, you know, our primary goal of the study was to look at epithelial proliferation, if our medication could decrease epithelial proliferation. But there is also some preliminary data that suggests that it could also impact the stroma and it could also be protective in the stroma. So we have the benefit of studying both, you know, both the epithelium and the stroma with a DCIS model. So that’s how we chose this particular model. And, you know, so women, we recruited women, they took this medication for three to five weeks before surgery. And we had a variety of endpoints. Again, the primary endpoint was the proliferation, which we measured by protein expression of Ki-67. We also looked at HER2 expression, which we’re still analyzing. We looked at RNA sequencing to look at expression profiling. We looked at quality of life, again, which is very important in the prevention setting. And then we’ve also, we’re still have some ongoing analysis with our stromal biomarkers through multiplex staining. So that’s just a little bit about the study. The study, you know, took seven years to complete. We had some time, we had a little bit of delay with COVID, but we, you know, it was from 2017 to 2024. and then we had originally wanted to recruit 140 patients and we got 141. So we were able to meet our target. Some patients drop out for various reasons. I think one of the bigger reasons was COVID actually with scheduling, patients getting, you know, being sick and missing their window. And then, you know, in terms of the data and analyzing our primary aim, patients, sometimes, you know, we lose some patients because they’re, because we don’t have any tissue left after surgery. It’s all removed at the core biopsy. So, there was about, you know, there was, I would say, about 20, 19 patients didn’t have tissue at their baseline or surgical biopsy for us to analyze. So we ultimately analyzed about 94 patients, and we found a statistically significant decrease in Ki-67. Our p-value was 0.016, so it was very significant. And in terms of the absolute reduction, it was 4.5% reduction in Ki-67. One of the other things, as I mentioned, we looked at quality of life. And so we looked at two different measures. One of them was this breast questionnaire, which has
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