Hackensack University Medical Center medical oncologist, Deena Graham, MD talks about how “chemo brain” could be attributed to inflammation.
Interview conducted by Ivanhoe Broadcast News in 2022.
For starters, for our viewers who may not be familiar when you’re talking about chronic inflammation. What do you measure? What are you looking at?
GRAHAM: Well, there’s various ways that we can measure chronic inflammation and we’re still actually discovering lot about the best ways to actually be doing that. The way that we measured it in this particular way is by blood tests. We look for something in the blood which is called a C reactive protein or what we call a CRP. I’m sure that there are, and I know that there are a number of different ways, but that’s specifically how we did it in this study.
And when you have is it high levels of that protein? What does that indicate?
GRAHAM: Honestly, it’s a pretty broad indicator of inflammation, which basically means like these inflammatory markers are proteins in your blood can be elevated when the body is under some form of stress. Physical stress, physiological stress, sometimes emotional stress though we’re not really sure. But it’s a very broad measure. It’s not specific at all to any one form of inflammation.
When you have this high inflammation, these high levels of protein, this inflammation over a period of time. What does that contribute to?
GRAHAM: Well, that’s a great question. I mean, I think that’s a bit of a holy grail question because we don’t really know where this study actually came from. Was first understanding that patients, particularly patients 60 and over that have been affected by breast cancer, develop or had reported cognitive or thinking changes after a breast cancer diagnosis and treatment. And that’s really where this study came from and it was developed to better understand why that would happen and also to systematically measure how it happens and to what degree. Once we establish that, then we started to try to understand why was that happening. It’s always been thought that inflammation can potentially have a connection between cognitive changes even in non-cancer patients. We have this cohort of patients that were affected by breast cancer at various stages and underwent various treatments. One of the things that we identified or looked for in their blood was these CRP levels.
You had mentioned various treatments and I’m glad you did because I was going to ask a lot of times. You hear about chemo brain. Well, if you had chemo, perhaps are those cognitive changes, is that fuzziness due to chemo but not every patient had?
GRAHAM: Correct. Exactly. I think in our population, not every patient had chemotherapy. Not every patient had anti hormonal therapy, which is another very common treatment that we use. Some patients had no treatment or didn’t require treatment or opted to not partake in treatment or so. This is a broad population of breast cancer patients 60 and an older. We definitely don’t have enough information to drill down to those different groups. But this is more so a way of trying to understand what happens and also hopefully be able to prevent it from happening.
Are patients complaining of this or are your older patients and cheese. I’m just not sharp or how did this come to light?
GRAHAM: Yeah. I think the term that you used before, chemo brain, brain fog. I mean, that’s something that we’ve been hearing about from patients for a very long time. And again, in some cases, irrelevant of what stage, what treatment, where they’re at in treatment. That’s again why we cast the big net with this study in an effort to try to better understand there’s so many of our patients have been telling us this. And other studies haven’t really had systematic ways of measuring that. Because as you can imagine that, it’s hard to quantify because people are coming in with all different levels of initial fogginess, if you will. But this study is trying to look at it very systematically again so that we can hopefully intervene. And as a physician that takes care of patients with breast cancer and has done that for most of my career. We see this. It’s not made up, it’s real, so we just have to understand it better so we can intervene.
Why is it so critical to get to the source of what could be causing this?
GRAHAM: I think that the critical thing about getting to the source is being able to treat it. And although this particular study looked at CRP levels and inflammation, I’m sure this not going to be one thing that causes this. I often tell people with cancer in general, the cancer and the symptoms that come from cancer. There’s a car and there’s a lot of people in the car and a lot of things that are contributing. At different times there’s a different driver and you have to identify that driver and shut that drive, but then it switches. It’s not as easy. Not easy, that’s probably not the right word, but I don’t think it’s going to be as simple as okay. If you can lower CRP levels than people don’t have cognitive decline. I actually think that the CRP level going up is a way that there’s something else causing that, that we have to get to. That being said, we know that there are some lifestyle things potentially that can lower, “inflammation”, like potentially better diet choices, exercise. We know from studies that those types of things can actually potentially lower CRP. And again, I don’t think that it’s going to be a one and done, but I think this is a step, it’s a step towards identifying scientific or biological predictors. Because once we have a biological predictor, we can come up with something to get rid of that. So even if it’s just a piece, getting rid of a piece is helpful.
Can you just walk me through the study itself, how many people are involved? How did you conduct it?
GRAHAM: Sure. So the study was conducted by identifying patients aged 60 and older that were diagnosed with any stage of breast cancer, including what we call pre-cancer or stage 0, which includes something called ductal carcinoma in Situ. And on the other side, it included patients with up to stage 3 breast cancer. And there were about 700 patients identified. And then we also identified something called controls. So controls are patients that are participants, I should say, that pretty much match up with the patients, but they don’t have cancer. So they do those same studies, those same types of cognitive exercises. And therefore, if there’s differences between the controls and the patients, primarily those are things that are related to the cancer and not to other things like age, race, socioeconomic status, educational status. Patients that had baseline cognitive issues or neurological issues were excluded from the study. So in other words, patients who had had a stroke or something like that where their baseline cognition was affected, we did not include those patients. And essentially, these patients went through a battery of cognitive testing, where they were tested at different time points along their journey, if you will. So at six months, 12 months, 24 months. And we extended the study a little bit into it to draw blood from patients because that’s how we’re able to get some of these other biomarkers because we realized that we would need something or it would be great since we have this, we call a cohort of patients, that we can study things. And patients were very willing to participate. And I would explain, this probably isn’t going to help you, but it can probably help someone who’s going to be like you in a few years. I’m always impressed with how our patients give at a time in their life when they’re really challenged, but they do and it’s amazing. So we then developed collecting blood specimens. And since that was an addendum to the study, some patients opted not to, some it was too hard to get the blood samples, but most of them did. We also followed a small cohort of patients had functional brain MRIs. That’s much smaller cohort obviously. But that’s essentially how the study was conducted. And then once you have this patient population, then we’re constantly looking at how we can look at that. And I think the great thing about this particular study is that it reaches across a lot of sub-specialists. So I’m obviously a medical oncologist, but we work with neuropsychiatric, neuroscientists, behavioral scientists, epidemiologists. So it’s really been a great opportunity to participate in this. And this a study that’s originated in Georgetown, which is our partner and our NCI Cancer Consortium designation. But there’s multiple institutions across the country that are participating.
Now that you have this information, this first piece, where do you see the research going from there? What’s the next thing you do? What’s your next step?
GRAHAM: I think the next steps are going to be exploring interventions that can lower these factors associated with cognition decline and see if they actually have a benefit in doing that. Now, obviously, people think, is there a medicine I can take or something like that? And there may be. But that’s also a little complex because then you’re introducing a medicine in addition to other cancer medicine. So I think we’re a bit aways from that, but that’s the point. I think we can identify something. Please take a bit of time. But that’s the hope of where we’re going with this. And who knows what else we will discover along the way.
Women are living much longer with breast cancer now. So again, the importance of being able to clear up the fogginess and the cognition problems. If you’re testing that 60, I would imagine.
GRAHAM: Yeah. Sixty is an old. You know what I mean? I think improving quality of life is huge because our patients are surviving, thriving, living longer. These are the things that when I see my follow-up patients, we want to help. I always tell them I don’t want to solve one problem and cause another problem. I think now that we’re aware of this, I’m sure in five, 10 years we’ll have some solutions and be able to help.
Is there anything I didn’t ask you that you would want to make sure that people know?
GRAHAM: I think the great thing is that the only way that we’re able to generate this information is by our patients having participated in clinical trials. And I can’t express enough gratitude towards my patients who, again, participate in these things at a time in their life where they’re scared and they’re still looking to provide this information for the help of others. And I think that’s just something that I’m so appreciative of and I know our patients are.
END OF INTERVIEW
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