I’ve read a lot about “chemo brain” in breast cancer blogs. A lot of breast cancer patients observe a decline in their attention and memory during and after chemotherapy. They complain to their physicians and many of them feel invalidated by the responses they receive. This is in part, because the evidence of chemo brain is sparse. (Before you throw your shoe at your computer, bear with me.)

I have a Ph.D. in psychology and in addition to my seven years of graduate school during which I conducted research, I worked as a researcher for 10 years after I graduated. One of the things that researchers are trained to do is to test hypotheses and sets of hypotheses. In clinical research, there is also the testing of treatments in the context of clinical trials. We are trained to interpret hypotheses in terms of whether they are empirically supported or not. If they are supported in multiple studies, we accept them as “truths” (there are no absolute truths), especially if findings are replicated by another lab. If they are not supported, we conclude that (1) the hypothesis was incorrect or (2) the hypothesis was tested incorrectly.

However, there is a third reason why a hypothesis has inadequate research support and that is when the hypothesis has not been adequately tested. Now as far as I can see, this is the case for the chemobrain hypothesis. So does the fact that it does not have adequate experimental support mean that it doesn’t exist? No, it means that it could exist but we don’t know because we haven’t thoroughly looked at the question. A downside of our careful and methodical ways is that we take our sweet time assessing potential “truths.” This is also a source of frustration for most of the rest of the world. Further, sometimes as researchers or as clinicians who do evidence-based practice, we lump all of the hypotheses that have not yet been deemed empirically-supported into the same group. For example, when asked, “does treatment x work”, they might answer “no” even for a treatment that has never been tested. The correct answer in this case is “We don’t know.” As a clinician who is supposed to have the answers, it is hard to say this to people. But it’s part of our job. To the great credit of my oncologists, they are both extremely knowledgeable but honest about the limitations of their respective fields. My breast surgeon actually discussed the concern about over treating breast cancer because they do not yet know how to distinguish between tumors that will spread verses those that will not. (In breast cancer, an estimated 25% of tumors never spread. If you want this article, let me know. I have the .pdf and it was given to me by a childhood friend who is a professor at Rutgers and does cancer research on polarity in cancer cells.)

Then there is the confusion provided by some (not all) of the folks in the media who go around spreading rumors and making generalizations based on one small result from a single study. Or who totally misrepresent the findings of a research study. Unfortunately, most of us do not have university library privileges that allow us to check out the primary source material on which the story is based. Also, even if we could, we might not have the necessary background knowledge to interpret the study. As an example, there was a news story that made it rounds in the blogisphere recently. The investigators used used neuropsych measures and found that breast cancer patients who underwent chemo showed declines in executive functions such as memory. The comparison group were “healthy controls.” So a group of women who have been subjected to a variable onslaught of chemo, surgery, radiation, endocrine therapy, not to mention the stress of having a serious illness were compared to women with no known medical problems. The story was presented as evidence of chemo brain. This is not specific evidence of chemo brain because chemotherapy was one of many variables that could explained the findings. Does this make the study useless? No, I think it shows that the cancer assessment and treatment experience is associated with a decline in cognitive functioning. It is a little bite out of a much larger question. Further, the use of neuropsych measures was really smart. They can be more sensitive to subtle real world changes than other measures plus they are safer and probably less expensive (I’m guessing that they did not do a full neuropsych battery, which is kind of expensive) than using an MRI.

Boy, I wish I could remember where I saw that article but I can’t remember where I saw it. That’s because my attention and memory have been impaired since I was diagnosed with breast cancer nearly a year ago! As a psychologist, I validated this for myself as the stress alone of having cancer is enough to impair executive functions. And also as a psychologist, I don’t dismiss the real impact that stress can have on a brain. In simple words, psychological stuff is real. People might say, “It’s all in your head.” Guess what? Your head is part of your body. Also, your brain is in there and it’s kind of an important organ.

Stress impacts cortisol regulation. Cortisol is a hormone that is triggered by stress and it’s purpose is to help us function better during those “fight or flight” times of our life. A problem with this is that too much stress or chronic stress can break down this regulatory system and lead to a break down in attention and memory. Speaking of hormones, there is another hormone that is thought to be important in memory functioning and that hormone is estrogen. Most, but not all breast cancer is estrogen responsive. How many of us have our cancer treated with hormone blockers? So at least some of that fog could be due to reduced estrogen. I am not an endocrinologist and concede that I am oversimplifying the role of these hormones to make my point and also because I don’t understand endocrinology terribly well. But my larger point is that there is evidence that (1) cortisol and estrogen functioning impact attention and memory and (2) cortisol and estrogen functioning is impacted by having and being treated for cancer. And theses are just examples. There are a lot of potential mediated relationships (indirect effects) as well. Interrupted sleep impairs attention and memory, too. How many of you haven’t had difficulty sleeping due to the stress of cancer or due to increased hot flashes, for those of you who receive endocrine therapy?

But what about chemotherapy? All of my chemical warfare has been in the form of anesthesia, pain meds, tamoxifen, and Lupron. I did not receive I.V. chemotherapy. My heart is with all of you who are enduring or have endured this. It’s not unreasonable to hypothesize that chemotherapy drugs might have a direct negative effect on memory and attention. The blood brain barrier does not exactly work like Fort Knox in keeping chemo drugs from entering it. There is some permeability. So at least some of those nasty chemicals might get in and do damage. (I’m not a neuro-pharmacologist or neurobiologist but I believe that my general point is true.) And perhaps some of that damage might be to parts of the brain that impact attention and memory. And I do see some research in my Google Scholar searching that supports these hypotheses. But one job of a researcher is to interpret findings from a single study into the larger context of multiple studies. They also use the level of rigor of the particular journal in which the article is published in their interpretations. I can do this in my own field but this is after many years and having read thousands of research studies.

One question that is buzzing around my head like a gadfly is “Why isn’t this question rigorously tested?” If any or all of the chemotherapy drugs cause cognitive decline, shouldn’t we investigate it so that patients can be informed of the potential treatment side effects? Isn’t it important to know whether the potential effects vary in duration, frequency, or intensity as a function of the drugs chosen for treatment? And in the mean time, let’s hear it for better integration of psychology into cancer research and treatment. I think we can all agree that cancer is stressful. We also know that it increases risk of anxiety and depression. Stress, anxiety, and depression can all negatively impact attention and memory. We have tools for addressing these issues and some of them like mindfulness meditation are incredibly cheap and safe. Finally, we are trained in measurement as well as in research design and clinical trials.