In Breast Cancer, Is Chemobrain Really 'Endocrine Brain'?

Kathy D. Miller, MD


June 22, 2020

This transcript has been edited for clarity.

I'm Dr Kathy Miller from Indiana University, here to make certain that you see a new publication from the TAILORx trial that was recently published in the Journal of Clinical Oncology.

You're likely all familiar with TAILORx, which is randomizing women with hormone receptor–positive, node-negative disease, and intermediate Oncotype DX scores (between 11 and 25) to chemotherapy followed by endocrine therapy or endocrine therapy alone. These recent results come from a subset of 552 patients in that study, in whom investigators analyzed the impact of therapy on their cognitive function.

Although we have all worried about patients with chemobrain, we've had very little opportunity to comprehensively study this in a prospective randomized trial. The TAILORx investigators provide us with that data. They used a well-validated, self-reported cognitive assessment tool (Functional Assessment of Cancer Therapy-Cognitive Function questionnaire) at baseline and at 3, 6, 12, 24, and 36 months.

Our patients will tell us that chemobrain is real, and these results—which are nothing short of fascinating—agree. Particularly in patients receiving chemotherapy, there was a prompt downward impact on self-reported cognitive function at 3 and 6 months. The effects had really leveled off by 12, 24, and 36 months.

What's fascinating is that there was also a decline in the patients who received endocrine therapy alone. Although patients who received chemotherapy reported more problems at 3 and 6 months, there was no difference between the groups at 12, 24, and 36 months. That lack of difference is partially due to some improvement in the acute effects of those receiving chemotherapy, but it is mostly explained by a slower but pervasive decline in those women receiving hormone therapy alone.

Other, smaller studies have also suggested that the phenomena we talked about as chemobrain might be more properly called "endocrine brain." If you do detailed cognitive function studies with MRI in women who are beginning hormone therapy, you will see significant changes in the brain regions that are important for the functions that our patients with cognitive impairment have the most complaints about.

These TAILORx data certainly fit with those smaller functional studies. And they give us valuable information to talk to our patients about the impacts of therapy on cognitive function. They show that the acute decline with chemotherapy does have some improvement and tends to level off. But it's also really important to acknowledge that even at 36 months, patients were not back to their baseline levels of cognitive function.

This also highlights a very critical questions that should be the focus of additional research: How do we minimize the impacts? How do we help patients improve? How do we help patients develop coping strategies for this critical long-term toxicity?

I recommend that you take a look at this manuscript. I think you'll find it equally fascinating.

Kathy D. Miller, MD, is associate director of clinical research and co-director of the breast cancer program at the Melvin and Bren Simon Cancer Center at Indiana University. Her career has combined both laboratory and clinical research in breast cancer.

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