Memory Problems Due to 'Cancer Brain' and Not 'Chemo Brain'?

Veronica Hackethal, MD

August 13, 2015

Memory problems and cognitive impairment in women with breast cancer have traditionally been blamed on "chemo brain," but a new study shows that there may be problems even before patients start on chemotherapy and suggests that cognitive problems may be linked to cytokines released by the cancer.

The study was published online June 22 in the Journal of the National Cancer Institute.

The study is the first to describe a relationship between cytokines and patients with newly diagnosed breast cancer who have not yet received any cancer treatment.

"Cognitive dysfunction in breast cancer patients has traditionally been attributed to the effects of chemotherapy ('chemo brain'). However, our findings indicate that it is present even prior to any cancer treatment," commented first author Sunita Patel, PhD, a clinical neuropsychologist at City of Hope Medical Center, in Duarte, California.

In general, "chemo brain" refers to the side effects of chemotherapy, whereas "cancer brain" includes cognitive problems related to many factors involved in cancer, including stress, she explained.

"It may be helpful for patients who are fearful about cognitive side effects of chemotherapy to know that new research suggests non-treatment-related factors play a role," Dr Patel added.

Study Details

In the study, Dr Patel and colleagues enrolled 174 postmenopausal women who had been newly diagnosed with breast cancer at City of Hope Medical Center. The women had not yet received any cancer treatment, including surgery, which can affect cytokine levels.

These patients were age-matched with healthy control women (n = 88).

Participants underwent comprehensive neuropsychological testing that assessed mood, fatigue, and cognitive function (including tests for executive functioning, processing speed, and memory).

The researchers also measured key cytokine levels: interleukin 6 (IL-6), interleukin-1 receptor antagonist (IL-1ra), and soluble TNF receptor type II (sTNF-RII). IL-1ra and sTNF-RII are plasma biomarkers for IL-1 and TNF, respectively, that can be measured more reliably in plasma than these cytokines.

Results showed significant reductions in memory in women with breast cancer compared with the control patients (P = .02). Of the cytokines measured, only IL-1ra was significantly increased in women with breast cancer compared with control participants (P = .007).

Analyses controlling for age, education, race, mood, fatigue, body mass index, and comorbidities revealed sTNF-RII as the only cytokine that was a significant independent predictor of worse memory functioning (P = .01). The relationship between higher sTNF-RII levels and worse memory function was significant in women with breast cancer (P = .04) but not in control persons (P = .44).

More than one third of the patients in the study had hypertension. Comorbidities such as diabetes and hypertension were linked to reduced cognitive processing speed and executive functioning (P = .03 and P = .03, respectively).

"The finding reinforces the importance of a healthy lifestyle to prevent the development of [chronic] health conditions, as they are also associated with behavioral symptoms," Dr Patel highlighted.

The study cannot reveal whether memory problems are directly related to breast cancer, she pointed out. It also did not take into account other factors that could affect cytokine levels, such as diet, nutrition, medications, and exercise.

"It is possible that the factors that led to the development of the cancer, like genetics, lifestyle behaviors such as physical inactivity or obesity, and other health conditions, may also contribute towards lower cognitive functioning in patients," Dr Patel explained.

"The really exciting part of this study is that it's an extremely carefully and thoughtfully conducted piece of research by a very strong group who has really pushed the envelope in assessing patients prior to surgery and looking at cognitive function," commented experts in an accompanying editorial. The senior author was Dana Bovbjerg, PhD, leader of the Biobehavioral Oncology Program at the University of Pittsburgh Cancer Institute, in Pennsylvania. Other authors were Carissa Low, PhD, and Pawel Kalinski, MD, PhD, also of the University of Pittsburgh Cancer Institute.

Although the idea of "chemo brain" has been around for a long time, studies looking at chemo brain did not consider the possibility that underlying mechanisms related to the immune system and the tumor environment could play a role. That is the "distinct novelty" of this latest study, Dr Bovbjerg told Medscape Medical News.

"The concept of chemo brain makes it sound like all of this is something that happened to you because of chemotherapy," he said, "In fact, this may be something that patients are experiencing because of the underlying tumor itself. That's this notion of 'cancer brain,' though both may be going on."

Understanding the mechanisms behind cognitive dysfunction and cancer biology could lead to new treatments to "block the biology," Dr Bovbjerg suggested. Possible treatments could include TNF blockade and therapies targeting IL-1 or IL-6.

"We need more research to know best how to do it," he cautioned, "We don't want to block immune responses that may be important for defense against cancer without knowing what's going on."

That said, Dr Bovbjerg emphasized that this is an initial study looking at women with newly diagnosed cancer, so it was not known how long the cognitive effects could last.

"It will be exciting to have future research take the work a step further and look more broadly at patient-reported information and how it might improve precision medicine," he concluded.

The authors, Dr Low, and Dr Kalinski report no relevant financial relationships.

J Natl Cancer Inst. Published online June 22, 2015. Full text, Editorial


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