Study Finds ‘Chemo Fog’ in Breast-Cancer Patients Is Real

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Many cancer survivors report feeling they’ve lost some mental sharpness following treatment. This common phenomenon has come to be known as “chemo brain” or “chemo fog,” which is somewhat misleading because it also occurs in people who have not undergone chemotherapy.

Although recent studies have shown that up to 75% of cancer survivors do indeed experience altered mental function — and that these changes can last for five years or longer — doctors often downplay complaints about chemo fog, says Shelli R. Kesler of the Stanford Cancer Center in Palo Alto, Calif.

“[Patients] often are told it’s not real, they’re imagining it, it’s just due to stress,” she says.

In a new study published this week in the Archives of Neurology, Kesler and her colleagues provide more evidence that the phenomenon is real. Using brain scans, the researchers found that breast-cancer survivors show changes in key aspects of mental function that can translate to real-world difficulties. And these changes were particularly marked in women who had undergone chemotherapy.

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Kesler’s team investigated prefrontal-executive function, the type of mental activity most commonly reported to go awry in breast-cancer patients. Executive function includes the ability to selectively pay attention, work with information, and choose the appropriate response while suppressing inappropriate responses.

The study included 25 breast-cancer patients who had undergone chemo, 19 breast-cancer survivors who didn’t get chemo, and 18 healthy women. While undergoing functional magnetic resonance imaging (fMRI) brain scans, the participants completed a brainteaser in which they tried to discern a pattern in a series of cards printed with colorful geometric shapes. The test, Kesler explains, measures “cognitive flexibility,” or the ability to identify the best solution to a problem by mentally testing several possibilities.

Overall, both groups of breast-cancer patients showed less activity than the control group in regions of the brain involved in executive-function tasks such as storing and processing information. And the chemo-treated patients displayed the least activity of any group in parts of the brain associated with cognitive flexibility — a result that was borne out by the card-sorting task. The chemo patients made the most mistakes on the task, on average, and they took the most time to complete it.

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The brain activity of the chemo patients was also closely correlated with how severe they judged their own post-treatment declines in mental function to be. This finding confirms that chemo fog is not imaginary, says Robert Ferguson, a clinical psychologist at Eastern Maine Medical Center in Bangor, who studies the phenomenon but was not involved in the new research.

“I have patients tell me, ‘I’m just working harder and I’m slower at what I do, and I have to check my work and I still find errors, even when I’m working methodically,'” Ferguson says. “This data is consistent with that anecdotal report.”

It’s not clear that chemotherapy is directly to blame, however. More than half of the patients in both breast-cancer groups took tamoxifen, an estrogen-blocking drug that also has been linked to cognitive impairment, and most of the women in both groups also underwent radiation therapy. Either treatment could affect the brain, Kesler says. Even surgery could be a contributing factor, because general anesthesia can have lasting effects on mental function, Ferguson says.

Finally, cancer could be harmful in and of itself. “When you get a disease like cancer, it activates your immune system,” Kesler says. “Sometimes you can have increased inflammation for a really long period of time, and inflammation can affect the brain.”

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Cancer-related changes in mental function tend to vary widely by patient, says James Root, a neuropsychologist at Memorial Sloan-Kettering Cancer Center in New York City, who studies cognitive impairment in cancer patients. “Treatment does not appear to affect all individuals equally,” he says. “Some go through treatment and exhibit no issues, while others are significantly affected.”

Researchers aren’t sure what accounts for this individual variation, although genes, age, biological factors, and the pre-cancer mental function of the patient could all play a role, Root says.

Sure enough, older cancer survivors in the study tended to have less brain activity than their younger counterparts in the areas targeted by the researchers. The amount of brain activity also tended to increase with the women’s level of education, which suggests that people who have strong mental function before cancer treatment may be somewhat protected against declines, the study notes.

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Kesler and her team are developing strategies for helping patients adapt to changes in mental function, and are conducting a clinical trial of a cognitive rehabilitation program they developed.

“The less mentally and physically active you are, the more likely you are to have these effects, which is something you can change,” Kesler says. “You can become more mentally and physically active. It’s hard because you don’t feel well and you don’t want to do these things, but there are programs that exist.”

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