Pulse
The Chemobrain Controversy
No one disputes that many cancer patients experience cognitive difficulties during and even after treatment. But should we blame chemotherapy?
By Jeanne Mettner
In Internet chat rooms for cancer patients, the personal accounts abound: A woman with breast cancer searches frantically for her keys, only to find them hours later when she opens the refrigerator and sees them perched on top of a container of leftovers. A patient with colon cancer drives to a destination and sits in the parking lot for several minutes trying to remember why she is there. A breast cancer survivor purchases several bags of groceries, wheels them to the car, then drives off before loading them in her trunk.
For years, cancer patients have swapped stories about the mental fog they experience before, during, and after chemotherapy. Somewhere around the mid to late 1990s, the mainstream media and breast cancer advocacy circles began referring to the phenomenon as “chemobrain.” More than a decade later, the term has stuck.
It’s difficult to determine how many people experience cognitive impairment during or after treatment for cancer, although some have surmised that at least 25 percent of patients who undergo chemotherapy are affected by symptoms of mild cognitive impairment. One study conducted by University of Minnesota researchers in 2005 reported an 82 percent rate.
What’s in a Name?
All told, the complaints about chemobrain are too common to be ignored. But is chemotherapy really the culprit? In 2006, researchers at the University of California, Los Angeles used positron emission tomography (PET) to assess brain function in 21 women who underwent treatment for breast cancer five to 10 years earlier. All of the women had surgery to remove their tumors, and 16 of the 21 underwent chemotherapy. PET scans revealed that the 16 women in the chemo group had a lower metabolism in the frontal cortex than the five women who did not receive chemotherapy, which, the researchers suggested, could explain the mental confusion afflicting many cancer survivors.
Other researchers have attempted to identify which agents are most neurotoxic—and potentially detrimental to mental alertness. In 2008, researchers at the University of Rochester’s School of Medicine and Dentistry in New York found that systemic 5-fluorouracil, a chemotherapy agent commonly used to treat colorectal, breast, pancreatic, and stomach cancers, causes a thinning of the myelin in the central nervous system that could lead to cognitive deficits resembling dementia.
For many physicians and researchers, however, the term “chemobrain” is a misnomer. “I think chemobrain is a horrible word; it’s a garbage bucket term for something that is real for patients but may not be associated at all with what its name implies,” says Timothy Moynihan, M.D., a medical oncologist with Mayo Clinic. “We haven’t yet pinpointed the causes or mechanisms of these cognitive challenges.” Moynihan says that anecdotally, breast cancer patients seem to be reporting symptoms more often than patients with other cancers—but again, there is no evidence to substantiate that observation or to explain why that is the case.
What Causes the Haze?
Determining the cause of cancer-related mental fogginess has proved difficult because there are so many potential variables. For one thing, numerous conditions that may coexist with cancer—depression, anxiety, stress, hormonal changes (especially with breast or prostate cancer treatment), and low blood counts—can have an effect on a person’s memory and ability to focus. Second, because cancer exists in a person’s body for an undetermined amount of time before diagnosis, it’s tough to determine a baseline from which to measure cognitive decline. In addition, everyone’s ability to concentrate varies dramatically from day to day, depending on the stressors they experience, the quality of sleep they get, and other factors.
Given these factors, the exact cause of cancer-associated cognitive changes is not likely to be identified anytime soon, particularly with the precision required to yield definitive results. “To be honest, there is so much going on at one time … that it’s very difficult to tease out exactly what’s going on,” explains Sadhna Kohli, Ph.D., an assistant professor of oncology at Mayo Clinic. “There are many things we need to look at it before we can confidently call it ‘chemobrain.’”
Further confounding the issue is the fact that objective measures of a patient’s cognitive function do not always corroborate their self-reported symptoms. Kohli has found this to be anecdotally evident in the breast cancer patients she evaluates. “In many cases, women may be complaining of cognitive difficulties; but when they actually go in to do the neuropsychological tests, their results show that they are still functioning in the normal range. For some reason, the two sources of data just do not correlate,” she says.
Kohli will look at why that’s the case in a new study, for which she is recruiting 33 newly diagnosed breast cancer patients. Before the patients undergo chemotherapy, Kohli and her team will gather baseline data from three sources—self- reported surveys, in-office neuropsychological assessments, and magnetic resonance spectroscopy (which measures brain metabolites). The researchers will follow up with the patients four to eight weeks after they complete chemotherapy, then again one year later, to observe any changes that may have occurred. “What we are hoping to see is a correlation between the patient’s self-report, neuropsychological test results, and brain metabolite measures,” Kohli explains.
More Survivors, Better Understanding
With close to 80 percent of breast cancer patients surviving 10 years after their diagnosis, clinicians are increasingly addressing issues of survivorship, one of which is cognitive function after treatment. “A lot of the complaints of cognitive challenges first came from breast cancer advocacy groups; they’ve helped people speak up,” says Moynihan, “and, for the most part, that’s a good thing.”
He explains that as more resources are dedicated to meeting and understanding the needs of cancer survivors, clinicians will likely get better at helping people with cancer-associated cognitive problems. In the meantime, patients should be encouraged to talk about the issue. “The more we see and hear about their cognitive challenges,” Moynihan says, “the more we are able to determine what we can do to help.”