Study Shows Brain Changes After Chemo

Years after chemotherapy, some breast cancer patients have subtle memory and concentration problems often dubbed “chemo brain,” a new study shows.

The study, published in Breast Cancer Research and Treatment, comes from researchers including Daniel H. Silverman, MD, PhD.

Silverman is the head of neuronuclear imaging and is an assistant professor of molecular and medical pharmacology at the University of California, Los Angeles.

“Over the last half-dozen years or so, there has been this increasingly recognized phenomenon of what is often termed ‘chemo brain,’” Silverman tells WebMD.

He says patients describe chemo brain as “an impairment in their cognitive abilities -- to attend to things, and to concentrate, and to multitask.”

“What’s been missing from this, though … is looking directly at the brain -- what’s going on inside to account for that,” Silverman says.

The new study “represents the first direct look at brain metabolism associated with these chemo brain problems,” Silverman says.

Chemotherapy and Breast Cancer

About the Study

Silverman’s team studied 24 women, including 21 breast cancer survivors.

The women were about 47-58 years old, on average. The breast cancer survivors had been diagnosed with breast cancer an average of seven years earlier.

All of the breast cancer survivors had gotten surgery to remove their tumors.

Eleven survivors had also gotten chemotherapy and taken the drug tamoxifen. Five others had received chemotherapy but hadn’t taken tamoxifen. Five more breast cancer survivors hadn’t received chemotherapy or tamoxifen.

The study took place five to 10 years after the women’s last chemotherapy dose.

The women got positron emission tomography (PET) scans of their brains while taking two memory tests.

In one test, each woman looked at a complex drawing and tried to copy it with pen and paper, first while looking at the drawing and then from memory.

In the other test, each woman was shown pairs of words that they had to recall when the pairs were jumbled on a computer screen 10 minutes or one day later.

“They’re hard tests,” Silverman says. “It takes that kind of difficult challenge to be able to bring out these subtle deficits.”

Control Chemotherapy Nausea & Vomiting

'Sluggish' Areas of the Brain

The women who had gotten chemotherapy tended to have lower scores on the memory tests. Their PET scans showed slower metabolism in several brain areas.

That is, those brain areas were more sluggish than the same brain areas of the women who hadn't had chemotherapy.

Those who had gotten chemotherapy and who had taken tamoxifen had the lowest test scores. They also showed a metabolism slowdown in a brain area called the basal ganglia.

“Even five to 10 years after their last dose of chemotherapy … we find that there are specific areas of reduced metabolism in the brain that correlate with their reduction of cognitive function, particularly remembering,” Silverman says.

However, “a lot” of the women still had normal test scores, Silverman says.

“Part of it is that these women are oftentimes very high functioning to begin with,” Silverman says.

“It’s not like anybody ended up going from an IQ of 120 to [an] IQ of 80,” he says. “These are really relatively subtle changes.”

“But what we found was that there was this direct correlation so that the lower that they were on this neuropsychological test, the less metabolism they had in this particular part of the brain,” he says, referring to the women who had had chemotherapy.

Chemotherapy for Colorectal Cancer

Questions Remain

The study has some limits.

For instance, the women were tested years after their breast cancer treatment. So it’s not known how they would have scored on those tests before treatment.

Also, the findings don’t prove that chemotherapy or tamoxifen were responsible for the results.

“We can show the correlation, we can show where in the brain these effects are being localized,” Silverman says.

“But in terms of the mechanism about what’s causing that brain damage to occur … that’s still a mystery that’s being explored by us and others,” he continues.

The researchers have received a five-year grant from the National Institutes of Health to follow a larger group of patients “from the time they’re first getting their chemotherapy to years afterwards,” Silverman says.

Next Steps

If the larger studies bear fruit, it may be possible to use brain imaging to help select therapies and monitor patients “as they go along,” Silverman says.

“That’s actually quite feasible,” he says, explaining that “the changes in the brain metabolism are very sensitive,” so monitoring the brain may provide plenty of lead time to head off problems.

Silverman also notes that some breast cancer patients get whole-body PET scans “to be able to look at where the cancer may have spread and to monitor the response of the tumors to therapy.”

“And so all you would need to do is just spend an extra few minutes just sweeping to the head and get a picture of the brain. Usually the whole-body PET scans just stop at the base of the skull,” he says.

Chemotherapy is strong medicine to help halt breast cancer and save lives. The researchers aren’t suggesting that anyone skip chemotherapy based on the study’s results.

“It would probably take a much less subtle change in brain function to make that a worthwhile trade-off,” Silverman says.

By Miranda Hitti, reviewed by Louise Chang, MD

SOURCES: Silverman, D. Breast Cancer Research and Treatment, October 2006; vol 99. Daniel H. Silverman, MD, PhD, head of neuronuclear imaging; associate professor of molecular and medical pharmacology, University of California, Los Angeles Medical Center.