Women on chemotherapy for breast cancer may have tiny memory and thinking impairments compared with cancer-free women more than 20 years after their treatment, Dutch researchers have found.

Previous studies have suggested some women may experience "chemo brain" during or after treatment, but the new report is the first to test them so many years out, researchers said.

Still, the findings can't prove that chemotherapy itself is to blame for any changes in mental dexterity, and the differences in women who'd received the cell-killing treatment were "subtle."

"These are not people who are showing signs of what we would consider to be serious cognitive impairment or even mild cognitive impairment necessarily, they simply are scoring a little bit lower" on thinking and memory tests, said Barbara Collins, a neuropsychologist who has studied chemotherapy-related cognitive changes at Ottawa Hospital in Ontario, Canada.

However, even small effects could mean that farther down the road, these women might have a higher risk of more serious cognitive decline if their brain reserve has taken a hit, Collins, who wasn't involved in the new work, told Reuters Health.

Researchers said it's possible that chemotherapy drugs can cross from the blood into the brain and kill cells there, or that the medicine's effect on the immune system or inflammation could be linked to cognition.

To get more clues about the drugs' effects, Sanne Schagen from the Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital in Amsterdam and her colleagues gave 196 breast cancer survivors a series of thinking and memory tests. Those participants were between 50 and 80 years old, and an average of 21 years post-chemotherapy.

The researchers compared scores on the assessments of processing speed, word memory and general functioning with those from about 1,500 women who had never been diagnosed with breast cancer and were part of a larger, long-term study.

On a total of 17 tests, the women who'd had cancer and chemotherapy scored lower than the comparison group on seven of the tests, and similarly on the other ten.

The differences tended to be small. For example, the women who'd had chemotherapy scored an average of 24.3 out of 45 on word learning tests, compared to 25.5 in those without a cancer history, the research team reported Monday in the Journal of Clinical Oncology.

"Whether or not people notice these differences really depends on what you're doing in your daily life," Schagen told Reuters Health.

"A slight change in cognitive functioning can mean a lot for a person who is really depending on their cognitive functioning in a highly demanding job, but for someone who's retired and has a more relaxing lifestyle, this can go unnoticed," she said.

Researchers said that the chemotherapy regimen used by women in this study, cyclophosphamide, methotrexate and fluorouracil (CMF), is no longer frequently used as a combination treatment, but some of the drugs are still prescribed on their own.

Schagen said she would expect to see the same effect in women treated with more modern drugs.

The study can't prove that the chemotherapy was to blame for thinking and memory changes, rather than the cancer itself or other treatments.

One recent study suggested that women who'd had breast cancer did worse on cognitive tests a few years later, whether they had been treated with radiation and chemotherapy or radiation alone (see Reuters Health story of December 12, 2011).

The researchers also didn't have information on women's mental function before starting the drugs -- so it's possible their scores were different to begin with.

Cancer and neuroimaging researcher Brenna McDonald, from the Indiana University School of Medicine in Indianapolis, said that the patients she sees have the most problems within a few months of chemotherapy, and typically complain about trouble with multi-tasking or needing extra time to pick up new information.

"Certainly not all people that receive cancer treatment have these problems," she told Reuters Health, and many who do seem to improve with time.

The researchers agreed that the chance of having a little more thinking and memory trouble in the long run isn't worth considering skipping chemo.

"I don't think anyone in this field is saying, this should lead someone to not choose the treatment they need," said McDonald, who wasn't involved in the new report.

Still, she added, it can help cancer patients to know that "chemo brain" could be a side effect of cancer treatments, so they can see their doctor if they're having trouble.