"I think this chemo is affecting my brain," a middle-aged patient told me last month. She went on to describe uncharacteristic difficulty in concentrating, and lapses in her memory. "I used to be a whiz at the daily crossword, but ever since I started my treatments I keep groping for answers to the clues," she lamented.

For years, oncologists have heard similar complaints and wondered….can chemotherapy significantly affect brain function? Despite not knowing the answer, we have tended to reassure our patients that everything will settle down once treatment is behind them. After all, we have reasoned, such problems aren’t necessarily due to the chemotherapy. Being diagnosed with cancer very often leads to anxiety, depression and insomnia that can decrease alertness, decision-making, concentration and memory.

But now, a new study published in the Journal of Clinical Oncology goes a long way in verifying that my patient's concerns truly have a basis in fact: chemotherapy may not only affect brain function, but its structure as well!　

In this small (69 patients), but exceedingly well-designed study, Belgian researchers assessed the effects of chemotherapy on the central nervous system by pairing a battery of neuropsychological (NP) and cognitive function tests with a powerful type of MRI scan, called magnetic resonance diffusion tensor imaging (DTI). By measuring the movement of water molecules, DTI can detect microscopic physical changes in the complex nerve pathways running through the brain’s white matter.

The scientists studied three groups of subjects: 34 premenopausal women with early-stage breast cancer who underwent chemotherapy after surgery; 16 similar women who did not have chemotherapy, but received the anti-estrogen drug, tamoxifen; and 19 age-matched healthy women.

For comparison purposes, each group was tested twice. The 34 breast cancer patients who received chemotherapy had their first paired assessment (NP/cognitive tests plus DTI) after surgery, before starting the chemo treatments, and again 3 to 5 months later, after the treatments had finished. The group that received only tamoxifen and the group of healthy controls were also tested at two intervals that matched those of the patients who underwent chemotherapy.

The results? The 34 women who underwent chemotherapy scored significantly worse on the second set of NP/cognitive function tests that measured attention, psychomotor response times, and verbal memory. In comparison, the 16 women receiving only tamoxifen and the 19 healthy controls all scored the same or better on retesting.

Moreover, the follow-up DTI scans in the chemotherapy group, but not in the other 2 groups, now showed a significant change in the nerve structure in the white matter of three brain areas (the frontal, parietal and occipital lobes) that govern these exact functions.

"Physicians sometimes tell [their patients] that they are just imagining the problem….there really is a problem. It's not just stress. It's not their imagination. It's a real brain change," commented Stanford University’s Dr. Shelli R. Kesler. Earlier this year, she and her colleagues published an MRI study in the Archives of Neurology that found that chemotherapy for breast cancer resulted in changes in brain activity in the prefrontal cortex, the area that governs decision-making.

In an editorial accompanying the Belgian researchers’ paper, UCLA oncologist, Dr. Patricia A. Ganz, noted that, while the period of follow-up was relatively short, and that all the findings could resolve over time, "we can no longer deny the existence of this….effect of cancer treatment..."　

She also pointed out the uncertainty as to whether the changes resulted from a specific drug used in the breast cancer treatment (one of them, 5-fluorouracil, is known to diffuse into the brain), or represented a more general effect. If caused by a specific agent, "regimens that may be more strongly associated with….cognitive changes could be avoided [in the future]," Dr. Ganz stated.

So, in answer to the question of whether "chemobrain" exists, the emerging data strongly indicate that it does. How long does it last? We don’t yet know. Much research is needed.

In the meantime, should women with early breast cancer refuse chemotherapy over worry that they will suffer a significant permanent decline in mental function? I would strongly caution that such fear is likely overblown. As Dr. Eric Kandel explains in his book, In Search of Memory, the human brain has tremendous plasticity, meaning that its structure is constantly changing and adapting to everyday mental stimuli such as learning, experiencing, and remembering new facts and events.

As a result, I suspect that longer-term studies will show that, with time, a majority of patients make a significant, if not complete, recovery from any adverse effects of chemotherapy on the brain. How can I be sure? I can only tell you that, based on my follow-up of many hundreds of breast cancer survivors over the years, good cognitive function, similar to the general population, seems to be the rule rather than the exception.