More people survive cancer than ever before. With early detection, for example, women stricken with breast cancer are often successfully treated and go on to live long lives. But concomitant with this cheering rise in cancer survival is a worrying increase in complaints about cognitive impairment as life goes on. Some cancer survivors have trouble with concentration or fatigue. New research shows this is not just in their minds but, in fact, in their brains.

Daniel H. Silverman of the University of California, Los Angeles, and a cross-disciplinary group of doctors, including U.C.L.A. oncologist Patricia Ganz, used scans to try to identify the brain-based reason for this intellectual deficit. Using positron emission tomography (PET) the researchers tracked both blood flow in the brain as well as the presence of a glucose analogue to examine brain metabolism. They scanned 16 women who had undergone surgery to remove breast tumors as well as chemotherapy in the last decade--including 11 who had been additionally treated with tamoxifen. They were compared with five women who had only undergone surgery and 13 who experienced neither surgery nor chemotherapy.

The researchers examined 40 brain regions as the women performed a word-pairing memory task six times to see how the women--and their brains--differed. The chemotherapy patients showed a significant jump in blood flow to the frontal cortex and cerebellum compared with the controls. "They had to work harder to carry out the same cognitive tasks," Silverman explains. "They have to get a greater increase of activity to be at the same level biochemically." Further, when the researchers scanned the women's brains at rest they found a correlation between those who had the lowest metabolism and those who had the most difficulty performing the task. "That correlation did not exist with people who did not get chemotherapy," he notes.

As a final point of comparison, the doctors looked at how those treated with tamoxifen, which mimics the hormone estrogen, differed from their counterparts. These women showed even more changes to a region of the brain known as the basal ganglia, an executive center believed to link thought and action. The tamoxifen-treated women showed an 8 percent drop on average in metabolism in this region. "It's completely unclear why it got singled out here," Silverman says. But "it does have a different neuropsychological environment than a lot of the other gray matter does."

It remains a mystery how chemotherapy--and tamoxifen--impact the brain, but it is increasingly clear that these treatments may create a cognitive deficit. And, given the small size of this study, it is possible that the researchers were not able to detect other effects that are also occurring, they note in the paper published online on October 5 in Breast Cancer Research and Treatment. But with a new grant from the National Institutes of Health, Ganz and her team plan to embark on a longitudinal study of such patients from diagnosis through treatment and beyond. "Even five to 10 years out from the last dose of chemotherapy, women [who] have received it for their therapy are showing changes in the metabolism of specific regions of their brain and changes in the ability of the brain to modulate itself the way that it needs to when performing mental tasks," Silverman adds. "In effect, these women's brains were working harder than [those of] the control subjects to recall the same information."

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