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'Chemo Brain' in Cancer Survivors Is Real: Study

By Alan Mozes

HealthDay Reporter

THURSDAY, Oct. 5 (HealthDay News) -- " Chemo brain, " characterized by

chronic problems with memory and attention, afflicts a sizeable

minority of cancer survivors.

Now, researchers say the condition may be linked to brain metabolism

and blood flow changes that can endure for more than a decade.

The new study, published in the Oct. 5 online edition of Breast Cancer

Research and Treatment, should help refute the view that chemo brain

is just a figment of patients' imaginations.

" Many women who have had chemo for breast cancer are suffering from

cognitive problems for many years after their chemo is finished, and

this is the first direct examination of the brain that identifies

long-term, if not permanent, changes in brain metabolism related to

those cognitive problems, " said study lead author Dr. H.S.

Silverman, of the department of molecular and medical pharmacology at

the University of California's Geffen School of Medicine in Los

Angeles.

Although chemo brain has been spotted among survivors of other forms

of cancer, such as lymphoma, Silverman's group focused on breast

cancer patients because the disease is the second-leading cancer

killer of American women after lung cancer.

Each year, more than 211,000 American women are diagnosed with breast

cancer, the researchers noted, and anywhere from approximately 25

percent to 80 percent of those who undergo chemotherapy complain of

later onset of cognitive difficulties.

Silverman stressed, however, that not every breast cancer patient who

undergoes chemo suffers from chemo brain, and that many of those who

do experience only mild symptoms.

" The impact tends to be relatively subtle, " Silverman said. " These are

not basic losses of cognition that are going to be noticed when doing

easy things. It's more a question of being unable to maintain

attention and concentrate when trying to accomplish demanding and

high-functioning tasks. "

Nevertheless, for some of those who experience this cognitive

disruption, the impact can be debilitating. That's why Silverman and

his colleagues looked for underlying mechanisms to better understand

the condition.

Using positron emission tomography -- commonly known as PET -- the

UCLA team scanned the brains of 21 former breast cancer patients who

had had tumors surgically removed between five and 10 years prior to

this study.

Sixteen of the women had undergone chemotherapy, while the remaining

five had had surgery alone. Scans were also conducted for 13 women of

similar age and backgrounds with no history of breast cancer or

chemotherapy.

The researchers observed brain blood-flow patterns as participants

engaged in short-term memory exercises lasting about 10 minutes. They

also measured brain metabolism after the exercise.

Silverman's team found that the post-chemo patients experienced

relatively large blood flow " spikes " to certain parts of the brain

when performing the mental tasks. This group also executed the tasks

13 percent less well than the non-chemo and non-cancer groups.

As well, former chemotherapy recipients showed relatively low brain

metabolism rates in the frontal cortex after the tasks were completed,

the researchers noted.

Participants who had undergone both chemotherapy and hormonal

treatments also showed about an eight percent drop in their resting

metabolism in a region of the brain called the basal ganglia.

The basal ganglia is known to function as a bridge between thought and

action, the researchers noted.

Putting all the facts together, Silverman's team said the task-related

blood flow jumps in the brains of former chemotherapy recipients

indicated increased brain activity. That may mean that the chemo group

were starting from a neurological disadvantage -- working harder (and

with less success) to complete the tasks than those who had never

undergone such treatment.

" Chemo-brain symptoms are the single biggest impediment to the quality

of life of long-term breast cancer survivors who are getting chemo at

earlier and earlier stages and living longer, or even to full life

expectancy, " noted Silverman. " So, of course, this is discouraging

news if you're trying to do something for the affected patients after

the fact. "

" But on the other hand, " he noted, " these findings could ultimately be

very encouraging in terms of trying to prevent this, because you could

perhaps identify patterns of brain metabolism that could help steer

individual patients toward therapy regimens that would be least

harmful for them, or to terminate therapies before they cause

permanent brain damage. "

Dr. Claudine Isaacs, director of the clinical breast cancer program at

town University, said the study was interesting but

inconclusive.

" These are very provocative findings, and I think this is the way we

need to go in terms of utilizing imaging studies to better understand

the problem, " she said. " But to know what all this means is another

thing. "

" The problem is that this is so multi-factorial, " cautioned Isaacs.

" There are so many things that go into this -- age-related influences,

menopause -- and it's very difficult to tease out the different

parts. "

" It is also true, " she added, " that other studies in this area have

shown that a relative minority of patients are affected by this

phenomenon, and that in substantial numbers, the problems resolve over

time among those who are. So, the situation is not necessarily

forever. "

More information

To learn more about chemo brain, visit the American Cancer Society.

SOURCES: H.S. Silverman, M.D., Ph.D., department of molecular

and medical pharmacology, University of California, Geffen

School of Medicine, Los Angeles; Claudine Isaacs, M.D., associate

professor, medicine, and director, clinical breast cancer program,

town University, Washington D.C.; Oct. 5, 2006, online edition,

Breast Cancer Research and Treatment.

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Breast Cancer Res Treat. 2007 Jul;103(3):303-11. Epub 2006 Sep 29.

Altered frontocortical, cerebellar, and basal ganglia activity in

adjuvant-treated breast cancer survivors 5-10 years after

chemotherapy.

Silverman DH, Dy CJ, Castellon SA, Lai J, Pio BS, Abraham L, Waddell

K, sen L, Phelps ME, Ganz PA.

Department of Molecular and Medical Pharmacology, University of

California, Geffen School of Medicine, Los Angeles, CA, USA.

Purpose To explore the relationship of regional cerebral blood

flow and metabolism with cognitive function and past exposure to

chemotherapy for breast cancer. Patients and methods Subjects treated

for breast cancer with adjuvant chemotherapy remotely (5-10 years

previously) were studied with neuropsychologic testing and positron

emission tomography (PET), and were compared with control subjects who

had never received chemotherapy. [O-15] water PET scans was acquired

during performance of control and memory-related tasks to evaluate

cognition-related cerebral blood flow, and [F-18] fluorodeoxyglucose

(FDG) PET scans were acquired to evaluate resting cerebral metabolism.

PET scans were analyzed by statistical parametric mapping and region

of interest methods of analysis. Results During performance of a

short-term recall task, modulation of cerebral blood flow in specific

regions of frontal cortex and cerebellum was significantly altered in

chemotherapy-treated subjects. Cerebral activation in

chemotherapy-treated subjects differed most significantly from

untreated subjects in inferior frontal gyrus, and resting metabolism

in this area correlated with performance on a short-term memory task

previously found to be particularly impaired in chemotherapy-treated

subjects. In examining drug-class specific effects, metabolism of the

basal ganglia was significantly decreased in tamoxifen +

chemotherapy-treated patients compared with chemotherapy-only breast

cancer subjects or with subjects who had not received chemotherapy,

while chemotherapy alone was not associated with decreased basal

ganglia activity relative to untreated subjects. Conclusion Specific

alterations in activity of frontal cortex, cerebellum, and basal

ganglia in breast cancer survivors were documented by functional

neuroimaging 5-10 years after completion of chemotherapy.

PMID: 17009108 [PubMed - in process]