Most pharmacists are aware that nausea and vomiting, anemia, myelosuppression, neuropathy, weight gain, cardiac toxicity, and fatigue are common side effects suffered by patients undergoing chemotherapy.1 Not as familiar, perhaps, is that many patients, particularly those with breast cancer, also experience mild cognitive impairment. Breast cancer is the most common cancer in women, and women with breast cancer undergoing chemotherapy were the first individuals to notify their physicians about the cognitive changes.
The cause of this impairment has not been elucidated, nor is there a treatment. The incidence, however, has been verified in a growing body of research and in a number of controlled studies.2,3
The condition is pejoratively described as chemo brain. This term is defined as the cognitive dysfunction associated with chemotherapy. Cognitive changes refer to memory and attention loss and other problems that make it difficult for patients to think clearly and carefully.
Approximately 20% to 30% of patients treated with chemotherapeutic drugs may develop cognitive problems. One reason why it is difficult to predict the number accurately is that cognitive impairment may be related to the cancer itself. Some studies have reported that at least half of the participants had memory problems.4
In one study, 3 groups of women (n = 46) were studied. Groups 1 and 2 consisted of patients with stage I or II breast cancer. Group 1 received chemotherapy (cyclophosphamide, methotrexate, and 5-fluorouracil), and group 2 received chemotherapy plus tamoxifen. Group 3 consisted of women with ductal carcinoma in situ who received no chemotherapy or tamoxifen.
Cognitive function was evaluated at 3 time points. Time 1 occurred after surgery and before chemotherapy initiation in groups 1 and 2. Time 1 for group 3 occurred post surgery. Time 2 occurred within 1 week after the conclusion of chemotherapy for groups 1 and 2 and at a comparable time for group 3. Time 3 occurred 1 year after time 2.
Women who received chemotherapy plus tamoxifen exhibited deterioration on measures of visual memory and verbal working memory and reported more memory complaints. Women who received chemotherapy alone also exhibited deteriorations in verbal working memory. Conversely, cognitive-function scores improved in women who received no therapy.
The authors concluded that adjuvant chemotherapy in women with breast cancer can be associated with memory deterioration, and this impairment may persist over time. The addition of tamoxifen may lead to more widespread memory deficits.3
Cancer patients complain about a range of difficulties, from diminished executive function to reduced verbal memory. Many struggle to recall recently acquired information, such as names of people they have met, or to follow overlapping conversations at meetings, or to perform multiple tasks simultaneously. Cognitive impairments may be manifested in situations where distractions occur.3 Chemo brain is frustrating to patients who may suddenly find themselves unable to accomplish tasks they formerly completed with ease.
Most patients who experience chemotherapyrelated cognitive defects find that they return to normal shortly after they finish their regimen. Some, however, experience the effects long after treatment is concluded.5 The difference may be due to the types and doses of the chemotherapy or the genetic influence among patients.
One particular gene being examined is the E4 allele of the apolipoprotein E (APOE) gene. Recent research suggests that the carriers of APOE's E4 allele may have a higher risk of developing long-term cognitive defects after receiving chemotherapy.6 This gene also has been implicated in Alzheimer's disease.7
In the past, doctors assumed that chemo brain was a by-product of other chemotherapy side effects such as anemia, fatigue, or depression. All of these side effects have the potential to cause memory lapses or difficulty in concentrating.8 It is now understood that cognitive impairment is related to physical changes in the brain and unrelated to other side effects.
The results of recent studies indicate that neural damage plays a part in cognitive impairment. In one study, magnetic resonance imaging was performed to explore the regional brain volume difference between breast cancer survivors exposed to adjuvant chemotherapy and those unexposed.9 Breast cancer patients had smaller gray matter and white matter than the controls in the 1-year study.9 Smaller white and gray volumes are associated with larger deficits in attention and learning.
In another study, patients treated for breast cancer with adjuvant chemotherapy were studied with neuropsychological testing and positron emission tomography and were compared with control patients who had never received chemotherapy. Cerebral activation in chemotherapy-treated patients differed most significantly from that in untreated patients in inferior gyrus. Resting metabolism in this area correlated with performance on a short-term memory task previously found to be impaired in the chemotherapy-treated patients. There were specific alterations in the activity of the frontal cortex, cerebellum, and basal ganglia in the breast cancer survivors.2
This study and others like it may help doctors figure out whether specific drugs are causing the problem and how. Such findings could help not only breast cancer patients, but any patient receiving chemotherapy. Breast cancer patients are more likely to be studied in chemo brain research because so many get treatment and live long, healthy lives afterward.10
Currently, no approved treatment exists for any of the chemo brain symptoms. In one study, patients diagnosed with chemotherapy-related fatigue and cognitive impairment were treated experimentally with the central nervous system stimulant dexmethylphenidate for 8 weeks. Compared with those receiving a placebo, patients taking the drug experienced significantly less fatigue and possibly better memory function, although none of the other cognitive functions appeared to improve.11
Being aware of the side effects related to chemotherapy will enhance patient counseling. Breast cancer patients in particular should be informed about possible memory loss or other cognitive changes. A number of factors may be responsible, making it difficult to distinguish chemo brain from the normal effects of treatment. Cognitive problems also can be caused by low blood counts; stress; medication to treat nausea, vomiting, or pain; lingering depression; or hormonal changes. Pharmacists can be of value to patients by suggesting mind exercises (eg, reading, crossword puzzles); keeping a diary of memory problems; taking detailed notes on items to remember; and maintaining a daily routine, such as placing keys in the same place each time.12
Mr. Sherman is president of Sherman Consulting Services Inc.
1. Shapiro CL, Recht A. Side effects of adjuvant treatment of breast cancer. N Engl J Med. 2001;3444:1997-2008.
2. Silverman DHS, Dy CJ, Castellon SA, et al. Altered frontocortical, cerebellar, and basal ganglia activity in adjuvant-treated breast cancer survivors 5-10 years after chemotherapy. Breast Cancer Res Treat. 2006.
3. Bender CM, Sereika SM, Berga SL, et al. Cognitive impairment associated with adjuvant therapy in breast cancer. Psycho-Oncology. 2006;15:422-430.
4. www.mayoclinic.com. Accessed December 8, 2006.
5. Garner K. Can "chemobrain" be mitigated? Dartmouth Medicine. 2005.
6. Ahles T, Saykin A. Cognitive effects of standard-dose chemotherapy in patients with cancer. Cancer Invest. 2001;19:812-820.
7. Huff C. Chemobrain: the hunt for answers. American Psychological Association Online. Available at: http://www.apa.org/monitor/apr05/chemobrain.html. Accessed December 8, 2006.
8. Seeking Solutions to "Chemo-Brain." ACS News Center. American Cancer Society Web site. Available at: http://www.cancer.org/docroot/NWS/content/NWS_2_1x_Seeking_Solutions_to_Chemo-Brain.asp. Accessed December 12, 2006.
9. Inagaki M, Yoshikawa E, Matsuoka Y, et al. Smaller regional volumes of brain gray and white matter demonstrated in breast cancer survivors exposed to adjuvant chemotherapy. Cancer. 2007;109:146-156.
10. "Chemo Brain" Not All in Your Head. ACS News Center. American Cancer Society Web site. Available at: http://www.cancer.org/docroot/NWS/content/NWS_1_1x_Chemo_Brain_Not_All_in_Your_Head.asp. Accessed December 12, 2006.
11. Dexmethylphenidate reduces some symptoms of chemobrain. National Cancer Institute Web site. Available at: www.cancer.gove/clinicaltrials/results/chemobrain. Accessed December 8, 2006.
12. Chemobrain: when cancer treatment disrupts your thinking and memory. MayoClinic Web site. Available at: www.mayoclinic.com/health/cancertreatment/CA00044. Accessed December 8, 2006.
One study linked multiple pregnancies to an increased risk of developing atrial fibrillation later in life, and another investigated the association between premature delivery and cardiovascular disease.
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