Chemo Brain: Hidden Effect of Cancer Treatment

Most pharmacists are awarethat nausea and vomiting,anemia, myelosuppression,neuropathy, weight gain, cardiac toxicity,and fatigue are common sideeffects suffered by patients undergoingchemotherapy.¹ Not as familiar, perhaps,is that many patients, particularlythose with breast cancer, also experiencemild cognitive impairment. Breastcancer is the most common cancer inwomen, and women with breast cancerundergoing chemotherapy werethe first individuals to notify their physiciansabout the cognitive changes.

The cause of this impairment has notbeen elucidated, nor is there a treatment.The incidence, however, hasbeen verified in a growing body ofresearch and in a number of controlledstudies.^2,3

The condition is pejoratively describedas chemo brain. This term isdefined as the cognitive dysfunctionassociated with chemotherapy. Cognitivechanges refer to memory andattention loss and other problems thatmake it difficult for patients to thinkclearly and carefully.

Incidence

Approximately 20% to 30% of patientstreated with chemotherapeuticdrugs may develop cognitive problems.One reason why it is difficult to predictthe number accurately is that cognitiveimpairment may be related to the canceritself. Some studies have reportedthat at least half of the participants hadmemory problems.⁴

In one study, 3 groups of women (n =46) were studied. Groups 1 and 2 consistedof patients with stage I or IIbreast cancer. Group 1 received chemotherapy(cyclophosphamide, methotrexate,and 5-fluorouracil), and group2 received chemotherapy plus tamoxifen.Group 3 consisted of women withductal carcinoma in situ who receivedno chemotherapy or tamoxifen.

Cognitive function was evaluated at3 time points. Time 1 occurred aftersurgery and before chemotherapy initiationin groups 1 and 2. Time 1 forgroup 3 occurred post surgery. Time 2occurred within 1 week after the conclusionof chemotherapy for groups 1and 2 and at a comparable time forgroup 3. Time 3 occurred 1 year aftertime 2.

Women who received chemotherapyplus tamoxifen exhibited deteriorationon measures of visual memory andverbal working memory and reportedmore memory complaints. Womenwho received chemotherapy alone alsoexhibited deteriorations in verbalworking memory. Conversely, cognitive-function scores improved inwomen who received no therapy.

The authors concluded that adjuvantchemotherapy in women with breastcancer can be associated with memorydeterioration, and this impairmentmay persist over time. The addition oftamoxifen may lead to more widespreadmemory deficits.³

Side Effects

Cancer patients complain about arange of difficulties, from diminishedexecutive function to reduced verbalmemory. Many struggle to recallrecently acquired information, such asnames of people they have met, or tofollow overlapping conversationsat meetings, or toperform multiple taskssimultaneously. Cognitiveimpairments may be manifestedin situations wheredistractions occur.³ Chemobrain is frustrating to patientswho may suddenlyfind themselves unable toaccomplish tasks they formerlycompleted with ease.

Most patients who experiencechemotherapyrelatedcognitive defectsfind that they return tonormal shortly after theyfinish their regimen. Some,however, experience theeffects long after treatment is concluded.⁵ The difference may be due to thetypes and doses of the chemotherapyor the genetic influence among patients.

One particular gene being examinedis the E4 allele of the apolipoprotein E(APOE) gene. Recent research suggeststhat the carriers of APOE's E4 allelemay have a higher risk of developinglong-term cognitive defects afterreceiving chemotherapy.⁶ This genealso has been implicated in Alzheimer'sdisease.⁷

Causes

In the past, doctors assumed thatchemo brain was a by-product of otherchemotherapy side effects such as anemia,fatigue, or depression. All of theseside effects have the potential to causememory lapses or difficulty in concentrating.⁸ It is now understood that cognitiveimpairment is related to physicalchanges in the brain and unrelated toother side effects.

The results of recent studies indicatethat neural damage plays a part in cognitiveimpairment. In one study, magneticresonance imaging was performed toexplore the regional brain volume differencebetween breast cancer survivorsexposed to adjuvant chemotherapy andthose unexposed.⁹ Breast cancer patientshad smaller gray matter and whitematter than the controls in the 1-yearstudy.⁹ Smaller white and gray volumesare associated with larger deficits in attentionand learning.

In another study, patients treated forbreast cancer with adjuvant chemotherapywere studied with neuropsychologicaltesting and positron emission tomographyand were compared with controlpatients who had never received chemotherapy.Cerebral activation inchemotherapy-treated patients differedmost significantly from that inuntreated patients in inferior gyrus.Resting metabolism in this area correlatedwith performanceon ashort-term memorytask previouslyfoundto be impairedin the chemotherapy-treatedpatients. Therewere specificalterations inthe activity ofthe frontal cortex, cerebellum, andbasal ganglia in the breast cancer survivors.²

This study and others like it may helpdoctors figure out whether specificdrugs are causing the problem andhow. Such findings could help not onlybreast cancer patients, but any patientreceiving chemotherapy. Breast cancerpatients are more likely to be studiedin chemo brain research because somany get treatment and live long,healthy lives afterward.¹⁰

Treatment

Currently, no approved treatment existsfor any of the chemo brain symptoms.In one study, patients diagnosedwith chemotherapy-related fatigue andcognitive impairment were treatedexperimentally with the central nervoussystem stimulant dexmethylphenidatefor 8 weeks. Compared withthose receiving a placebo, patients takingthe drug experienced significantlyless fatigue and possibly better memoryfunction, although none of the othercognitive functions appeared to improve.¹¹

Final Thoughts

Being aware of the side effects relatedto chemotherapy will enhancepatient counseling. Breast cancerpatients in particular should be informedabout possible memory loss orother cognitive changes. A number offactors may be responsible, making itdifficult to distinguish chemo brainfrom the normal effects of treatment.Cognitive problems also can be causedby low blood counts; stress; medicationto treat nausea, vomiting, or pain;lingering depression; or hormonalchanges. Pharmacists can be of valueto patients by suggesting mind exercises(eg, reading, crossword puzzles);keeping a diary of memory problems;taking detailed notes on items toremember; and maintaining a daily routine,such as placing keys in the sameplace each time.¹²

Mr. Sherman is president of ShermanConsulting Services Inc.

References

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 yearsafter chemotherapy. Breast Cancer Res Treat. 2006.

3. Bender CM, Sereika SM, Berga SL, et al. Cognitive impairment associated withadjuvant 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 patientswith 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 SocietyWeb 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 braingray and white matter demonstrated in breast cancer survivors exposed toadjuvant chemotherapy. Cancer. 2007;109:146-156.

10. "Chemo Brain" Not All in Your Head. ACS News Center. American Cancer SocietyWeb 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 CancerInstitute 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.