Altered frontocortical, cerebellar, and basal ganglia activity in adjuvant-treated breast cancer survivors 5–10 years after chemotherapy
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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.
KeywordsPositron emission tomography Brain Breast cancer Tamoxifen Adjuvant chemotherapy FDG Cerebral blood flow
- 2.Ganz PA (2002) What outcomes matter to patients: a physician-researcher point of view. MedCare 40:III11-III19Google Scholar
- 6.Ahles TA, Saykin AJ, Furstenberg CT, Cole B, Mott LA, Skalla IK, Whedon MB, Bivens S, Mitchell T, Greenberg ER, Silberfarb PM (2002) Neuropsychologic impact of standard-dose systemic chemotherapy in long- term survivors of breast cancer and lymphoma. J Clin Oncol 20:485–493PubMedCrossRefGoogle Scholar
- 10.Tchen N, Juffs HG, Downie FP, Qi-Long Y, Hu H, Chemerynsky I, Clemons M, Crump M, Goss PE, Warr D, Tweedale ME, Tannock IF (2003) Cognitive function, fatigue, and menopausal symptoms in women receiving adjuvant chemotherapy for breast cancer. Journal of Clinical Oncology, 21:4175–4183PubMedCrossRefGoogle Scholar
- 17.Silverman DHS, Alavi A (2005) PET imaging in the assessment of normal and impaired cognitive function. Radiologic Clin North Am Saunders/Elsevier, Philadelphia, 43:67–77Google Scholar
- 18.Lai J, Dy CJ, Pio BS, Ganz PA, Castellon SA, Abraham L, Waddell K, Phelps ME, Bookheimer SY, Silverman DHS (2005) Anterior cingulate and temporal lobe regions associated with congruence of memory recall to mood. J Nucl Med 46(5, abstr. suppl):no. 29Google Scholar
- 20.Talairach J, Tournoux P (1988) Co-planar stereotaxic atlas of the human brain. 3-dimensional proportional system: An approach to cerebral imaging. New York: ThiemeGoogle Scholar
- 21.Friston K, Ashburner J, Heather J, et al (2003) Statistical Parametric Mapping (SPM2). Available at www.fil.ion.ucl.ac.uk/spm (The Wellcome Department of Cognitive Neurology, University College London, London)Google Scholar
- 22.Partridge AH, Burstein HJ, Winer EP (2001) Side effects of chemotherapy and combined chemohormonal therapy in women with early-stage breast cancer. J Natl Cancer Inst Monogr 135–142Google Scholar
- 23.Ganz PA (2001a) Impact of tamoxifen adjuvant therapy on symptoms, functioning, and quality of life. J Natl Cancer Inst Monogr 130–134Google Scholar
- 28.Ganz PA, Rowland JH, Desmond K, Meyerowitz BE, Wyatt GE (1998a) Life after breast cancer: understanding women’s health-related quality of life and sexual functioning. J Clin Oncol 16:501–514Google Scholar
- 31.Ganz PA, Rowland JH, Meyerowitz BE, Desmond KA (1998b) Impact of different adjuvant therapy strategies on quality of life in breast cancer survivors. Recent Results Cancer Res 152:396–411Google Scholar
- 40.Schmamann JD, ed: The cerebellum and cognition. Academic Press, San Diego, 1997Google Scholar
- 41.Silverman DHS and Melega WP (2004) Molecular imaging of biological processes with PET: evaluating biologic bases of cerebral function. In PET: Molecular Imaging and Its Biological Applications ME Phelps, ed., Springer-Verlag, New York, pp. 509–583Google Scholar
- 45.Komenich PKD, Lane M, Dickey RP, Stone SC (1978) Gonadal hormones and cognitive performance. Physiological Psychology 6:115–120Google Scholar
- 54.Shumaker SA, Legault C, Rapp SR, Thal L, Wallace RB, Ockene JK, Hendrix SL, Jones III BN, Assaf AR, Jackson RD, Morley Kotchen J, Wassertheil-Smoller S, Wactawski-Wende J (2003) Estrogen Plus Progestin and the Incidence of Dementia and Mild Cognitive Impairment in Postmenopausal Women: The Women’s Health Initiative Memory Study: A Randomized Controlled Trial. JAMA 289:2651PubMedCrossRefGoogle Scholar
- 55.Rapp SR, Espeland MA, Shumaker SA, Henderson VW, Brunner RL, Manson JE, Gass MLS, Stefanick ML, Lane DS, Hays J, Johnson KC, Coker LH, Dailey M, Bowen D (2003) Effect of Estrogen Plus Progestin on Global Cognitive Function in Postmenopausal Women: The Women’s Health Initiative Memory Study: A Randomized Controlled Trial. JAMA 289:2663PubMedCrossRefGoogle Scholar
- 63.Holmes C, El-Okl M, Williams AL, Cunningham C, Wilcockson D, Perry VH (2003) Systemic infection, interleukin 1beta, and cognitive decline in Alzheimer’s disease. J Neurol Neurosurg Psychiatry Jun;74(6):788–9Google Scholar
- 68.Blair JR, Spreen O: Predicting pre-morbid IQ (1989) a revision of the National Adult Reading Test. The Clinical Neuropsychologist, 3:129–136Google Scholar