Decision-making impairments in breast cancer patients treated with tamoxifen
Abstract
The selective estrogen receptor modulator tamoxifen (TAM) is most commonly prescribed for patients with hormone-sensitive breast cancer. Although TAM can bind to estrogen receptors in the nervous system, it is unknown whether it acts as an estrogen agonist or antagonist in the human brain. Several studies have reported the negative effects of TAM on cognitive function; however, its effects on decision-making function have not been previously explored. The present study aimed to investigate the decision-making function under ambiguity and risk in breast cancer patients treated with TAM. Participants included breast cancer patients taking TAM (TAM, n=47) and breast cancer patients not taking TAM (non-TAM, n=45) as well as their matched healthy controls (HC, n=50). All participants were given the Iowa Gambling Task (IGT) to assess their decision-making under conditions involving ambiguity, the Game of Dice Task (GDT) to assess their decision-making under conditions involving risk, and a battery of neuropsychological tests. Our results indicated that patients in the TAM group were significantly impaired as assessed by both the IGT and GDT and performed significantly worse on some aspects of various tasks involving memory and information processing. Furthermore, we found that decreased performance on verbal memory testing significantly correlated with IGT performance, and executive dysfunction was associated with poor GDT performance in breast cancer patients undergoing TAM treatment. This study demonstrates that breast cancer patients taking TAM have several decision-making impairments. These findings may support the idea that TAM resulting in cognitive changes plays an antagonistic role in the areas of the brain where estrogen receptors are present, including the prefrontal cortex, hippocampus and amygdala.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
A subpopulation of TAM-treated patients experience cognitive disturbances such as confusion, deterioration of verbal memory, and executive dysfunction (often called "TAM brain fog").
“TAM, via unknown mechanisms, induces cognitive impairment in humans.”
From Tamoxifen induces cellular stress in the nervous system by inhibiting cholesterol synthesis (2015) · cites this paper as [2]
Cites
Studies of interference in serial verbal reactions
Stroop, J. R. (1935) · Journal of Experimental Psychology · doi:10.1037/h0054651 · Cited by 18,622 · see citing works
Insensitivity to future consequences following damage to human prefrontal cortex
Bechara, A., Damasio, A. R., Damasio, H., & Anderson, S. W. (1994) · Cognition · doi:10.1016/0010-0277(94)90018-3 · Cited by 6,128 · see citing works
Deciding advantageously before knowing the advantageous strategy
Bechara, A., Damasio, H., Tranel, D., & Damasio, A. R. (1997) · Science · doi:10.1126/science.275.5304.1293 · Cited by 3,547 · see citing works
Lipsey, M. W., & Wilson, D. B. (1993) · American Psychologist · doi:10.1037/0003-066x.48.12.1181 · Cited by 2,033 · see citing works
Different contributions of the human amygdala and ventromedial prefrontal cortex to decision-making
Bechara, A., Damasio, H., Damasio, A. R., & Lee, G. P. (1999) · The Journal of Neuroscience · doi:10.1523/jneurosci.19-13-05473.1999 · Cited by 2,001 · see citing works
Executive Function and the Frontal Lobes: A Meta-Analytic Review
Alvarez, J. A., & Emory, E. (2006) · Neuropsychology Review · doi:10.1007/s11065-006-9002-x · Cited by 1,981 · see citing works
By Carrot or by Stick: Cognitive Reinforcement Learning in Parkinsonism
Frank, M. J., Seeberger, L. C., & O'Reilly, R. C. (2004) · Science · doi:10.1126/science.1102941 · Cited by 1,964 · see citing works
Estrogen Actions in the Central Nervous System
McEwen, B. S., & Alves, S. E. (1999) · Endocrine Reviews · doi:10.1210/edrv.20.3.0365 · Cited by 1,483 · see citing works
Neural systems responding to degrees of uncertainty in human decision-making
Hsu, M., Bhatt, M., Adolphs, R., Tranel, D., & Camerer, C. F. (2005) · Science · doi:10.1126/science.1115327 · Cited by 1,411 · see citing works
Bechara, A. (2004) · Brain and Cognition · doi:10.1016/j.bandc.2003.04.001 · Cited by 1,172 · see citing works
Hold Your Horses: Impulsivity, Deep Brain Stimulation, and Medication in Parkinsonism
Frank, M. J., Samanta, J., Moustafa, A. A., & Sherman, S. J. (2007) · Science · doi:10.1126/science.1146157 · Cited by 1,116 · see citing works
Anterior cingulate cortex and conflict detection: an update of theory and data
Carter, C. S., & van Veen, V. (2007) · Cognitive, Affective, & Behavioral Neuroscience · doi:10.3758/cabn.7.4.367 · Cited by 1,056 · see citing works
Reward-motivated learning: mesolimbic activation precedes memory formation
Adcock, R. A., Thangavel, A., Whitfield-Gabrieli, S., Knutson, B., & Gabrieli, J. D. E. (2006) · Neuron · doi:10.1016/j.neuron.2006.03.036 · Cited by 977 · see citing works
Candidate mechanisms for chemotherapy-induced cognitive changes
Ahles, T. A., & Saykin, A. J. (2007) · Nature reviews. Cancer · doi:10.1038/nrc2073 · Cited by 924 · see citing works
The revised Piper Fatigue Scale: psychometric evaluation in women with breast cancer.
Piper, B. F., Dibble, S. L., Dodd, M. J., Weiss, M. C., Slaughter, R. E., & Paul, S. M. (1998) · PubMed · Cited by 838 · see citing works
Burstein, H. J., Prestrud, A. A., Seidenfeld, J., Anderson, H., Buchholz, T. A., Davidson, N. E., Gelmon, K. A., Giordano, S. H., Hudis, C. A., Malin, J. L., et al. (2010) · Journal of Clinical Oncology · doi:10.1200/jco.2009.26.3756 · Cited by 794 · see citing works
Effects of estrogen on memory function in surgically menopausal women
Phillips, S. M. (1992) · Psychoneuroendocrinology · doi:10.1016/0306-4530(92)90007-t · Cited by 737 · see citing works
Wittmann, B. C., Schott, B. H., Guderian, S., Frey, J. U., Heinze, H.-J., & Düzel, E. (2005) · Neuron · doi:10.1016/j.neuron.2005.01.010 · Cited by 698 · see citing works
Variations in sex-related cognitive abilities across the menstrual cycle
Hampson, E. (1990) · Brain and Cognition · doi:10.1016/0278-2626(90)90058-v · Cited by 571 · see citing works
Brand, M., Recknor, E. C., Fabian Grabenhorst, B., & Bechara, A. (2006) · Journal of Clinical and Experimental Neuropsychology · doi:10.1080/13803390500507196 · Cited by 553 · see citing works
Neuropsychological correlates of decision-making in ambiguous and risky situations
Brand, M., Labudda, K., & Markowitsch, H. J. (2006) · Neural Networks · doi:10.1016/j.neunet.2006.03.001 · Cited by 488 · see citing works
Brand, M., Fujiwara, E., Borsutzky, S., Kalbe, E., Kessler, J., & Markowitsch, H. J. (2005) · Neuropsychology · doi:10.1037/0894-4105.19.3.267 · Cited by 473 · see citing works
Novel Mechanisms of Estrogen Action in the Brain: New Players in an Old Story
Toran‐Allerand, C. D., Singh, M., & Sétáló, G. (1999) · Frontiers in Neuroendocrinology · doi:10.1006/frne.1999.0177 · Cited by 427 · see citing works
Kløve, H. (1963) · Medical Clinics of North America · doi:10.1016/s0025-7125(16)33515-5 · Cited by 411 · see citing works
Silverman, D. H. S., Dy, C. J., Castellon, S. A., Lai, J., Pio, B. S., Abraham, L., Waddell, K., Petersen, L., Phelps, M. E., & Ganz, P. A. (2006) · Breast Cancer Research and Treatment · doi:10.1007/s10549-006-9380-z · Cited by 395 · see citing works
Estrogen actions in the central nervous system
McMillan, P. J., & Dorsa, D. M. (1999) · Current Opinion in Endocrinology & Diabetes · doi:10.1097/00060793-199902000-00006 · Cited by 391 · see citing works
Cerebral hyporesponsiveness and cognitive impairment 10 years after chemotherapy for breast cancer
de Ruiter, M. B., Reneman, L., Boogerd, W. J., Veltman, D. J., van Dam, F. S. A. M., Nederveen, A. J., Boven, E., & Schagen, S. B. (2010) · Human Brain Mapping · doi:10.1002/hbm.21102 · Cited by 306 · see citing works
Fan, H. M., Tchen, N., Yi, Q., Chemerynsky, I., Downie, F. P., Sabate, K., & Tannock, I. F. (2005) · Journal of Clinical Oncology · doi:10.1200/jco.2005.01.6550 · Cited by 280 · see citing works
Vardy, J. L., Rourke, S. B., & Tannock, I. F. (2007) · Journal of Clinical Oncology · doi:10.1200/jco.2006.08.1604 · Cited by 270 · see citing works
Schilder, C. M. T., Seynaeve, C., Beex, L. V. A. M., Boogerd, W. J., Linn, S. C., Gundy, C. M., Huizenga, H. M., Nortier, J. W. R., van de Velde, C. J., van Dam, F. S. A. M., et al. (2010) · Journal of Clinical Oncology · doi:10.1200/jco.2008.21.3553 · Cited by 270 · see citing works
The role of the striatum and hippocampus in planning: A PET activation study in Parkinson's disease
Dagher, A. (2001) · Brain · doi:10.1093/brain/124.5.1020 · Cited by 259 · see citing works
Hormone replacement therapy for cognitive function in postmenopausal women
Lethaby, A. E., Hogervorst, E., Richards, M., Yesufu-Udechuku, A., & Yaffe, K. S. (2008) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd003122.pub2 · Cited by 214 · see citing works
Estrogen- and tamoxifen-associated effects on brain structure and function
Eberling, J. L., Wu, C. C., Tong-Turnbeaugh, R., & Jagust, W. (2003) · NeuroImage · doi:10.1016/j.neuroimage.2003.08.037 · Cited by 211 · see citing works
Euteneuer, F., Schaefer, F., Stuermer, R., Boucsein, W., Timmermann, L., Barbe, M. T., Ebersbach, G., Otto, J., Kessler, J., & Kalbe, E. (2009) · Neuropsychologia · doi:10.1016/j.neuropsychologia.2009.06.014 · Cited by 165 · see citing works
Wolf, O. T., Kudielka, B. M., Hellhammer, D. H., Törber, S., McEwen, B. S., & Kirschbaum, C. (1999) · Psychoneuroendocrinology · doi:10.1016/s0306-4530(99)00025-6 · Cited by 147 · see citing works
The effects of hormone therapy on cognition in breast cancer
Shilling, V. M., Jenkins, V. A., Fallowfield, L. J., & Howell, A. (2003) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2003.07.001 · Cited by 136 · see citing works
Kobayakawa, M., Koyama, S., Mimura, M., & Kawamura, M. (2007) · Movement Disorders · doi:10.1002/mds.21865 · Cited by 135 · see citing works
Agnès Lacreuse, A., Wilson, M. E., & Herndon, J. G. (2002) · Neurobiology of Aging · doi:10.1016/s0197-4580(02)00002-7 · Cited by 130 · see citing works
Schilder, C. M. T., Eggens, P. C., Seynaeve, C., et al. (2008) · Acta Oncologica · doi:10.1080/02841860802314738 · Cited by 119 · see citing works
Radon in homes--a possible cause of lung cancer.
Edling, C., Kling, H., & Axelson, O. (1984) · Scandinavian Journal of Work Environment & Health · doi:10.5271/sjweh.2366 · Cited by 108 · see citing works
Cohen, M. X., Elger, C. E., & Weber, B. (2007) · NeuroImage · doi:10.1016/j.neuroimage.2007.10.004 · Cited by 106 · see citing works
Decision making in patients with temporal lobe epilepsy
Labudda, K., Frigge, K., Horstmann, S., Aengenendt, J., Woermann, F. G., Ebner, A., Markowitsch, H. J., & Brand, M. (2008) · Neuropsychologia · doi:10.1016/j.neuropsychologia.2008.08.014 · Cited by 103 · see citing works
Grigorova, M., Sherwin, B. B., & Tulandi, T. (2006) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2006.05.004 · Cited by 94 · see citing works
Epperson, C. N., Amin, Z., Ruparel, K., Gur, R. C., & Loughead, J. (2011) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2011.07.007 · Cited by 94 · see citing works
Palmer, J. L., Trotter, T., Joy, A. A., & Carlson, L. E. (2008) · Journal of Cancer Survivorship · doi:10.1007/s11764-008-0070-1 · Cited by 89 · see citing works
Focal basal ganglia lesions are associated with impairments in reward-based reversal learning
Bellebaum, C., Koch, B., Schwarz, M., & Daum, I. (2008) · Brain · doi:10.1093/brain/awn011 · Cited by 88 · see citing works
So, W. K. W., Dodgson, J. E., & Tai, J. W. M. (2003) · Cancer Nursing · doi:10.1097/00002820-200306000-00006 · Cited by 77 · see citing works
Cognitive functioning after cancer treatment
Phillips, K. M., Jim, H., Small, B. J., Laronga, C., Andrykowski, M. A., & Jacobsen, P. B. (2011) · Cancer · doi:10.1002/cncr.26432 · Cited by 74 · see citing works
Hormone replacement therapy for cognitive function in postmenopausal women
Hogervorst, E., Yaffe, K. S., Richards, M., & Huppert, F. A. (2002) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd003122 · Cited by 71 · see citing works
The Modified Fuld Verbal Fluency Test: A Validation Study in Hong Kong
Chiu, H. F. K., Chan, C. K. Y., Lam, L. C. W., Ng, K.-C., Li, S.-W., Wong, M. M., & Chan, W. F. (1997) · The Journals of Gerontology Series B · doi:10.1093/geronb/52b.5.p247 · Cited by 67 · see citing works
Effects of estrogens on cognition and brain morphology: Involvement of the cerebellum
Ghidoni, R., Boccardi, M., Benussi, L., Testa, C., Villa, A., Pievani, M., Gigola, L., Sabattoli, F., Barbiero, L., Frisoni, G. B., et al. (2005) · Maturitas · doi:10.1016/j.maturitas.2005.11.002 · Cited by 46 · see citing works
Cognitive functioning in premenstrual syndrome
Morgan, M., JRAPKIN, A., DELIA, L., Reading, A. E., & Goldman, L. K. (1996) · Obstetrics and Gynecology · doi:10.1016/s0029-7844(96)00362-6 · Cited by 46 · see citing works
Lezak (1984) · PubMed · Cited by 46 · see citing works
Do aromatase inhibitors have adverse effects on cognitive function?
Phillips, K. A., Ribi, K., & Fisher, R. (2011) · Breast Cancer Research · doi:10.1186/bcr2806 · Cited by 45 · see citing works
Walker, E. A., Foley, J. J., Clark‐Vetri, R., & Raffa, R. B. (2011) · Psychopharmacology · doi:10.1007/s00213-011-2310-8 · Cited by 44 · see citing works
Buwalda, B., & Schagen, S. B. (2013) · Life Sciences · doi:10.1016/j.lfs.2012.12.012 · Cited by 43 · cited 1× · see citing works
“However, some studies have recently shown that adjuvant endocrine therapies which play a key role in hormone-sensitive breast cancer treatment are a potential cause of this cognitive dysfunction (Buwalda and Schagen, 2013; Phillips et al., 2011).”
Effects of Hormone Replacement Therapy and Aging on Cognition: Evidence for Executive Dysfunction
Wegesin, D. J., & Stern, Y. (2006) · Aging Neuropsychology and Cognition · doi:10.1080/13825580600802893 · Cited by 30 · see citing works
Decision-making impairments in patients with Wilson's disease
Ma, H., Xin-yi, L., Han, Y., Zhang, F., Ye, R., Yu, F., Han, Y., Schiebener, J., & Wang, K. (2013) · Journal of Clinical and Experimental Neuropsychology · doi:10.1080/13803395.2013.789486 · Cited by 13 · see citing works
Self-citationCognitive deficits are usually mild in patients with breast cancer after chemotherapy
Barton, M. K. (2012) · CA A Cancer Journal for Clinicians · doi:10.3322/caac.21164 · Cited by 10 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Tamoxifen induces cellular stress in the nervous system by inhibiting cholesterol synthesis
Denk, F., Ramer, L. M., Erskine, E. L. K. S., Nassar, M. A., Bogdanov, Y., Signore, M., Wood, J. N., McMahon, S. B., & Ramer, M. S. (2015) · Acta Neuropathologica Communications · doi:10.1186/s40478-015-0255-6 · Cited by 44 · see citing works
- Authors
- Chen, X., Li, J., Chen, J., Li, D., Ye, R., Zhang, J., Zhu, C., Tian, Y., & Wang, K.
- Affiliations
- First Affiliated Hospital of Anhui Medical University (CN)
- Second Affiliated Hospital of Anhui Medical University (CN)
- Corresponding author
- Wang, Kai
- Venue
- Hormones and Behavior
- Publisher
- Elsevier BV
- Published
- 2014-07
- Volume
- 66
- Issue
- 2
- Pages
- 449-456
- ISSN
- 0018-506X (ISSN-L)
- OpenAlex
- W2036342544
- Cited by
- 44
- References
- 59
- Citations by year
- 2026: 4 · 2025: 2 · 2024: 5 · 2023: 5 · 2022: 2 · 2021: 3 · 2020: 3 · 2019: 2 · 2018: 2 · 2017: 7 · 2016: 5 · 2015: 4
- FWCI
- 4.25
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Hormones and Behavior (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (91232717, 81300944, 31300925, 81070877, 31100812)
- National Basic Research Program of China (2011CB707805)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Cancer-related cognitive impairment studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Keywords
- tamoxifen, breast cancer, decision-making, cognitive impairment, ambiguity, risk, Iowa Gambling Task, Game of Dice Task, verbal memory, executive dysfunction, estrogen receptor antagonism, selective estrogen receptor modulators, neuropsychological outcomes
- MeSH terms
- Adult, Aged, Breast Neoplasms, Decision Making, Female, Gambling, Humans, Memory, Middle Aged, Neuropsychological Tests, Psychomotor Performance, Risk-Taking, Tamoxifen, Antineoplastic Agents, Hormonal, Feedback, Psychological, Executive Function
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
