Regular article Decision-making impairments in breast cancer patients treated with tamoxifen Xingui Chen a,b,1 , Jingjing Li c,d,1 , Juluo Chen b , Dandan Li a , Rong Ye a , Jingjie Zhang e , Chunyan Zhu a , Yanghua Tian b , Kai Wang a,b, ⁎ a Laboratory of Neuropsychology, The First Affiliated Hospital of Anhui Medical University, Hefei, China b Department of Neurology, The First Affiliated Hospital of Anhui Medical University, Hefei, China c Department of Oncology, The Second Affiliated Hospital of Anhui Medical University, Hefei, China d Department of Oncology, The Second Hospital of Zhejiang University College of Medicine, Hangzhou, China e Department of Breast and Thyroid Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, China abstract article info Article history: Received 13 August 2013 Revised 2 July 2014 Accepted 9 July 2014 Available online 15 July 2014 Keywords: Breast cancer Endocrine therapy Iowa Gambling Task Game of Dice Task Tamoxifen 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. © 2014 Elsevier Inc. All rights reserved. Introduction The survival rate of breast cancer patients is increasing with the development of screening and systemic treatment, but complaints of cognitive changes have become common in breast cancer survivors. Initially, researchers studied cognitive changes and found that this phenomenon was associated with chemotherapy treatment (Ahles and Saykin, 2007). However, some studies have recently shown that ad- juvant endocrine therapies which play a key role in hormone-sensitive breast cancer treatment are a potential cause of this cognitive dysfunc- tion (Buwalda and Schagen, 2013; Phillips et al., 2011). Endocrine therapies are most commonly prescribed for patients with hormone-sensitive breast cancer and include selective estrogen re- ceptor modulators (SERMs) and aromatase inhibitors. Among SERMs, tamoxifen (TAM) is frequently prescribed for the treatment of breast cancer in both pre- and post-menopausal women. Aromatase inhibitors are primarily prescribed to post-menopausal women because of their good curative effects and have become increasingly popular in recent years (Burstein et al., 2010). Nevertheless, we felt that TAM was the most plausible choice for our study because it is currently recommend- ed for pre-menopausal breast cancer patients. TAM, a mixed agonist/antagonist, readily crosses the blood brain barrier and binds to estrogen receptors (ERα and ERβ) in the nervous system (McEwen and Alves, 1999). However, it is unknown whether TAM acts as an estrogen agonist or antagonist in the human brain. Estro- gen receptors have been identified in several areas of the brain that are important for cognitive functions, including the prefrontal cortex, hippocampus and amygdala. These brain structures are associated Hormones and Behavior 66 (2014) 449–456 ⁎ Corresponding author at: Laboratory of Neuropsychology, Department of Neurology, The First Affiliated Hospital of Anhui Medical University, Hefei 230032, China. Fax: +86 551 62923704. E-mail address: wangkai1964@126.com (K. Wang). 1 These authors contributed equally to this work. http://dx.doi.org/10.1016/j.yhbeh.2014.07.005 0018-506X/© 2014 Elsevier Inc. All rights reserved. Contents lists available at ScienceDirect Hormones and Behavior journal homepage: www.elsevier.com/locate/yhbeh