Article

Is basic research providing answers if adjuvant anti-estrogen treatment of breast cancer can induce cognitive impairment?

Behavioral Physiology, University of Groningen, Nijenborgh 7, 9747 AG Groningen, the Netherlands. Electronic address: .
Life sciences (Impact Factor: 2.3). 01/2013; DOI: 10.1016/j.lfs.2012.12.012
Source: PubMed

ABSTRACT Adjuvant treatment of cancer by chemotherapy is associated with cognitive impairment in part of the cancer survivors. Breast cancer patient are frequently also receiving endocrine therapy with selective estrogen receptor modulators (SERM's) and/or aromatase inhibitors (AI's) to suppress the growth of estradiol sensitive breast tumors. Estrogens are well-known, however, to target brain areas involved in the regulation of cognitive behavior. In this review clinical and basic preclinical research is reviewed on the actions of estradiol, SERM's and AI's on brain and cognitive functioning to see if endocrine therapy potentially induces cognitive impairment and in that respect may contribute to the detrimental effects of chemotherapy on cognitive performance in breast cancer patients. Although many clinical studies may be underpowered to detect changes in cognitive function, current basic and clinical reports suggest that there is little evidence that AI's may have a lasting detrimental effect on cognitive performance in breast cancer patients. The clinical data on SERM's are not conclusive, but some studies do suggest that tamoxifen administration may form a risk for cognitive functioning particularly in older women. An explanation may come from basic preclinical research which indicates that tamoxifen often acts agonistic in the absence of estradiol but antagonistic in the presence of endogenous estradiol. It could be hypothesized that the negative effects of tamoxifen in older women is related to the so-called window of opportunity for estrogen. Administration of SERM's beyond this so-called window of opportunity may not be effective or might even have detrimental effects similar to estradiol.

0 Followers
 · 
74 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: Objective: Endocrine therapy is widely used-often for many years-in women with breast cancer. Yet little is known about cognitive functioning after long-term use of tamoxifen. We examine cognitive sequelae, approximately 3 years after diagnosis, in postmenopausal women with breast cancer who were treated with adjuvant tamoxifen. Methods: Data from participants who underwent surgical operation with or without radiotherapy, participants who received adjuvant tamoxifen, and healthy controls were collected. Neuropsychological tests were administered, and participants completed questionnaires on health-related quality of life (Quality of Life Questionnaire Core 30 and Breast Cancer-Specific Quality-of-Life Questionnaire), menopausal symptoms (Functional Assessment of Cancer Therapy-Breast endocrine symptom subscale), and anxiety and depression (Hopkins Symptom Checklist). Results: In total, 107 women participated (adjuvant tamoxifen group, n = 20; surgical operation/radiotherapy group, n = 43; healthy control group, n = 44). Women in the adjuvant tamoxifen group had received tamoxifen for a mean (SD) of 31.5 (18.6) months (range, 15-79 mo) and performed worse on verbal memory than the surgical operation/radiotherapy group (P < 0.05) and the healthy control group (P < 0.05). Participants in the adjuvant tamoxifen group performed worse on measures of fluency than healthy controls (P < 0.05). Furthermore, women in the adjuvant tamoxifen group reported worse cognitive functioning (P < 0.05) than women in the surgical operation/radiotherapy group or the healthy control group. Conclusions: Our results provide insights into cognitive functioning in women who receive long-term adjuvant tamoxifen treatment. By adding the surgical operation/radiotherapy group, we could control for the mental and physical influences of the diagnosis and treatment of breast cancer. Cognitive domains that rely on verbal abilities (verbal memory and fluency) seem to be at risk for deterioration after treatment with tamoxifen.
    Menopause 06/2014; 22(1). DOI:10.1097/GME.0000000000000271 · 2.81 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The potentially detrimental effects of cancer and related treatments on cognitive functioning are emerging as a key focus of cancer survivorship research. Many patients with central nervous system (CNS) or non-CNS tumours develop cognitive problems during the course of their disease that can result in diminished functional independence. We review the state of knowledge on the cognitive functioning of patients with primary and secondary brain tumours at diagnosis, during and after therapy, and discuss current initiatives to diminish cognitive decline in these patients. Similarly, attention is paid to the cognitive sequelae of cancer and cancer therapies in patients without CNS disease. Disease and treatment effects on cognition are discussed, as well as current insights into the neural substrates and the mechanisms underlying cognitive dysfunction in these patients. In addition, rehabilitation strategies for patients with non-CNS disease confronted with cognitive dysfunction are described. Special attention is given to knowledge gaps in the area of cancer and cognition, in CNS and non-CNS diseases. Finally, we point to the important role for cooperative groups to include cognitive endpoints in clinical trials in order to accelerate our understanding and treatment of cognitive dysfunction related to cancer and cancer therapies.
    EJC Supplements 06/2014; 12(1). DOI:10.1016/j.ejcsup.2014.03.003 · 9.39 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Purpose This report examines cognitive complaints and neuropsychological (NP) testing outcomes in patients with early-stage breast cancer after the initiation of endocrine therapy (ET) to determine whether this therapy plays any role in post-treatment cognitive complaints. Patients and Methods One hundred seventy-three participants from the Mind Body Study (MBS) observational cohort provided data from self-report questionnaires and NP testing obtained at enrollment (T1, before initiation of ET), and 6 months later (T2). Bivariate analyses compared demographic and treatment variables, cognitive complaints, depressive symptoms, quality of life, and NP functioning between those who received ET versus not. Multivariable linear regression models examined predictors of cognitive complaints at T2, including selected demographic variables, depressive symptoms, ET use, and other medical variables, along with NP domains that were identified in bivariate analyses. Results Seventy percent of the 173 MBS participants initiated ET, evenly distributed between tamoxifen or aromatase inhibitors. ET-treated participants reported significantly increased language and communication (LC) cognitive complaints at T2 (P = .003), but no significant differences in NP test performance. Multivariable regression on LC at T2 found higher LC complaints significantly associated with T1 LC score (P < .001), ET at T2 (P = .004), interaction between ET and past hormone therapy (HT) (P < .001), and diminished improvement in NP psychomotor function (P = .05). Depressive symptoms were not significant (P = .10). Conclusion Higher LC complaints are significantly associated with ET 6 months after starting treatment and reflect diminished improvements in some NP tests. Past HT is a significant predictor of higher LC complaints after initiation of ET. (C) 2014 by American Society of Clinical Oncology
    Journal of Clinical Oncology 09/2014; 32(31). DOI:10.1200/JCO.2014.56.1662 · 17.88 Impact Factor