Cognitive Functioning After Breast Cancer Treatment

描述（由申请人提供）：在接受乳腺癌辅助化疗的女性中，有认知障碍的轶事报道，最近对此进行了更严格的研究。大脑功能可以通过自我报告、标准化神经心理测试和脑代谢检查来评估（所有这些都在我们的实验室进行了研究）。文献表明，化疗暴露与神经认知测试成绩较差之间存在关系；然而，有认知疾病的患者并不一定测试差，他们的疾病通常与抑郁和焦虑症状有关。我们实验室的初步工作表明，与更年期和乳腺癌辅助内分泌治疗相关的激素变化也会影响化疗对认知功能的影响。关于辅助内分泌治疗影响乳腺癌治疗后脑功能的潜在机制知之甚少，在本研究中，我们将通过研究最近完成原发性乳腺癌治疗（手术、放疗、化疗）并即将开始辅助内分泌治疗（使用他莫昔芬或芳香酶抑制剂）的妇女来解决这个问题。我们将研究内分泌治疗影响脑功能的潜在机制，通过考虑一个全面的框架，包括体质症状（疲劳、抑郁、焦虑）和免疫改变的作用，以及特定的癌症治疗（化疗、激素治疗）和内源性内分泌暴露（雌激素、皮质醇）。在本纵向观察性队列研究中，我们提出以下具体目的：1)通过标准化问卷调查和神经心理学评估260例乳腺癌患者在内分泌治疗初始治疗结束（基线）和1年后（随访）时辅助内分泌治疗对认知功能的影响。2)研究认知功能与脑代谢之间的关系，通过获得正电子发射断层扫描（PET）脑成像，在休息和记忆挑战的情况下，在接近认知功能基线评估的时间范围内，对60名女性进行测试，并在一年后进行随访评估。3)通过观察认知功能和脑代谢的变化及其与免疫和内分泌功能、情绪和症状的关系，探讨辅助内分泌治疗影响脑功能的生物心理社会机制。总结：乳腺癌是女性中最常见的癌症。在接受乳腺癌治疗后，一些女性抱怨难以集中注意力和思考。这项研究将检查乳腺癌治疗对认知、心理、免疫和内分泌功能的影响，试图了解这些疾病的生物学机制，以便将来更好地预防或治疗它们。

DESCRIPTION (provided by applicant): Cognitive complaints have been anecdotally reported among women receiving adjuvant chemotherapy for breast cancer, and recently this has been subjected to more rigorous study. Cerebral functioning can be assessed by self-report, standardized neuropsychological testing, and through examination of brain metabolism (all of which have been studied in our laboratory). The literature suggests a relationship between chemotherapy exposure and poorer performance on neurocognitive testing; however, patients with cognitive complaints do not necessarily test poorly and their complaints are often associated with symptoms of depression and anxiety. Preliminary work in our laboratory suggests that hormonal changes associated with menopause and adjuvant endocrine therapy for breast cancer also influence the effects of chemotherapy on cognitive functioning. Little is known about the potential mechanisms by which adjuvant endocrine therapy influences cerebral functioning after breast cancer treatment, and in this study we will address this question by studying women who have recently completed their primary breast cancer treatments (surgery, radiation, chemotherapy) and who are about to initiate adjuvant endocrine therapy (with tamoxifen or aromatase inhibitors). We will examine the potential mechanisms by which endocrine therapy affects cerebral functioning, by consideration of a comprehensive framework that includes the role of constitutional symptoms (fatigue, depression, anxiety), and immune alterations, in addition to specific cancer treatments (chemotherapy, hormonal treatments), and endogenous endocrine exposures (estrogen, cortisol). In this longitudinal, observational cohort study, we propose the following specific aims: 1)To evaluate the effects of adjuvant endocrine therapy on cognitive functioning through standardized questionnaires and neuropsychological assessments in 260 breast cancer patients at the end of primary treatment (baseline) when endocrine treatment is initiated, and one year later (follow-up). 2)To examine the association between cognitive functioning and measures of cerebral metabolism by obtaining positron emission tomography (PET) brain imaging, at rest and with a memory challenge, in close temporal proximity to the baseline assessment of cognitive functioning in a subset of 60 women, with a follow-up assessment one year later. 3)To explore the biopsychosocial mechanisms by which adjuvant endocrine therapy influences cerebral functioning by examining changes in cognitive functioning and brain metabolism, and their relationship to immune and endocrine function, mood and symptoms between the baseline and follow-up assessment one year later. Lay summary: Breast cancer is the most common cancer in women. After treatments for breast cancer, some women complain of difficulty in concentrating and thinking. This study will examine the effects of breast cancer treatments on cognitive, psychological, immune and endocrine function to try to understand the biological mechanisms of these complaints so that they may be better prevented or treated in the future.