Cognitive Functioning After Breast Cancer Treatment

描述(申请人提供)：有传闻称，接受乳腺癌辅助化疗的女性患者存在认知障碍，最近对此进行了更严格的研究。可以通过自我报告、标准化的神经心理测试和大脑新陈代谢检查(所有这些都在我们实验室进行了研究)来评估大脑功能。文献表明，接受化疗与神经认知测试表现较差之间存在关系；然而，有认知主诉的患者并不一定测试得很差，他们的主诉往往与抑郁和焦虑症状有关。我们实验室的初步工作表明，与更年期相关的激素变化和乳腺癌的辅助内分泌治疗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大脑功能的潜在机制知之甚少，在这项研究中，我们将通过研究最近完成乳腺癌初级治疗(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)的女性来解决这个问题。我们将通过一个全面的框架来研究内分泌治疗影响大脑功能的潜在机制，该框架除了特定的癌症治疗(化疗、激素治疗)和内源性内分泌暴露(雌激素、皮质醇)之外，还包括体质症状(疲劳、抑郁、焦虑)和免疫变化的作用。在这项纵向的观察性队列研究中，我们提出了以下具体目标：1)通过标准化问卷和神经心理学评估260例乳腺癌患者在初治结束(基线)内分泌治疗开始时和一年后(随访)辅助内分泌治疗对认知功能的影响。2)通过在60名女性的子组中获得正电子发射断层扫描(PET)脑成像，并在接近认知功能基线评估的时间段内进行记忆挑战，来检查认知功能与大脑代谢指标之间的联系，并在一年后进行跟踪评估。3)探讨内分泌辅助治疗影响脑功能的生物-心理-社会机制，观察患者的认知功能和脑代谢的变化，以及与免疫功能、内分泌功能、情绪和症状的关系。报告摘要：乳腺癌是女性最常见的癌症。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。本研究将考察乳腺癌治疗对认知、心理、免疫和内分泌功能的影响，试图了解这些主诉的生物学机制，以便在未来更好地预防或治疗这些主诉。

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.