Prefrontal cortex abnormalities associated with breast cancer chemotherapy

描述（由申请人提供）：我们的实验室以及其他实验室已经证明了与乳腺癌化疗相关的脑结构和功能异常，最一致的是在前额皮质。前额叶皮层对多任务处理、注意力、处理速度和记忆力等技能至关重要;这些技能在接受过乳腺癌化疗的患者中经常受损。由于在化疗前的患者以及接受放疗和/或激素阻断治疗的患者中也观察到了前额叶皮质的变化，因此化疗对前额叶皮质的具体影响尚不清楚。目前还不清楚为什么一些接受化疗的患者随着时间的推移表现出认知功能的改善，而另一些则没有。这项拟议中的研究将检查50名接受化疗的原发性乳腺癌患者的前额叶皮层结构和功能以及认知状态。这些患者将在整个治疗过程中进行评估，从术前到化疗后12个月。我们将化疗治疗组与50名未接受化疗的患者和50名健康女性进行比较，这些患者均在与化疗治疗组相同的时间间隔进行评估。我们将利用非侵入性神经成像（MRI）方法测量前额叶皮层体积和功能激活，并结合执行功能，记忆，处理速度和注意力的神经心理学测量。我们还将探讨个体结局的可能预测因素，如人口统计学、疾病、精神和治疗因素。增加我们对化疗相关认知障碍的神经生物学机制的理解，可能会改善认知障碍风险最高的患者的识别，并有助于开发这些障碍的治疗方法。 公共卫生相关性：很大一部分接受乳腺癌化疗的妇女将经历长期的脑功能问题，如思维、记忆和注意力，这些问题降低了生活质量，延长了与疾病有关的残疾。这项研究旨在提高我们对乳腺癌化疗期间大脑变化的理解。这项研究与乳腺癌高度相关，乳腺癌是最常见的公共卫生问题之一，影响八分之一的妇女。

DESCRIPTION (provided by applicant): Our laboratory, as well as others, has demonstrated abnormalities in brain structure and function associated with breast cancer chemotherapy, most consistently in the prefrontal cortex. The prefrontal cortex is critical for skills such as multi-tasking, attention, processing speed and memory; skills that are often impaired in patients who have undergone breast cancer chemotherapy. Because prefrontal cortex changes have also been observed in patients prior to chemotherapy treatment as well as in those treated with radiation and/or hormonal blockade, the specific effects of chemotherapy on prefrontal cortex remain unclear. It is also currently unknown why some patients treated with chemotherapy show improvement in cognitive function over time while others do not. The proposed research will examine prefrontal cortex structure and function as well as cognitive status in 50 patients with primary breast cancer scheduled for chemotherapy. These patients will be evaluated across the treatment course, from pre-surgery to 12 months post-chemotherapy. We will compare the chemotherapy-treated group to 50 patients who do not receive chemotherapy and to 50 healthy females who are all assessed at the same time intervals as the chemotherapy-treated group. We will utilize non-invasive neuroimaging (MRI) methods to measure prefrontal cortex volume and functional activation in combination with neuropsychological measures of executive function, memory, processing speed and attention. We will also explore possible predictors of individual outcome such as demographic, disease, psychiatric and treatment factors. Increasing our understanding regarding the neurobiologic mechanisms underlying chemotherapy-related cognitive impairments may improve identification of patients at highest risk for cognitive deficit and aid the development of treatments for these impairments. PUBLIC HEALTH RELEVANCE: A significant proportion of women who receive chemotherapy for breast cancer will experience long- term problems with brain function, such as thinking, memory and attention that reduce quality of life and extend disease-related disability. The proposed study aims to improve our understanding regarding the brain changes that occur during breast cancer chemotherapy. This research is highly relevant to breast cancer, one of the most common public health problems, affecting 1 in 8 women.