Cognitive Function and Breast Cancer: Genomics and Disease Characteristics

描述(由申请人提供)：乳腺癌幸存者目前是美国最大的癌症幸存者群体，有290万女性。乳腺癌幸存者经历的最常见和最有问题的现象之一是认知功能的变化或认知下降，其定义是认知功能的一个或多个领域的下降或丧失，包括注意力、学习、记忆、精神运动速度、心理灵活性、执行功能和视觉空间能力。虽然多种因素可能预测患有乳腺癌并接受治疗的女性认知功能较差，但我们假设乳腺癌的疾病相关因素可能是认知功能下降的主要原因。我们的总体目标是更好地了解癌症和治疗相关认知能力下降的生物学基础。这项研究的具体目的是：1)研究乳腺癌临床病理肿瘤特征与乳腺癌患者认知功能的关系；2)探讨乳腺癌临床生物学评价基因的DNA变异与乳腺癌患者认知功能下降的易感性或保护作用；3)探讨乳腺癌临床病理肿瘤特征与乳腺癌临床生物学评价基因DNA变异对认知功能的影响。利用从一项正在进行的大型纵向研究“女性使用阿那曲唑相关的认知损害”研究(R01CA107408)收集的生物谱学和认知功能数据，拟议的研究将重点关注接受各种化疗和/或激素治疗方案的早期乳腺癌绝经后妇女，并与年龄和教育程度相匹配的健康妇女进行比较。回归模型、候选基因关联和缓和分析(统计交互作用)将用于探索辅助化疗和/或激素治疗开始之前和之后一段时间的认知功能。这项初步研究的发现将为一系列研究奠定基础，以确定临床相关的生物标志物和 认知功能衰退的乳腺癌幸存者的新疗法。

DESCRIPTION (provided by applicant): Breast cancer survivors currently comprise the largest group of cancer survivors in the United States at 2.9 million women. One of the most common and problematic phenomena experienced by breast cancer survivors is changes in cognitive function or cognitive decline, defined as a decrease or loss in one or more domains of cognitive function including attention, learning, memory, psychomotor speed, mental flexibility, executive function, and visuospatial ability. While multiple factors potentially predict poorer cognitive function in women with and receiving treatment for breast cancer, we hypothesize that disease-related factors of breast cancer may be a major contributor to cognitive decline. Our overall goal is to gain a better understanding of the biological foundations of cancer- and treatment-related cognitive decline. The specific aims of the proposed research are: 1) To investigate the relationship between clinicopathologic tumor features of breast cancer and cognitive function in women with breast cancer, 2) To explore DNA variation in genes used to clinically evaluate the biology of breast cancer for association with susceptibility to or protectin from cognitive decline in women with breast cancer, and 3) To explore interactions between clinicopathologic tumor features of breast cancer and DNA variation in genes used to clinically evaluate the biology of breast cancer on cognitive function. Using biospecimens and cognitive function data collected from a large, ongoing longitudinal study, the "Cognitive Impairment Related to Anastrozole Use in Women" Study (R01CA107408), the proposed study will focus on postmenopausal women with early stage breast cancer receiving various chemotherapy and/or hormonal therapy treatment regimens in comparison to healthy age- and education-matched women. Regression modeling, candidate gene association, and moderation analyses (statistical interactions) will be used to explore cognitive function prior to and over time following the initiation of adjuvant chemotherapy and/or hormonal therapy. The findings from this preliminary study will lay the foundation for a line of research to identify clinically relevant biomarkers and novel therapies for survivors of breast cancer experiencing cognitive decline.