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290万妇女。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或认知下降的变化，定义为认知功能的一个或多个领域的减少或丧失，包括注意力，学习，记忆，心理速度，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和接受乳腺癌治疗的女性的认知功能较差，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因素。我们的总体目标是更好地了解癌症和治疗相关认知下降的生物学基础。拟议研究的具体目标是：1）研究乳腺癌临床病理肿瘤特征与乳腺癌女性认知功能之间的关系，2）探索用于临床评估乳腺癌生物学的基因中的DNA变异与乳腺癌女性认知功能下降的易感性或保护性的相关性，3）探讨乳腺癌临床病理肿瘤特征与用于临床评估乳腺癌生物学对认知功能的影响的基因中的DNA变异之间的相互作用。使用从一项大型、正在进行的纵向研究“女性使用阿那曲唑相关的认知障碍”研究（R 01 CA 107408）中收集的生物标本和认知功能数据，拟定的研究将重点关注接受各种化疗和/或激素治疗方案的绝经后早期乳腺癌女性，并与年龄和教育程度匹配的健康女性进行比较。将使用回归建模、候选基因关联和适度分析（统计学相互作用）来探索辅助化疗和/或激素治疗开始之前和之后的认知功能。这项初步研究的结果将为一系列研究奠定基础，以确定临床相关的生物标志物， 乳腺癌幸存者认知能力下降的新疗法。

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.