OLDER BREAST CANCER PATIENTS: RISK FOR COGNITIVE DECLINE

摘要 65 岁及以上的女性（“老年女性”）占所有新发乳腺癌病例的近一半。随着 “美国老龄化”被诊断并接受乳腺癌治疗的老年妇女的绝对数量 到 2030 年将几乎翻倍。这些老年患者的治疗指南包括全身治疗 老年女性对化疗感兴趣，即使是延长生存期的小回报。但系统性的 治疗并非没有副作用，许多研究都记录了接受治疗后认知能力下降 这些代理。影像学和动物研究证实癌症化疗会影响大脑结构和 功能。然而，实际上我们对老年患者的认知能力下降知之甚少，因为几乎所有的 现有的研究是在年轻患者中进行的。由于衰老本身与认知能力有关 下降，老年患者可能特别容易受到全身性认知障碍的不利影响 治疗。我们的初步工作表明情况确实如此，但从未经过实证检验。 这项研究将是第一个大规模、前瞻性、对照调查，以评估认知变化 老年癌症患者。我们使用癌症生存的脆弱性模型来描述系统治疗 12 个月内对认知的影响，测试认知与生活质量之间的关联，并 评估 APOE 多态性是否调节认知结果。我们组建了一支团队 肿瘤学家、老年病学家、神经学家、神经、认知和行为心理学家以及消费者 隆巴迪综合癌症中心、纪念斯隆-凯特琳癌症中心、波士顿大学和 Y- Me（全国消费者权益倡导组织）。我们将招募 325 名新诊断的老年乳腺癌患者 患者和同等数量的非癌症朋友对照。参与者将接受基线（系统前 治疗）神经心理学测试和电话访谈；临床数据将从记录中提取。 参与者将在基线后 12 个月重复认知测​​试和生活质量测量。主要结果是 注意力、工作记忆和精神运动速度领域测试的总分发生变化。 四个额外的领域被纳入作为次要结果，以评估更广泛的认知功能和 检查不同的影响：语言；执行职能；学习与记忆；视觉空间。 这项研究的结果将有助于为老年妇女设计适当的治疗方案，开发 预防干预措施，为临床治疗决策提供信息，并指导第二代 研究。总体而言，鉴于预计的增长，该主题具有很高的研究、临床和公共卫生重要性 在老年人群中，发病率随着年龄的增长而上升，有增加使用全身治疗的趋势 对于老年患者，使用更积极的给药方案可以提高生存率并延长预期寿命。

ABSTRACT Women 65 and older ("older women") account for nearly half of all new cases of breast cancer. With the "graying of America" the absolute number of older women diagnosed and undergoing breast cancer treatment will almost double by the year 2030. Treatment guidelines for these older patients include systemic therapy and older women are interested in chemotherapy for even small returns in survival extension. But systemic therapy is not without side effects, and numerous studies have documented cognitive decline after receipt of these agents. Imaging and animal studies confirm that cancer chemotherapy affects brain structure and function. However, very little is actually known about cognitive decline in older patients, because virtually all of the existing research has been conducted in younger patients. Since aging itself is associated with cognitive decline, older patients are likely to be particularly vulnerable to the adverse cognitive effects of systemic therapy. Our preliminary work suggests that this is the case, but this has never been empirically tested. This study will be the first large scale, prospective, controlled investigation to evaluate cognitive changes in older cancer patients. We use the vulnerability model of cancer survivorship to describe systemic therapy effects on cognition over a 12 month period, test associations between cognition and quality of life and to evaluate whether APOE polymorphisms moderate cognitive outcomes. We have assembled a team of oncologists, geriatricians, neurologists, neuro-, cognitive and behavioral psychologists and consumers from Lombardi Comprehensive Cancer Center, Memorial Sloan-Kettering Cancer Center, Boston University and Y- Me (a national consumer advocacy organization). We will enroll 325 newly diagnosed older breast cancer patients and an equal number of non-cancer friend controls. Participants will undergo baseline (pre-systemic therapy) neuropsychological testing and telephone interviews; clinical data will be abstracted from records. Participants will repeat cognitive testing and QOL measures 12 months after baseline. The primary outcome is change in the summary score on tests in the Attention, Working Memory, and Psychomotor Speed Domain. Four additional domains are included as secondary outcomes to assess broader cognitive function and examine differential impact: Language; Executive Functioning; Learning and Memory; Visuospatial. The results of this study will contribute to designing appropriate regimens for older women, developing preventive interventions, informing clinical decision-making about treatment, and guiding second generation studies. Overall, this topic has high research, clinical and public health importance, given the projected growth in the older population, rising incidence with advancing age, trends towards increasing use of systemic therapy in older patients, use of more aggressive dosing regimens, high survival rates, and increasing life expectancy.