OLDER BREAST CANCER PATIENTS: RISK FOR COGNITIVE DECLINE

老年乳腺癌患者：认知能力下降的风险

• 批准号: 7849788
• 负责人: Tim Alan Ahles
• 金额: $ 83.31万
• 依托单位: GEORGETOWN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-06-01 至 2014-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7849788
• 关键词: Accounting; Activities of Daily Living; Address; Adverse effects; Affect; Aftercare; Age; Aged, 80 and over; Aging; Aging-Related Process; Alleles; Alzheimer' s Disease; Alzheimer' s disease risk; Americas; Animals; Apolipoprotein E; Area; Attention; Behavioral; Blood; Body mass index; Boston; Brain; Breast Cancer Treatment; Cancer Control; Cancer Patient; Cancer Survivorship; Categories; Cause of Death; Chemotherapy-Oncologic Procedure; Clinical; Clinical Data; Cognition; Cognitive; Cognitive deficits; Communities; Comprehensive Cancer Center; Consumer Advocacy; Country; Data; Decision Making; Diagnosis; Diffuse; Disease; Dose; Education; Elderly; Enrollment; Exposure to; Fatigue; Female; Foundations; Frequencies; Friends; Fright; Future; General Population; Generations; Genes; Genetic Polymorphism; Gray unit of radiation dose; Growth; Guidelines; High Prevalence; Hormonal; Image; Impaired cognition; In Situ; Incidence; Institute of Medicine (U.S.); Intervention; Intervention Studies; Interview; Investigation; Knowledge; Language; Lead; Learning; Life Expectancy; Link; Literature; Magnetic Resonance Imaging; Malignant Neoplasms; Measures; Medical Records; Medicine; Memorial Sloan-Kettering Cancer Center; Memory; Modality; Modeling; Moods; National Cancer Advisory Board; Neurologist; Neuropsychological Tests; Newly Diagnosed; Older Population; Oncologist; Outcome; Participant; Patients; Pharmaceutical Preparations; Pharmacogenetics; Population; Population Study; President' s Cancer Panel; Preventive Intervention; Protocols documentation; Psychologist; Psychosocial Factor; Public Health; Quality of Care; Quality of life; Race; Recommendation; Records; Recruitment Activity; Regimen; Reporting; Research; Research Priority; Risk; Risk Factors; Scientist; Short-Term Memory; Source; Speed; Structure; Surveys; Survival Rate; Symptoms; System; Systemic Therapy; Telephone Interviews; Testing; Time; Toxic effect; Translating; Universities; Vascular Diseases; Visuospatial; Woman; Work; abstracting; advocacy organizations; age group; base; cancer therapy; chemotherapy; clinical decision-making; cognitive change; cognitive function; cohort; design; executive function; experience; follow-up; genetic profiling; genetic risk factor; gray matter; hormone therapy; human old age (65+); improved; interest; malignant breast neoplasm; next generation; normal aging; older patient; older women; prevent; primary outcome; prospective; public health relevance; secondary outcome; trend; white matter

DESCRIPTION (provided by applicant): 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. PUBLIC HEALTH RELEVANCE: Cancer is the leading cause of death in the US and breast cancer is the second most common cancer among women in our country. Older women (women 65 and older) presently account for nearly half of all new cases of breast cancer. With the "graying of America" and advances in treatment for breast cancer, the absolute number of older women undergoing breast cancer treatment and surviving their disease will almost double by the year 2030. Systemic hormonal and non-hormonal chemotherapy is credited with improvements in survival, and rates of use of these modalities have increased substantially over the past two decades. In our preliminary work, we have found that older women are interested in chemotherapy even for small returns in survival extension. However, cognitive impairment has been demonstrated in most studies of breast cancer systemic treatments, but virtually all of this research has been conducted in younger populations. Since aging itself is associated with cognitive declines, it seems very likely that older women are particularly vulnerable to the adverse cognitive effects of systemic therapy; our preliminary work strongly 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 and it will provide the basis for the next generation of mechanistic, treatment and intervention studies. These will be important since data from younger patients cannot be directly translated into the older population. We will use the vulnerability model of cancer survivorship to prospectively describe systemic therapy effects on cognition in older breast cancer patients over a 12 month period, test associations between cognition and quality of life (QOL) and to evaluate whether polymorphisms in the APOE gene moderate cognitive outcomes. To achieve our objectives, we have assembled a multi-disciplinary team of oncologists, geriatricians, neurologists, neuro- and cognitive psychologists, behavioral scientists and consumers from Lombardi Comprehensive Cancer Center (LCCC), Memorial Sloan-Kettering Cancer Center (MSKCC), Boston University (BU) and Y-Me (a national consumer advocacy organization). This team will work together to prospectively enroll 325 newly diagnosed older breast cancer cases from LCCC and MSKCC, tertiary referral centers with high volumes. BU will coordinate cognitive testing protocols. We will recruit an equal number of non-cancer friend controls. We have chosen friend controls since they will be similar to patients in most ways except for exposure to cancer and its treatments and they should be motivated to participate. If friends are not available, we will recruit controls matched to cases on age, education, race, and area (DC/NY). We will administer baseline neuropsychological testing prior to any systemic treatment (or at enrollment for controls), survey women about subjective cognitive function, psychosocial factors, QOL and activities of daily living (IADLS). We will abstract clinical data from medical records. We will obtain blood to test for APOE polymorphisms at enrollment; these results will not be provided to participants since this is considered a research test). We conduct follow-up interviews and repeat the neuropsychological testing 12 months after baseline assessment; this time point corresponds to 3-6 months post-treatment among women who receive chemotherapy. Our primary cognitive outcome will be change in summary score on tests in the Attention, Working Memory, and Psychomotor Speed Domain. In secondary analyses we examine changes in scores on 4 additional domains to assess broader cognitive function and examine questions of differential impact: Language; Executive Functioning; Learning and Memory; Visual-spatial. Data from this study will guide future interventions to better select older women for whom the benefits of systemic therapy outweigh the harms and to develop approaches to mitigate negative consequences of systemic treatment when it is indicated, improving the quality of care for the growing population of older breast cancer patients.

描述（由申请人提供）：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“美国的老龄化”，到 2030 年，被诊断出并接受乳腺癌治疗的老年女性的绝对数量将几乎翻倍。这些老年患者的治疗指南包括全身治疗，而老年女性对化疗感兴趣，因为即使是延长生存期的回报很小。但全身治疗并非没有副作用，许多研究都记录了接受这些药物后认知能力下降。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，实际上对老年患者认知能力下降的情况知之甚少，因为几乎所有现有研究都是在年轻患者中进行的。由于衰老本身与认知能力下降有关，因此老年患者可能特别容易受到全身治疗的不良认知影响。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评估老年癌症患者认知变化的大规模、前瞻性、对照研究。我们使用癌症生存的脆弱性模型来描述 12 个月内系统治疗对认知的影响，测试认知与生活质量之间的关联，并评估 APOE 多态性是否会调节认知结果。我们组建了一支由肿瘤学家、老年病学家、神经学家、神经、认知和行为心理学家以及来自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（全国消费者权益组织）的消费者组成的团队。我们将招募 325 名新诊断的老年乳腺癌患者和同等数量的非癌症朋友对照。参与者将接受基线（系统治疗前）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总分的变化。另外四个领域被纳入作为次要结果，以评估更广泛的认知功能并检查差异影响：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女性设计适当的治疗方案、制定预防干预措施、为治疗的临床决策提供信息并指导第二代研究。总体而言，考虑到老年人口的预计增长、发病率随着年龄的增长而上升、老年患者越来越多地使用全身治疗的趋势、使用更积极的给药方案、高生存率和预期寿命的增加，这一主题具有很高的研究、临床和公共卫生重要性。公共卫生相关性：癌症是美国的首要死因，乳腺癌是我国女性第二常见的癌症。目前，老年女性（65 岁及以上的女性）占所有新发乳腺癌病例的近一半。随着“美国的老龄化”和乳腺癌治疗的进步，到 2030 年，接受乳腺癌治疗并幸存的老年妇女的绝对数量将几乎翻倍。全身激素和非激素化疗被认为可以改善生存率，并且这些疗法的使用率在过去二十年中大幅增加。在我们的初步工作中，我们发现老年女性对化疗感兴趣，即使是为了延长生存期带来的微小回报。然而，大多数乳腺癌全身治疗研究都证明了认知障碍，但实际上所有这些研究都是在年轻人中进行的。由于衰老本身与认知能力下降有关，因此老年女性似乎特别容易受到全身治疗的不良认知影响；我们的初步工作强烈表明情况确实如此，但从未经过实证检验。这项研究将是第一个评估老年癌症患者认知变化的大规模、前瞻性、对照研究，并将为下一代机制、治疗和干预研究提供基础。这些很重要，因为年轻患者的数据不能直接转化为老年人群。我们将使用癌症生存的脆弱性模型前瞻性地描述 12 个月内系统治疗对老年乳腺癌患者认知的影响，测试认知与生活质量 (QOL) 之间的关联，并评估 APOE 基因的多态性是否会调节认知结果。为了实现我们的目标，我们组建了一支多学科团队，由来自隆巴迪综合癌症中心 (LCCC)、纪念斯隆-凯特琳癌症中心 (MSKCC)、波士顿大学 (BU) 和 Y-Me（全国消费者倡导组织）的肿瘤学家、老年病学家、神经学家、神经和认知心理学家、行为科学家和消费者组成。该团队将共同努力，前瞻性地从 LCCC 和 MSKCC 这两个三级转诊中心招募 325 例新诊断的老年乳腺癌病例。 BU 将协调认知测试协议。我们将招募同等数量的非癌症朋友对照。我们选择了朋友对照，因为除了接触癌症及其治疗之外，他们在大多数方面与患者相似，并且应该激励他们参与。如果没有朋友，我们将招募与年龄、教育程度、种族和地区（华盛顿/纽约）情况相匹配的对照。我们将在任何系统治疗之前（或在对照入组时）进行基线神经心理学测试，调查女性的主观认知功能、心理社会因素、生活质量和日常生活活动 (IADLS)。我们将从医疗记录中提取临床数据。我们将在入组时抽取血液进行APOE多态性检测；这些结果不会提供给参与者，因为这被视为研究测试）。我们在基线评估后 12 个月进行后续访谈并重复神经心理学测试；该时间点相当于接受化疗的女性治疗后 3-6 个月。我们的主要认知结果将是注意力、工作记忆和精神运动速度领域测试的总结分数的变化。在二次分析中，我们检查另外 4 个领域的分数变化，以评估更广泛的认知功能并检查不同影响的问题：语言；执行职能；学习与记忆；视觉空间。这项研究的数据将指导未来的干预措施，以更好地选择全身治疗利大于弊的老年女性，并开发出减轻全身治疗负面后果的方法，从而提高对不断增长的老年乳腺癌患者群体的护理质量。