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: 7589227
• 负责人: Tim Alan Ahles
• 金额: $ 81.09万
• 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/7589227
• 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; 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; Treatment Protocols; Universities; Vascular Diseases; Visuospatial; Woman; Work; abstracting; advocacy organizations; age group; base; cancer therapy; chemotherapy; 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”）占所有新乳腺癌病例的一半。随着“美国的灰色”，到2030年，被诊断出和接受乳腺癌治疗的老年妇女的绝对数量将几乎翻一番。这些老年患者的治疗指南包括全身治疗，而老年妇女也对化学疗法感兴趣，即使在延长生存方面的少量回报也是如此。但是，全身治疗并非没有副作用，并且许多研究记录了这些药物后的认知能力下降。成像和动物研究证实癌症化疗会影响大脑结构和功能。但是，实际上对老年患者的认知下降知之甚少，因为几乎所有现有的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作用的影响。我们的初步工作表明情况是这种情况，但这从未经过经验测试。这项研究将是第一个大规模，前瞻性，对照研究，以评估老年癌症患者的认知变化。我们使用癌症生存的脆弱性模型来描述系统治疗对认知的影响，在12个月内，认知和生活质量之间的测试关联，并评估APOE多态性是否适度认知结果。我们组建了一个肿瘤学家，老年医生，神经科医生，神经，认知和行为心理学家，以及来自伦巴第综合癌症中心，纪念斯隆凯特癌中心，波士顿大学和Y-ME（国家消费者提倡组织）的消费者。我们将招募325名新诊断为老年乳腺癌患者和相等数量的非癌症朋友对照。参与者将接受基线（系统疗法）神经心理学测试和电话访谈；临床数据将从记录中抽象出来。参与者将在基线后12个月重复认知测​​试和QOL测量。主要结果是在注意力，工作记忆和精神运动速度域中测试的摘要得分的变化。包括四个额外的领域作为次要结果，以评估更广泛的认知功能并检查差异影响：语言；执行功能；学习和记忆；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方案，制定预防性干预措施，告知有关治疗的临床决策以及指导第二代研究。总体而言，鉴于老年人群的预计增长，随着年龄的增长，年龄越来越高的趋势，使用更具侵略性的剂量治疗方案，高生存率和预期寿命的增加，该主题具有较高的研究，临床和公共健康重要性，发病率上升，增长趋势，使用更具侵略性的剂量治疗方案。公共卫生相关性：癌症是美国死亡的主要原因，乳腺癌是我国妇女中第二常见的癌症。老年妇女（65岁及以上的妇女）目前占所有新乳腺癌病例的一半。随着“美国的灰色”和乳腺癌治疗的进展，到2030年，接受乳腺癌治疗和生存的老年妇女人数将几乎翻一番。全身性激素和非荷尔蒙化学疗法的存活率得到了改善，这些方式的使用率在过去的两年中有了实质上的增长。在我们的初步工作中，我们发现，即使对于生存延伸的少量回报，老年女性也对化学疗法感兴趣。然而，在大多数乳腺癌全身治疗研究中都证明了认知障碍，但实际上所有这项研究都是在年轻的人群中进行的。由于衰老本身与认知能力下降有关，因此老年妇女似乎特别容易受到全身治疗的不良认知影响的影响。我们的初步工作强烈表明情况是这种情况，但这从未经过经验测试。这项研究将是评估老年癌症患者认知变化的第一大范围，前瞻性，对照研究，它将为下一代机械，治疗和干预研究提供基础。这些将很重要，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来描述在12个月内对旧乳腺癌患者认知的影响，认知和生活质量（QOL）之间的测试关联，并评估APOE基因中等基因中等认知能力的多态性。为了实现我们的目标，我们组建了一支由肿瘤学家，老年医生，神经科医生，神经和认知心理学家，伦巴第综合癌症中心（LCCC），Sloorial Sloan-Stemorial-kettering癌症中心（MSKCC），Boston University（BU）和National Afficace（BU）（BU）（BU）（National Advoc）（一个国家）（National Advoc）（一个国家）（National Advoc）的多学科团队。该团队将共同努力，前瞻性地招募325例新诊断的已诊断出来自LCCC和MSKCC的较老的乳腺癌病例，该病例是高量的三级推荐中心。 BU将协调认知测试协议。我们将招募相等数量的非癌症朋友控件。我们选择了朋友的控制，因为除了暴露于癌症及其治疗外，它们在大多数方面都与患者相似，因此应激励他们参加。如果没有朋友，我们将招募与年龄，教育，种族和地区（DC/NY）案件相匹配的控件。我们将在进行任何系统治疗之前（或对照组入学时）对基线神经心理学测试进行调查，对女性进行有关主观认知功能，社会心理因素，QOL和日常生活活动（IADLS）的调查。我们将从病历中抽象临床数据。我们将获得血液来测试APOE多态性时的血液；由于这被认为是研究测试，因此不会向参与者提供这些结果。我们进行后续访谈，并在基线评估后12个月重复神经心理学测试；此时间点对应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在注意力，工作记忆和心理运动速度域中测试的摘要得分的变化。在次要分析中，我们检查了其他4个领域的分数变化，以评估更广泛的认知功能并研究差异影响的问题：语言；执行功能；学习和记忆；视觉空间。这项研究的数据将指导未来的干预措施，以更好地选择年龄较大的妇女，这些妇女的益处超过了危害，并开发出一种表明全身治疗的负面影响的方法，从而提高了年龄较大的乳腺癌患者人群不断增长的护理质量。