A longitudinal, nationally representative study of cognition-related effects of breast cancer and its treatment

关于乳腺癌及其治疗的认知相关影响的纵向、全国代表性研究

• 批准号: 10709517
• 负责人: Ann B Nattinger
• 金额: $ 34.97万
• 依托单位: MEDICAL COLLEGE OF WISCONSIN
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-23 至 2026-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10709517
• 关键词: Address; Adjuvant; Adjuvant Therapy; Adverse effects; Affect; Aftercare; Age; Alzheimer' s Disease; Androgens; Area; Aromatase; Aromatase Inhibitors; Autopsy; Benefits and Risks; Brain; Breast Cancer Patient; Breast Cancer Treatment; Breast Cancer survivor; Cancer Survivor; Cancer Survivorship; Caring; Cessation of life; Characteristics; Clinical; Clinical Trials; Cognition; Cognitive; Cognitive aging; Communities; Cross-Sectional Studies; Data; Data Sources; Diagnosis; Disease; Education; Effectiveness; Eligibility Determination; Enzymes; Estrogen Antagonists; Estrogen Receptors; Estrogens; Exhibits; Exposure to; Future; Goals; Guidelines; Health and Retirement Study; Hormones; Human; Impaired cognition; Intervention; Late Effects; Life; Literature; Longitudinal Studies; Longitudinal Surveys; Malignant Neoplasms; Measures; Medical; Medicare; Neuropsychology; Operative Surgical Procedures; Parameter Estimation; Patient Care; Patients; Performance; Persons; Pharmacologic Substance; Population; Population Heterogeneity; Postmenopause; Predisposition; Prospective, cohort study; Quality of life; Recurrent disease; Research Design; Time; Tissues; Treatment outcome; Woman; Work; breast cancer diagnosis; cancer diagnosis; cancer therapy; cancer-related cognitive impairment; chemotherapy; cognitive function; cognitive testing; comparison control; deprivation; functional improvement; health data; hormone receptor-positive; hormone therapy; inhibitor therapy; innovation; interest; malignant breast neoplasm; neural; novel; premalignant; sociodemographics

ABSTRACT More breast cancer patients are treated with anti-estrogen agents, such as aromatase inhibitors (AIs), than with any treatment other than surgery. Due to their effectiveness, recent guidelines for postmenopausal women advise extending AI therapy to 10-years duration. Therefore, exposure to AIs among the more than 3.5 million breast cancer survivors will soon increase. A major concern of breast cancer survivors is therapy-induced cognitive dysfunction. About 75% of women suffer cancer-related cognitive impairment during chemotherapy treatment, which persists for months to years. There are theoretical and empirical reasons to believe that cognitive impairment may also occur with estrogen deprivation. Surprisingly, there are few empirical human studies of AI effects on cognition; none with cognition measured pre-cancer. Leveraging 18 years of data from the Health and Retirement Studies―a nationally-representative, longitudinal survey augmented by Medicare medical and pharmaceutical claims, we propose a longitudinal study designed to: (1) Characterize breast cancer survivors’ cognitive functioning post-initiation of adjuvant AI therapy over a 60-month period using a validated neuropsychological measure and compare their performance to those of (i) women with incident breast cancer who did not receive AI therapy and (ii) non-cancer controls. Cross-sectional analyses corresponding to roughly one-, three-, and five years post-AI therapy initiation will provide estimates of early and late effects of AIs; (2) Contrast the longitudinal trajectory of cognitive functioning preceding and following cancer diagnosis and treatment among women treated with an AI to those of (i) cancer survivors who did not receive AI therapy and (ii) cancer-free controls, over an 18-year span. We anticipate a gradual decline in cognitive functioning among cancer-free women over the study period. The AI group, however, is expected to exhibit a steeper downward slope after AI initiation, indicating an adverse AI effect on cognition above and beyond normal cognitive aging; and (3) Quantify the tradeoff between overall and disease-free life years and cognitive functioning among women with incident breast cancer undergoing different adjuvant therapies. Using findings from Aim 2 combined with parameter estimates from analyses of time to disease recurrence and time to death, we will calculate overall and disease-free life years by cognitive functioning for various scenarios of patients’ sociodemographic characteristics and cancer treatment(s). Results from these analyses will provide rigorous evidence regarding the potentially adverse effects of AI exposure on cognition that may serve as the basis for clinical interventions. They will also generate population-level estimates of survival and cognitive decline attributable to AI and other cancer-treatments (beyond normal cognitive aging) that could be used to better inform patients about “real world” tradeoffs of different breast cancer treatments. Finally, our results will be important for all interested in the challenges of better understanding cancer-related cognitive impairment and improving the functioning and quality of life of the large and growing number of breast cancer survivors.

摘要 更多的乳腺癌患者接受抗雌激素药物的治疗，如芳香酶抑制剂(Ais)。 接受除手术以外的任何治疗。由于其有效性，最近针对绝经后妇女的指南 建议将人工智能治疗延长至10年。因此，对认可机构的风险敞口在350多万人中 乳腺癌幸存者很快就会增加。乳腺癌幸存者的一个主要担忧是治疗诱导 认知功能障碍。约75%的女性在化疗期间遭受癌症相关的认知障碍 治疗，持续数月至数年。有理论和经验上的理由相信 缺乏雌激素也可能导致认知障碍。令人惊讶的是，很少有经验性的人类 人工智能对认知影响的研究；没有一项研究是在癌症前测量认知能力的。利用18年来来自 健康和退休研究-一项具有全国代表性的纵向调查，由联邦医疗保险扩大 医学和药物方面的声明，我们建议进行一项纵向研究，旨在：(1)确定乳房的特征 癌症幸存者在开始人工智能辅助治疗60个月后的认知功能 经过验证的神经心理测量，并将她们的表现与(I)有事件的女性的表现进行比较 未接受人工智能治疗的乳腺癌患者和(Ii)非癌症对照组。横断面分析 与人工智能治疗开始后大约一年、三年和五年相对应，将提供早期 (2)对比认知功能前后的纵向轨迹 接受人工智能治疗的妇女的癌症诊断和治疗与(I)未接受人工智能治疗的癌症幸存者的癌症诊断和治疗 接受人工智能治疗和(Ii)非癌症对照，跨度为18年。我们预计将逐步下降 在研究期间，非癌症女性的认知功能。然而，预计人工智能集团将 在人工智能启动后表现出更陡峭的下坡，表明人工智能对上述认知和 超越正常的认知老化；以及(3)量化总体寿命和无疾病寿命之间的权衡，以及 接受不同辅助治疗的乳腺癌复发妇女的认知功能。vbl.使用 目标2的发现与疾病复发时间和时间分析的参数估计相结合 到死亡，我们将根据认知功能计算总体和无疾病寿命，针对不同情况 患者的社会人口学特征与癌症治疗(S)。这些分析的结果将提供 关于人工智能暴露对认知的潜在不利影响的严格证据可能作为 为临床干预提供依据。他们还将产生人口水平的生存和认知估计 下降可归因于人工智能和其他癌症治疗方法(超出正常认知老化)，可用于 更好地让患者了解不同乳腺癌治疗方法的“现实世界”权衡。最后，我们的结果将 对于所有对更好地理解癌症相关认知障碍的挑战感兴趣的人来说，这一点很重要 并改善数量庞大且不断增加的乳腺癌幸存者的功能和生活质量。