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.

抽象的 接受芳香酶抑制剂 (AI) 等抗雌激素药物治疗的乳腺癌患者多于接受抗雌激素药物治疗的乳腺癌患者。 由于其有效性，最近针对绝经后妇女的指南。 建议将 AI 治疗期限延长至 10 年，因此，超过 350 万人接触过 AI。 乳腺癌幸存者将很快增加 乳腺癌幸存者的一个主要问题是治疗引起的。 大约 75% 的女性在化疗期间出现与癌症相关的认知障碍。 治疗持续数月至数年 有理论和经验理由相信 令人惊讶的是，认知障碍也可能因雌激素剥夺而发生。 人工智能对认知影响的研究；没有利用 18 年的数据来测量癌症前的认知。 健康与退休研究——一项由医疗保险增强的全国代表性纵向调查 医学和药物声明，我们提出一项纵向研究，旨在： (1) 描述乳房特征 癌症幸存者在 60 个月的时间里开始辅助 AI 治疗后的认知功能 验证神经心理学测量并将其表现与 (i) 发生事件的女性的表现进行比较 未接受 AI 治疗的乳腺癌患者和 (ii) 非癌症对照。 对应于人工智能治疗开始后大约一年、三年和五年，将提供早期的估计 和人工智能的后期影响；（2）对比前后认知功能的纵向轨迹 接受 AI 治疗的女性与 (i) 未接受 AI 治疗的癌症幸存者之间的癌症诊断和治疗 在 18 年的时间里，接受 AI 治疗和 (ii) 无癌症控制的患者数量预计会逐渐下降。 然而，人工智能组预计在研究期间，无癌症女性的认知功能会有所改善。 人工智能启动后表现出更陡峭的下降斜率，表明人工智能对上述认知产生不利影响 超出正常的认知衰老；(3) 量化总生命年和无病生命年之间的权衡； 接受不同辅助治疗的乳腺癌女性的认知功能。 目标 2 的结果与疾病复发时间和时间分析的参数估计相结合 到死亡时，我们将根据各种场景的认知功能来计算总生命年和无病生命年 这些分析的结果将提供患者的社会人口特征和癌症治疗。 关于人工智能暴露对认知的潜在不利影响的严格证据可以作为 他们还将生成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（超出正常认知衰老），这些治疗可用于 更好地告知患者不同乳腺癌治疗的“现实世界”权衡。 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都很重要 改善大量且不断增长的乳腺癌幸存者的功能和生活质量。