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 用抗雌激素剂（例如芳香酶抑制剂（AI））多于乳腺癌患者，而不是 除手术外的任何治疗方法。由于其有效性，最新的绝经后妇女指南 建议将AI疗法扩展到10年的持续时间。因此，超过350万 乳腺癌的存活很快就会增加。乳腺癌存活的主要关注点是治疗引起的 认知功能障碍。化疗期间约有75％的女性患有癌症相关的认知障碍 治疗，持续数月至数年。有理论和经验的理由相信 雌激素剥夺也可能发生认知障碍。令人惊讶的是，很少有经验人类 对AI对认知影响的研究；没有经过认知测量的前癌。利用18年的数据 健康和退休研究 - 医疗保险增强了全国代表性的纵向调查 医疗和药物主张，我们提出了一项纵向研究，旨在：（1）乳房的特征 癌症幸存者在60个月内调整AI疗法的定位后的认知功能 经过验证的神经心理学测量，并将其表现与（i）发生事件的妇女的表现进行比较 未接受AI疗法和（ii）非癌症控制的乳腺癌。横截面分析 对应于AI治疗后大约一年，三年和五年的倡议，将提供早期的估计 和AI的后期影响； （2）对比前后认知功能的纵向轨迹 接受AI治疗的女性的癌症诊断和治疗 在18年的时间内接受AI疗法和（ii）无癌症的对照。我们预计等级会下降 在研究期间，无癌女性的认知功能。但是，AI组有望 AI计划后展示钢筋向下向下斜坡，表明AI对上述认知的影响不利， 超出正常认知衰老； （3）量化整体和无疾病生活之间的权衡以及 患有不同可调疗法的乳腺癌妇女的认知功能。使用 AIM 2的发现以及从时间分析到疾病复发和时间的参数估计值 致死，我们将通过认知功能来计算整体和无疾病的生活年份 患者的社会人口统计学特征和癌症治疗。这些分析的结果将提供 关于AI暴露对认知的潜在不利影响的严格证据可能是 临床干预的基础。他们还将产生人口水平的生存和认知估计值 归因于AI和其他癌症治疗（超出正常认知衰老）的衰落，可用于 更好地将不同乳腺癌治疗的“现实世界”折衷告知患者。最后，我们的结果将 对于所有对更好地理解与癌症相关的认知障碍的挑战感兴趣的人都很重要 并改善大量乳腺癌生存的大量和越来越多的生活质量。