Accelerated biological aging in breast cancer and risk for cognitive and physical complaints

项目总结 乳腺癌是女性最常见的癌症，新增病例超过26万例 预计仅2018年在美国就会出现。估计有300多万人患有乳腺癌。 由于检测和治疗方面的实质性进步，美国的幸存者人数继续增加 成长。然而，治疗也增加了长期和晚期毒性的风险，包括对身体和 影响生活质量的认知功能。最近提出的一种可能的解释是， 癌症治疗的毒性可能会直接加速某些患者的衰老过程，导致发病更早。 与年龄相关的症状，如认知主诉、疲劳、身体功能下降和持续性疼痛。 然而，这一假设尚未在临床人群中得到严格检验。我们的研究将考察 常见乳腺癌治疗的效果，因为它们与生物衰老、炎症和 在一项对乳腺癌患者进行前瞻性研究之前评估的躯体和认知主诉报告 以及在暴露于化疗和/或放射治疗之后。拟议的研究将利用现有的NCI- 在辅助治疗开始前评估的早期乳腺癌妇女的资助队列 放疗(RT)、化疗(CT)或内分泌治疗，在RT和/或CT完成后和 在治疗后6个月、12个月和18个月进行随访，连续采集血样检测血浆、DNA 和核糖核酸分析。在这个特征良好的乳腺癌幸存者队列中，我们建议增加 利用现有收集的标本评估生物衰老的标记物并增加新的行为 在治疗后7年进行评估，以1)检查乳腺癌治疗对生物学的影响 衰老过程，2)检验加速生物衰老与认知和生理的关系 乳腺癌患者在随访期内的主诉情况，以及3)检测是否存在炎症因素 调解生物老化与认知和身体不适之间的关系。

Project summary Breast cancer is the most common cancer in women, with over two-hundred and sixty thousand new cases expected in the United States in 2018 alone. There are estimated to be more than 3 million breast cancer survivors in the US due to substantial advances in detection and treatment, with this number continuing to grow. However, treatments also increase risk for long-term and late toxicities, including effects on physical and cognitive function that interfere with quality of life. One possible explanation recently proposed is that the toxicity of cancer treatments may directly accelerate the aging process in some patients, leading to earlier onset of age-related symptoms such as cognitive complaints, fatigue, declines in physical function, and lasting pain. However, this hypothesis has not been rigorously tested in clinical populations. Our study will examine the effects of common breast cancer treatments as they relate to markers of biological aging, inflammation, and reports of physical and cognitive complaints in a prospective study of breast cancer patients assessed prior to and after exposure to chemotherapy and/or radiotherapy. The proposed study will leverage an existing NCI- funded cohort of women with early-stage breast cancer assessed before onset of adjuvant therapy with radiation (RT), chemotherapy (CT), or endocrine therapy and again after completion of RT and/or CT and at follow-up visits occurring 6-, 12-, and 18-month post-treatment, with serial blood specimens for plasma, DNA and RNA analyses. In this well characterized cohort of breast cancer survivors, we propose to add the assessment of markers of biological aging using existing collected specimens and add a new behavioral assessment at 7 years post treatment to 1) examine the effects of breast cancer treatments on the biological aging process, 2) test the relationship between accelerated biological aging and cognitive and physical complaints in breast cancer patients over the follow-up period, and 3) test whether inflammatory factors mediate the relationship between biological aging and cognitive and physical complaints.