Sleep, Inflamation, and Depression Occurrence in Breast Cancer Survivors

描述(申请人提供)：2006年，美国有超过1140万癌症幸存者。然而，对于许多癌症患者来说，包括抑郁在内的长期行为影响使存活率的提高变得复杂。事实上，乳腺癌幸存者的抑郁症患病率几乎是普通人群的三到五倍。然而，导致乳腺癌存活者抑郁风险增加的独特临床、行为和生物因素尚不清楚。在老年人中，我们发现睡眠障碍独立地导致抑郁症的发生，并且这种预期风险特定于那些有抑郁症病史的人。乳腺癌的状况可能会增加这种风险，因为我们 研究发现，患有失眠的乳腺癌幸存者有抑郁症史的患病率几乎是患有失眠的老年女性的两倍；然而，先前风险模型中的其他因素并不适用于乳腺癌幸存者。目前还没有已发表的前瞻性数据来检验睡眠障碍对乳腺癌幸存者抑郁发生的独立贡献。越来越多的证据还表明，睡眠障碍与炎症信号的激活有关，炎症信号是导致抑郁症的一种生物学机制。因此，在这项基于SEER附属肿瘤登记的研究中，我们将评估300名早期、老年(55岁)乳腺癌幸存者和300名年龄匹配的对照女性，按严重抑郁症病史分层。所有参与者都将是南加州凯撒永久医疗计划(KPSC)的社区成员，这是一项大型非营利性医疗计划，服务于300多万成员。在一项前瞻性队列研究中，将在基线(即乳腺癌幸存者接受初级治疗后1年)以及6、12、18和24个月对老年乳腺癌幸存者与对照进行评估，目的如下：1)确定睡眠障碍和抑郁发生之间的预期联系；2)评估睡眠障碍与炎症细胞和基因组标志物之间的预期联系；以及3)检查睡眠障碍、炎症细胞和基因组标志物与抑郁发生之间的预期关系。了解癌症特定的临床、行为和生物因素对乳腺癌幸存者与老年女性相比可能导致抑郁风险的预期贡献，将极大地改变临床管理，从而导致专门针对乳腺癌幸存者的抑郁症预防的有针对性的干预措施的开发。

DESCRIPTION (provided by applicant): In 2006, there were over 11.4 million cancer survivors in the US. However for many individuals with cancer, improved survival is complicated by long-term behavioral effects including depression. Indeed, the prevalence of depression in breast cancer survivors is nearly three to five times greater than the general population. Yet, the unique clinical, behavioral, and biological factors that prospectively contribute to increased depression risk in breast cancer survivors is not known. In older adults, we have found that sleep disturbance independently contributes to depression occurrence, and this prospective risk is specific to those with a history of depression. Breast cancer status may add to that risk, as we have found that breast cancer survivors with insomnia have a prevalence of depression history that is nearly twice that in older women with insomnia; yet, other factors in the prior risk model do not generalize to breast cancer survivors. There are no published prospective data that have examined the independent contribution of sleep disturbance on depression occurrence in breast cancer survivors. Increasing evidence also implicates sleep disturbance in the activation of inflammatory signaling, which serves as a biological mechanism that contributes to depression. Hence, in this SEER-affiliated tumor registry-based study, we will evaluate 300 early stage-, older adult (>55 years) breast cancer survivors and 300 age-matched comparison women, stratified by a history of major depression. All participants will be community members of Kaiser Permanente Southern California (KPSC), a large nonprofit health plan that serves over 3 million members. In a prospective cohort study, older adult breast cancer survivors vs. comparisons, stratified by depression history will be evaluated at baseline (i.e., 1 year post- primary treatmen for breast cancer survivors) and at 6, 12, 18, and 24 months with the following aims: 1) to determine the prospective association between sleep disturbance and depression occurrence; 2) to evaluate the prospective association between sleep disturbance and cellular and genomic markers of inflammation; and 3) to examine the prospective relationships between sleep disturbance, cellular and genomic markers of inflammation, and depression occurrence. Understanding the cancer-specific clinical, behavioral, and biological factors that prospectively contribute to depression risk in breast cancer survivors vs. comparison older women will substantially alter clinical management by leading to the development of a targeted intervention for depression prevention, specific for breast cancer survivors.