Stressful Life Events, Social Support, and Incident Breast Cancer by Estrogen Receptor Status.
Stressful Life Events, Social Support, and Incident Breast Cancer by Estrogen Receptor Status.
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DOI：
10.1158/1940-6207.capr-22-0472
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发表时间：
2023-05-01
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慢性压力会影响免疫功能和激素信号传导，并被假设与乳腺癌有关，尽管之前的少数研究结果参差不齐，并且没有检查雌激素受体 (ER) 状态的潜在差异。利用女性健康倡议研究，我们纳入了 76,951 名绝经后女性，对事件进行了平均 16.7 年的跟踪，以调查基线自我报告的压力生活事件与 ER 状态的乳腺癌事件之间的关联，以及该关联是否会通过社会支持而改变。我们生成了针对人口、临床、生活方式/行为和社会因素进行调整的 Cox 比例风险模型，以估计风险比 (HR) 和 95% 置信区间 (95%CI)。平均年龄为 63 岁 (SD 7.3)，大多数参与者是白人 (83.5%)，并已婚或处于类似婚姻关系 (63.0%)。在按 ER 状态分层的分析中，压力生活事件与 ER 阳性乳腺癌之间没有关系。相反，与最低四分位数的女性相比，较高四分位数的女性患 ER 阴性乳腺癌的风险增加，其中第四四分位数的女性风险最高（第四四分位数 vs 四分位数 1；HR=1.30；95%CI 1.01–1.68；Ptrend=0.050）。此外，丧偶妇女中压力生活事件的最高四分位数与最低四分位数的关联性更强（HR=2.39；95%CI 1.29–4.44；Pinteraction<0.001）。社会支持并未改变压力生活事件与 ER 阴性乳腺癌之间的关联。在这组绝经后女性中，诊断前经历过更多的压力生活事件与 ER 阴性乳腺癌的风险增加相关。
Chronic stress affects immune function and hormonal signaling and has been hypothesized to be associated with breast cancer, although results from the few prior studies are mixed and have not examined potential differences by estrogen receptor (ER) status. Using the Women’s Health Initiative Study, we included 76,951 postmenopausal women followed for events for a median of 16.7 years to investigate the association between baseline self-reported stressful life events and incident breast cancer by ER status and whether the association was modified by social support. We generated Cox proportional hazards models adjusting for demographic, clinical, lifestyle/behavioral, and social factors to estimate hazard ratios (HR) and 95% confidence intervals (95%CI). The mean age was 63 (SD 7.3), and majority of participants were White race (83.5%) and married or in a marriage-like relationship (63.0%). In analyses stratified by ER status, there was no relationship between stressful life events and ER-positive breast cancer. In contrast, compared to women in the lowest quartile, those in higher quartiles had an increased risk of ER-negative breast cancer, where those in quartile 4 had the highest risk (Quartile 4 vs Quartile 1; HR=1.30; 95%CI 1.01–1.68; Ptrend=0.050). Moreover, associations were stronger for the highest versus lowest quartile of stressful life events among widowed women (HR=2.39; 95%CI 1.29–4.44; Pinteraction<0.001). Association between stressful life events and ER-negative breast cancer was not modified by social support. In this cohort of postmenopausal women, higher experiences of pre-diagnostic stressful life events were associated with increased risk of ER-negative breast cancer.