University of South Carolina, College of Pharmacy, Columbia.
South Carolina Revenue and Fiscal Affairs Office, Columbia, South Carolina.
JAMA Netw Open. 2024 Jul 1;7(7):e2422493. doi: 10.1001/jamanetworkopen.2024.22493.
Hormone-modulating therapy (HMT) is a widely accepted treatment for hormone receptor-positive breast cancer, although its cognitive effects, including a potential link to Alzheimer disease and related dementias (ADRD), remain understudied.
To investigate the association between HMT for breast cancer treatment and risk of developing ADRD in women aged 65 years or older.
DESIGN, SETTING, AND PARTICIPANTS: This cohort study used a comprehensive dataset from the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database to identify patients who did and did not receive HMT treatment within 3 years after the initial diagnosis of breast cancer and assessed their risk of developing ADRD in later life. Individuals with a preexisting diagnosis of ADRD or receiving HMT before the diagnosis of breast cancer were excluded. This study was performed from June 2022 through January 2024.
Receipt of HMT.
Risk of ADRD associated with HMT; associations of risk with age, self-identified race, and HMT type. Risk was measured using hazard ratios (HRs) with 95% CIs and adjusted for potential confounders such as demographic, sociocultural, and clinical variables.
Among 18 808 women aged 65 years and older diagnosed with breast cancer between 2007 and 2009 (1266 Black [6.7%], 16 526 White [87.9%], 1016 other [5.4%]), 12 356 (65.7%) received HMT within 3 years after diagnosis, while 6452 (34.3%) did not. The most common age group in both samples was the 75 to 79 years age group (HMT, 2721 women [22.0%]; no HMT, 1469 women [22.8%]), and the majority of women in both groups self-identified as White (HMT, 10 904 women [88.3%]; no HMT, 5622 women [87.1%]). During an average of 12 years of follow-up, 2926 (23.7%) of HMT users and 1802 (27.9%) of non-HMT users developed ADRD. HMT was associated with a 7% lower relative risk of ADRD overall (HR, 0.93; 95% CI, 0.88-0.98; P = .005). The association decreased with age and varied by race. The reduction in ADRD risk associated with HMT was greatest for women aged 65 to 74 years who self-identified as Black (HR, 0.76; 95% CI, 0.62-0.92). This association decreased among women aged 75 years or older (HR, 0.81; 95% CI, 0.67-0.98). Women aged 65 to 74 years who self-identified as White had an 11% relative risk reduction (HR, 0.89; 95% CI, 0.81-0.97), but the association disappeared for women aged 75 years or older (HR, 0.96; 95% CI, 0.90-1.02). Other races showed no significant association between HMT and ADRD. Age- and race-based associations also varied by HMT type.
In this retrospective cohort study, hormone therapy was associated with protection against ADRD in women aged 65 years or older with newly diagnosed breast cancer; the decrease in risk was relatively greater for Black women and women under age 75 years, while the protective effect of HMT diminished with age and varied by race in women. When deciding to use HMT for breast cancer in women aged 65 years or more, clinicians should consider age, self-identified race, and HMT type in treatment decisions.
激素调节疗法（HMT）是一种广泛接受的激素受体阳性乳腺癌治疗方法，尽管其认知影响，包括与阿尔茨海默病和相关痴呆症（ADRD）的潜在联系，仍在研究中。
研究乳腺癌治疗中 HMT 与 65 岁及以上女性发生 ADRD 的风险之间的关系。
设计、地点和参与者：这项队列研究使用了来自监测、流行病学和最终结果（SEER）-医疗保险数据库的综合数据集，以确定在乳腺癌初始诊断后 3 年内是否接受 HMT 治疗的患者，并评估他们在以后的生活中发生 ADRD 的风险。有 ADRD 既往诊断或在诊断乳腺癌前接受 HMT 的患者被排除在外。这项研究于 2022 年 6 月至 2024 年 1 月进行。
接受 HMT。
与 HMT 相关的 ADRD 风险；风险与年龄、自我认定的种族和 HMT 类型的关联。使用危险比（HR）和 95%置信区间（CI）来衡量风险，并对潜在的混杂因素进行了调整，如人口统计学、社会文化和临床变量。
在 2007 年至 2009 年间被诊断为乳腺癌且年龄在 65 岁及以上的 18808 名女性中（6.7%为黑人，16526 名为白人，1016 名为其他种族），12356 名（65.7%）在诊断后 3 年内接受了 HMT，而 6452 名（34.3%）未接受。在两个样本中，最常见的年龄组是 75 至 79 岁年龄组（HMT，2721 名女性[22.0%]；无 HMT，1469 名女性[22.8%]），大多数女性自我认定为白人（HMT，10904 名女性[88.3%]；无 HMT，5622 名女性[87.1%]）。在平均 12 年的随访中，2926 名（23.7%）HMT 使用者和 1802 名（27.9%）非 HMT 使用者发生了 ADRD。总体而言，HMT 与 ADRD 的相对风险降低了 7%（HR，0.93；95%CI，0.88-0.98；P=0.005）。这种关联随着年龄的增长而降低，并且因种族而异。HMT 与 ADRD 风险降低的关联在自我认定为黑人的 65 至 74 岁女性中最大（HR，0.76；95%CI，0.62-0.92）。这种关联在 75 岁及以上的女性中降低（HR，0.81；95%CI，0.67-0.98）。自我认定为白人的 65 至 74 岁女性的相对风险降低了 11%（HR，0.89；95%CI，0.81-0.97），但 75 岁及以上女性的关联消失（HR，0.96；95%CI，0.90-1.02）。其他种族的 HMT 与 ADRD 之间没有显著关联。基于年龄和种族的关联也因 HMT 类型而异。
在这项回顾性队列研究中，激素治疗与新诊断为乳腺癌的 65 岁及以上女性的 ADRD 保护作用相关；黑人女性和年龄在 75 岁以下的女性的风险降低幅度相对较大，而 HMT 的保护作用随着年龄的增长而降低，并且在女性中因种族而异。当决定为 65 岁及以上的女性使用 HMT 治疗乳腺癌时，临床医生应在治疗决策中考虑年龄、自我认定的种族和 HMT 类型。
