神经退行疾病由大脑和脊髓的细胞神经元逐渐退化死亡所致，按表现型分为两类：一类影响运动，例如帕金森病、多发性硬化、肌萎缩侧索硬化；一类影响记忆，例如阿尔茨海默病等痴呆症。
3月24日，《美国医学会杂志》网络开放版在线发表亚利桑那大学的研究报告，探讨了内分泌治疗与乳腺癌女性神经退行疾病风险的相关性。
该队列回顾研究于1月1～15日对1月1日～3月31日美国第三大医疗保险公司哈门那的索赔数据库进行回顾分析，该数据库包括美国各地以东南部居民为主的自付医疗保险和联邦医疗保险。其中，乳腺癌患者共计32万6485例，剔除年龄<45岁或男性患者2万1390例、有神经外科手术史或神经退行疾病史患者7478例、有其他癌症史患者109例、乳腺癌诊断之前6个月至之后至少3年内未连续参加医疗保险患者23万9665例，其余被诊断为乳腺癌1年后又被诊断为神经退行疾病且医疗保险索赔数据完整的年龄≥45岁女性患者共计5万7843例。内分泌治疗包括选择性雌激素受体调节剂或雌激素受体拮抗剂（他莫昔芬、雷洛昔芬）、芳香酶抑制剂（甾体类：依西美坦，非甾体类：阿那曲唑、来曲唑）。通过生存曲线法，分析内分泌治疗与神经退行疾病诊断的相关性。通过倾向评分匹配法，对乳腺癌诊断前的卒中和慢性阻塞性肺病史等其他影响因素进行校正，尽可能减少已知和未知的选择偏倚。
结果，其中曾接受内分泌治疗患者1万8126例（31.3%，平均年龄：76.2±7.0岁），未接受内分泌治疗患者3万9717例（68.7%，平均年龄：76.8±7.0岁）。平均随访5.5±1.8年。
经过倾向评分匹配，曾接受与未接受内分泌治疗的患者相比：
神经退行疾病发生比例低11%（12.5%比14.3%，相对风险：0.89，95%置信区间：0.84～0.93，P<0.001）
阿尔茨海默病发生比例低18%（4.9%比6.0%，相对风险：0.82，95%置信区间：0.75～0.90，P<0.001）
痴呆症发生比例低12%（10.4%比11.8%，相对风险：0.88，95%置信区间：0.83～0.93，P<0.001）
非阿尔茨海默病痴呆症发生比例相似
多发性硬化发生比例相似
帕金森病发生比例相似
肌萎缩侧索硬化发生比例相似
每减少1例疾病需要进行内分泌治疗的人数：
神经退行疾病：62.51
阿尔茨海默病：93.61
痴呆症：69.56
此外，进一步分析发现，曾接受与未接受他莫昔芬或甾体类芳香酶抑制剂（依西美坦）的患者相比，神经退行疾病、阿尔茨海默病、痴呆症、非阿尔茨海默病痴呆症发生比例较低；曾接受与未接受雷洛昔芬或非甾体类芳香酶抑制剂（阿那曲唑、来曲唑）的患者相比，神经退行疾病、阿尔茨海默病、痴呆症、非阿尔茨海默病痴呆症发生比例相似。
因此，该研究结果表明，对于中老年女性乳腺癌患者，接受与未接受内分泌治疗（尤其他莫昔芬或依西美坦）相比，神经退行疾病（尤其阿尔茨海默病和痴呆症）发生比例较低。由于近年来乳腺癌女性患者的寿命不断延长，故选择乳腺癌内分泌治疗方案时，应该考虑对减少神经退行疾病风险的可能性进行仔细讨论。
JAMA Netw Open. Mar 24;3(3):e41.
Association Between Hormone-Modulating Breast Cancer Therapies and Incidence of Neurodegenerative Outcomes for Women With Breast Cancer.
Gregory L. Branigan; Maira Soto; Leigh Neumayer,; Kathleen Rodgers; Roberta Diaz Brinton.
University of Arizona, Tucson; University of Arizona College of Medicine, Tucson.
This cohort study uses the Humana claims data set to examine whether exposure to hormone-modulating therapy is associated with the risk of neurodegenerative disease in women with breast cancer.
QUESTION: Is hormone-modulating therapy associated with neurodegenerative disease in women with breast cancer?
FINDINGS: In this cohort study of 57843 perimenopausal- to postmenopausal-aged women with breast cancer, exposure to hormone-modulating therapy (tamoxifen and aromatase inhibitors, especially exemestane) was associated with a significant decrease in the number of women who received a diagnosis of neurodegenerative disease, most specifically Alzheimer disease.
MEANING: With the increased life expectancy seen after treatment, therapy selection for breast cancer should include a careful discussion of the risks and benefits of each treatment option that may be associated with a reduced risk of neurodegenerative disease.
IMPORTANCE: The association between exposure to hormone-modulating therapy (HMT) as breast cancer treatment and neurodegenerative disease (NDD) is unclear.
OBJECTIVE: To determine whether HMT exposure is associated with the risk of NDD in women with breast cancer.
DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study used the Humana claims data set from January 1, , to March 31, . The Humana data set contains claims from private-payer and Medicare insurance data sets from across the United States with a population primarily residing in the Southeast. Patient claims records were surveyed for a diagnosis of NDD starting 1 year after breast cancer diagnosis for the duration of enrollment in the claims database. Participants were 57843 women aged 45 years or older with a diagnosis of breast cancer. Patients were required to be actively enrolled in Humana claims records for 6 months prior to and at least 3 years after the diagnosis of breast cancer. The analyses were conducted between January 1 and 15, .
EXPOSURE: Hormone-modulating therapy (selective estrogen receptor modulators, estrogen receptor antagonists, and aromatase inhibitors).
MAIN OUTCOMES AND MEASURES: Patients receiving HMT for breast cancer treatment were identified. Survival analysis was used to determine the association between HMT exposure and diagnosis of NDD. A propensity score approach was used to minimize measured and unmeasured selection bias.
RESULTS: Of the 326485 women with breast cancer in the Humana data set between and , 57843 met the study criteria. Of these, 18126 (31.3%; mean [SD] age, 76.2 [7.0] years) received HMT, whereas 39717 (68.7%; mean [SD] age, 76.8 [7.0] years) did not receive HMT. Mean (SD) follow-up was 5.5 (1.8) years. In the propensity score-matched population, exposure to HMT was associated with a decrease in the number of women who received a diagnosis of NDD (2229 of 17 878 [12.5%] vs 2559 of 17 878 [14.3%]; relative risk, 0.89; 95% CI, 0.84-0.93; P<0.001), Alzheimer disease (877 of 17 878 [4.9%] vs 1068 of 17 878 [6.0%]; relative risk, 0.82; 95% CI, 0.75-0.90; P<0.001), and dementia (1862 of 17 878 [10.4%] vs 2116 of 17 878 [11.8%]; relative risk, 0.88; 95% CI, 0.83-0.93; P<0.001). The number needed to treat was 62.51 for all NDDs, 93.61 for Alzheimer disease, and 69.56 for dementia.
CONCLUSIONS AND RELEVANCE: Among patients with breast cancer, tamoxifen and steroidal aromatase inhibitors were associated with a decrease in the number who received a diagnosis of NDD, specifically Alzheimer disease and dementia.
DOI: 10.1001/jamanetworkopen..1541
