内分泌治疗对大脑功能的长期影响

　　2018年11月28日，美国癌症学会《癌症》在线发表洛杉矶加利福尼亚大学、大洛杉矶地区退伍军人医院的前瞻纵向研究报告，分析了乳腺癌患者接受内分泌治疗开始后长达6年期间对神经精神的影响。

　　该研究于2007～2011年入组早期乳腺癌患者189例，内分泌治疗开始后6个月（175例患者）、12个月（173例患者）、3～6年（102例患者）进行自我报告和神经精神评定，对学习能力、记忆力、注意力、视觉空间辨别能力、执行能力、执行速度进行定量比较。通过线性混合模型，根据接受内分泌治疗与否，分析神经精神表现或障碍发生率随着时间的变化。

　　结果，接受与未接受内分泌治疗的患者相比，任何时间点的神经精神表现或障碍未见显著不同。不过，入组该研究的大部分为白人和高学历患者，而且完成3～6年随访的102例患者入组时执行能力表现较好，也就是说未能完成3～6年随访的71例患者入组时执行能力表现较差，可能对结果带来影响。

　　因此，该组人群长期观察研究结果表明，接受与未接受内分泌治疗的早期乳腺癌存活者相比，未见内分泌治疗对大脑认知功能的不利影响。考虑到方法学复杂性，有必要开展进一步研究证实这些药物对大脑和认知功能的安全性。

Cancer. 2018 Nov 28. [Epub ahead of print]

The cognitive effects of endocrine therapy in survivors of breast cancer: A prospective longitudinal study up to 6 years after treatment.

Kathleen Van Dyk, Catherine M. Crespi, Julienne E. Bower, Steven A. Castellon, Laura Petersen, Patricia A. Ganz.

University of California at Los Angeles, Los Angeles, California; VA Greater Los Angeles Healthcare System, Los Angeles, California.

In the current study, the authors report no cognitive differences over time between survivors of breast cancer receiving endocrine therapy and those who are not. Further studies accounting for methodological complexities are needed to corroborate the safety of these medications on the brain and cognitive health.

BACKGROUND: After treatment of primary breast cancer, endocrine therapy (ET) is prescribed for patients with hormone receptor-positive cancers. Despite ET recommendations of 5 to 10 years of treatment, to the authors' knowledge there is little prospective study of its impact on cognitive function over an extended period of time. ET has known pharmacologic effects on the brain. Cognitive side effects are a concern for many women, with mixed findings reported in various studies. The current prospective longitudinal study examined the neuropsychological effects of ET over time, up to 6 years after treatment.

METHODS: A total of 189 survivors of early-stage breast cancer enrolled in the study prior to initiating ET if prescribed, and were followed at 6 months (175 patients), 12 months (173 patients), and for 3 to 6 years (102 patients) with self-report and neuropsychological assessments. Using linear mixed models, the authors examined whether neuropsychological performance or impairment rates differed over time based on whether or not ET was received.

RESULTS: The authors did not find any effect of ET on neuropsychological performance or impairment at any time point among survivors who received it compared with women who did not. However, those who participated in the 3-year to 6-year year visit demonstrated better executive function at baseline.

CONCLUSIONS: In the current observational cohort study, no detrimental effect of ET on cognitive function was identified in survivors of early-stage breast cancer receiving treatment with ET compared with those who were not.

DOI: 10.1002/cncr.31858