Cognitive Impairment and Chemoendocrine vs Endocrine Therapy in Pre- and Postmenopausal Women: A Secondary Analysis of the RxPONDER Randomized Clinical Trial.

However, the association of endocrine therapy (ET) vs chemotherapy plus endocrine therapy (CET) with CRCI is poorly understood.

然而，内分泌治疗（ET）与化疗加内分泌治疗（CET）与CRCI的关联尚不明确。

Background

To compare patient-reported CRCI between women with breast cancer treated with ET vs CET and to consider whether menopausal status may be associated.

比较接受内分泌治疗（ET）与化疗联合内分泌治疗（CET）的乳腺癌女性患者报告的认知障碍（CRCI），并考虑绝经状态是否可能与之相关。

DESIGN, SETTINGS, AND PARTICIPANTS: This was a prespecified secondary analysis of RxPONDER (SWOG S1007), a multinational phase 3 randomized clinical trial of more than 5000 women with hormone receptor-positive ERBB2-negative (formerly HER2-negative) breast cancer with 1 to 3 involved lymph nodes and Oncotype DX (21-gene recurrence score) of 25 or less.

设计、设置和参与者：这是RxPONDER（SWOG S1007）的预定次要分析，这是一个涉及超过5000名激素受体阳性、ERBB2阴性（前称HER2阴性）乳腺癌患者的大规模III期随机临床试验，这些患者有1至3个受累淋巴结，且Oncotype DX（21基因复发评分）为25或以下。

Participants were enrolled from February 2011 to September 2017, with results first reported in December 2020.

研究对象从2011年2月起至2017年9月被纳入，首次报告结果于2020年12月。

Participants were randomly assigned to CET or ET, with ongoing follow-up.

参与者被随机分配至CET（综合治疗组）或ET（标准治疗组），目前随访仍在进行中。

This secondary analysis assessed cognitive function using the Patient-Reported Outcomes Measurement Information System Perceived Cognitive Function Concerns (PCF) questionnaire at baseline, 6, 12, and 36 months.

这项次要分析使用患者报告的结果测量信息系统感知认知功能关注（PCF）问卷，在基线、6个月、12个月和36个月时评估了认知功能。

Data were analyzed from July 2022 to August 2025.

数据分析的时间范围是从2022年7月到2025年8月。

intervention

Random assignment to CET or ET.

随机分配至CET或ET。

main_outcomes_and_measures

Mean PCF standardized (T) scores by menopausal status over time using generalized estimating equations analysis for continuous outcomes.

使用广义估计方程分析连续结果，按绝经状态随时间的平均PCF标准化（T）分数。

Results

Of the 568 patients who completed the baseline questionnaire and were included in the analysis, 139 (24%) were premenopausal (median [range] age, 47.8 [28.0-56.3] years) and 429 (76%) were postmenopausal (median [range] age, 62.3 [37.3-87.6] years).

在完成基线问卷并纳入分析的568名患者中，139名（24%）为绝经前女性（中位年龄[范围]，47.8 [28.0-56.3]岁），429名（76%）为绝经后女性（中位年龄[范围]，62.3 [37.3-87.6]岁）。

Among the 274 (48%) who received CET and the 294 (52%) who received ET alone, CET was determined to have a greater negative association with patient-reported CRCI in both the pre- and postmenopausal participants during the 36-month follow-up.

在274名（48%）接受CET治疗和294名（52%）仅接受ET治疗的患者中，CET在36个月的随访期间被确定为与绝经前和绝经后参与者的患者报告的CRCI有更大的负相关性。

In the ET alone group, PCF scores for premenopausal participants decreased from baseline to 6 and 12 months (53.53, 51.51, and 51.72, respectively) but recovered to baseline (54.36) at 36 months.

在单独接受ET治疗的组中，绝经前参与者的PCF评分从基线到6个月和12个月时有所下降（分别为53.53、51.51和51.72），但在36个月时恢复到基线水平（54.36）。

For postmenopausal participants, mean PCF scores were essentially stable (51.72, 51.13, 51.11, and 51.70, respectively); however, in the CET group, PCF scores for both pre- and postmenopausal participants decreased from baseline to 6 and 12 months (premenopausal, 52.84, 49.27, 48.04; postmenopausal, 50.65, 48.39, 47.13, respectively) and did not return to baseline at 36 months (premenopausal, 49.25; postmenopausal, 48.44).

对于绝经后参与者，平均PCF评分基本保持稳定（分别为51.72、51.13、51.11和51.70）；然而，在CET组中，无论是绝经前还是绝经后参与者的PCF评分从基线到6个月和12个月时都有所下降（绝经前分别为52.84、49.27、48.04；绝经后分别为50.65、48.39、47.13），并且在36个月时没有恢复到基线水平（绝经前为49.25；绝经后为48.44）。

The difference in longitudinal mean PCF scores over time between CET and ET groups was -3.02 (95% CI, -5.33 to -0.72; P = .01) for premenopausal and -2.37 (95% CI, -3.92 to -0.82; P = .003) for postmenopausal participants.

在CET和ET组之间，随时间变化的纵向平均PCF评分差异对于绝经前参与者为-3.02（95%置信区间，-5.33至-0.72；P = .01），对于绝经后参与者为-2.37（95%置信区间，-3.92至-0.82；P = .003）。

conclusions_and_relevance

This secondary analysis of the RxPONDER found that CET had a greater negative association with patient-reported CRCI compared to ET alone in both pre- and postmenopausal participants over a 36-month follow-up period.

这项对RxPONDER的次要分析发现，在36个月的随访期间，与单独使用ET相比，CET与绝经前和绝经后参与者的患者报告的CRCI有更大的负相关性。

Interventions to prevent or treat CRCI are needed to improve the long-term quality of life of these patients treated with chemotherapy.

需要采取干预措施来预防或治疗化疗相关认知障碍（CRCI），以改善这些接受化疗治疗患者的长期生活质量。

trial_registration

ClinicalTrials.gov Identifier: NCT01272037.

ClinicalTrials.gov 注册号：NCT01272037。