Introduction: Breast cancer treatment is associated with cancer-related cognitive impairment (CRCI). However, the differential effect of endocrine therapy (ET) vs chemotherapy followed by endocrine therapy (CET), including the impact of menopausal status, on CRCI is not well understood.

Methods: Participants (pts) with hormone receptor positive, HER2 negative breast cancer with 1-3 positive lymph nodes and an Oncotype DX recurrence score of 0-25 enrolled in the RxPONDER trial were randomly assigned to ET alone versus CET. Until the health-related quality of life (HRQoL) accrual goal was reached, English speaking pts in the US were invited to complete HRQoL questionnaires including the 8-item PROMIS Perceived Cognitive Function Concerns (PCF) Short Form questionnaire shortly after randomization (baseline), as well as 6, 12, and 36 months after baseline. Analysis of measures of anxiety and fatigue is presented separately. Standardized T scores (mean 50; SD 10) for PCF were computed with higher scores indicating less cognitive impairment. The primary endpoint of this exploratory analysis was to compare mean PCF T scores by treatment arm and menopausal status. Separately by menopausal status, a generalized estimating equations (GEE) model was fit to the three timepoints adjusting for baseline to estimate the difference between treatment arms and whether there was a time trend over the three follow-up measures.

Results: The HRQoL accrual exceeded the goal of 500 patients, with 74% of pts participating voluntarily until the QOL invitation was removed from the protocol (Dec 1, 2012). A total of 139 pre and 429 postmenopausal pts completed the questionnaires at baseline. T scores were similar between ET and CET arms at baseline [Table 1]. In the ET arm, T scores decreased from baseline to 6 and 12 months but recovered to baseline at 36 months. In the CET arm, T scores decreased from baseline to 6 months and 12 months but did not return to baseline at 36 months. The mean score difference between CET and ET over time was -3.02 (p=0.01) and -2.36 (p=0.003) for pre and postmenopausal pts, respectively. Adjusting for baseline, there was no significant time trend over the three follow-up periods for either premenopausal (p=0.12) or postmenopausal (p=0.49) pts. Dropoff occurred over time with 79%, 76%, 60% of pts at baseline participating at 6, 12, and 36 months. Complete endocrine treatment adherence data are not yet available at each timepoint.

Conclusion: Chemoendocrine therapy has a greater negative effect on patient-reported CRCI compared to ET alone in both pre- and post-menopausal pts and it is sustained over 36 months. Interventions to prevent or treat CRCI are needed to improve the long-term quality of life of patients treated with CET.

Table 1.

Comparisons of mean Cognitive Function score by treatment arm and menopausal status.

Comparisons of mean Cognitive Function score by treatment arm and menopausal status.
Comparisons of mean Cognitive Function score by treatment arm and menopausal status.

Citation Format: Irene Kang, Jamie K. Forschmiedt, Michelle M. Loch, William E. Barlow, Danika L. Lew, Julie R. Gralow, Funda Meric-Bernstam, Kathy S. Albain, Daniel F. Hayes, Nancy U. Lin, Edith A. Perez, Lori J. Goldstein, Priya Rastogi, Anne F. Schott, Steven Shak, Priyanka Sharma, Jieling Miao, Debu Tripathy, Lajos Pusztai, Gabriel N. Hortobagyi, Kevin Kalinsky, N. Lynn Henry. Patient-reported cognitive impairment in women participating in the RxPONDER trial (SWOG S1007) by menopausal status [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr GS1-04.