Abstract P6-05-06: Patient-reported anxiety and fatigue in women enrolled in the RxPONDER trial (SWOG S1007) by menopausal status
Authors: Loch Michelle M. , Forschmiedt Jamie K. , Kang Irene M. , Gralow Julie R. , Meric-Bernstam Funda , Albain Kathy S. , Hayes Daniel F. , Lin Nancy U. , Perez Edith A. , Goldstein Lori J. , Rastogi Priya , Schott Anne F. , Shak Steven , Sharma Priyanka , Lew Danika L. , Miao Jieling , Barlow William E. , Tripathy Debu , Pusztai Lajos , Hortobagyi Gabriel N. , Kalinsky Kevin , Henry N. Lynn 
Published: March 2023

Abstract
Introduction: Anxiety and fatigue have been reported by women undergoing cytotoxic and endocrine treatment (tx) for breast cancer and can have lasting effects on quality of life (QoL). The differential effects of menopausal (meno) status, tx allocation and duration of symptoms are not well established.
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 endocrine therapy (ET) alone vs chemotherapy followed by ET (CET). A subset of English speaking pts in the US at the start of the trial were invited to complete health-related QoL (HRQoL) questionnaires shortly after randomization (baseline; BL) and 6, 12, and 36 months after BL until accrual goal reached. BL surveys were completed in clinic; cognitive function results presented separately. Standardized T scores (mean 50; SD 10) were computed for anxiety (PROMIS Emotional Distress – Anxiety Short Form 7a) and fatigue (PROMIS Fatigue Short Form 7a). Higher T scores indicate more anxiety or fatigue. The primary endpoint of this exploratory analysis was to compare mean anxiety and fatigue T score by tx arm by meno status. Separately by meno status, a GEE model was fit to the three follow-up timepoints adjusting for BL to estimate the difference between tx arms and whether there was a time trend over the three follow-up measures.
Results: The accrual exceeded the goal of 500 pts with 74% of pts participating voluntarily until the QOL invitation was removed from the protocol (12/1/12). A total of 139 pre and 432 postmenopausal pts completed the anxiety questionnaire at BL. There was no difference in anxiety between tx arms [Table 1]. Mean anxiety score difference between CET and ET over time in the premenopausal cohort was -0.63 (p=0.63) and in the postmenopausal cohort was 0.59 (p=0.45). Although anxiety scores decreased over the three follow-up times, the change was not statistically significant.
A total of 139 pre and 429 postmenopausal pts completed the fatigue questionnaire at BL. Fatigue mean T scores in both the pre and postmenopausal cohorts were higher over time in the CET vs ET arm [Table 2]. Fatigue scores were 2.85 points higher for CET vs. ET over time in the premenopausal cohort (p=0.02) and 1.82 points higher in the postmenopausal cohort (p=0.007). Fatigue scores decreased over time for premenopausal (p=0.01), but not for postmenopausal (p=0.62) pts.
Dropoff occurred over time with 79%, 76%, 60% of pts at BL participating at 6, 12, and 36 months. Endocrine treatment adherence data are not yet available at each timepoint.
Conclusions: CET had a clinically significant negative effect on mean fatigue scores compared to ET alone in both pre and postmenopausal pts over time. Scores improved over time but did not return to BL. Pts had lower mean anxiety scores during tx compared to BL, but differences in scores between CET and ET groups out to 3 years did not significantly differ. Future therapeutic studies must continue to include HRQoL assessments to broaden our understanding of the full impact of chemotherapy and for the development of preventative and therapeutic strategies to manage these toxicities.
Table 1. Comparisons of mean Anxiety score by treatment arm and menopausal status.
Table 2. Comparisons of mean Fatigue score by treatment arm and menopausal status.
Citation Format: Michelle M. Loch, Jamie K. Forschmiedt, Irene M. Kang, 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, Danika L. Lew, Jieling Miao, William E. Barlow, Debu Tripathy, Lajos Pusztai, Gabriel N. Hortobagyi, Kevin Kalinsky, N. Lynn Henry. Patient-reported anxiety and fatigue in women enrolled 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 P6-05-06.