Abstract P1-11-21: Analysis of cognitive function in elderly HER2-positive breast cancer patients receiving either trastuzumab monotherapy or trastuzumab plus chemotherapy as a postoperative adjuvant treatment: A cognitive function sub-study of a randomized, open-label, phase 3 clinical trial (RESPECT trial)
Authors: Takahashi M , Sawaki M , Hagiwara Y , Uemura Y , Kawahara T , Shimozuma K , Ohashi Y , Saito T , Baba S , Kobayashi K , Mukai H , Taira N 
Published: May 2019

Abstract
OBJECTIVE: The effect of trastuzumab(Tmab) or chemotherapy on cognitive function has not been fully understood, especially in elderly breast cancer patients. The RESPECT trial compared 1-year(yr) Tmab monotherapy with Tmab plus standard chemotherapy as adjuvant therapy in elderly patients with HER2-positive breast cancer. The primary objective was to verify the noninferiority of 1-yr Tmab monotherapy compared to Tmab plus chemotherapy in terms of disease-free survival, and the planned analysis showed that the difference of restricted mean survival time between two groups at 3 yrs was 0.45 months (Sawaki at ASCO2018). The goal of this report was to assess the impact of the treatment groups on longitudinal cognitive function.
PATIENTS AND METHODS: The study was performed with patients from 99 hospitals in Japan. Elderly women with HER2-positive, stage I-IIIA invasive breast cancer surgery treated with clear resection margins were randomly assigned to either receive 1-yr Tmab or 1-yr Tmab plus standard chemotherapy. 15 institutions participated in the cognitive sub-study. Cognitive function was assessed using the Mini-Mental State Examination (MMSE) at baseline and at 1 and 3 yrs after treatment. The primary outcome was the amount of change in the MMSE score from the baseline. A linear mixed-effects model was used for comparisons of change in the MMSE score between groups, controlling for time and baseline score. Secondary outcomes were the proportion of both suspected mild dementia (MMSE≤27) and dementia (MMSE≤23) at each time point.
RESULTS: Between October 2009 and October 2014, 275 patients were enrolled in the RESPECT trial, and 57 patients were enrolled in the cognitive function sub-study with 2 patients subsequently excluded. The 55-patient sub-study comprised 29 patients assigned to the Tmab monotherapy group and 26 patients assigned to the Tmab plus chemotherapy group. Primary analysis revealed that change in the MMSE score was not significantly different between the two groups (difference −0.6 at 1 yr and −0.9 at 3 yrs; p=0.136), whereas the baseline score was the only significant factor that had an effect on the amount of change in the MMSE score (p&lt;0.001). The proportions of suspected mild dementia at baseline, and at 1 yr and 3 yrs were 15.4, 32.0, and 41.7% in the Tmab monotherapy group, and 45.8, 17.6, and 28.6% in the Tmab plus chemotherapy group. The proportions of suspected mild dementia at baseline were significantly higher in the Tmab plus chemotherapy group (p=0.04). The proportions of suspected dementia at baseline, and at 1 yr and 3 yrs were 0%, 0%, and 4.2% in the Tmab monotherapy group, and 4.2%, 0%, and 4.8% in the Tmab plus chemotherapy group. There were no significant differences in the proportions of suspected dementia between the treatment groups at each time point.
CONCLUSION: Postoperative chemotherapy for elderly breast cancer patients was considered to have little effect on the onset of dementia during the follow-up period of 3 yrs. Further long-term observation is necessary to obtain a significant conclusion.
Citation Format: Takahashi M, Sawaki M, Hagiwara Y, Uemura Y, Kawahara T, Shimozuma K, Ohashi Y, Saito T, Baba S, Kobayashi K, Mukai H, Taira N. Analysis of cognitive function in elderly HER2-positive breast cancer patients receiving either trastuzumab monotherapy or trastuzumab plus chemotherapy as a postoperative adjuvant treatment: A cognitive function sub-study of a randomized, open-label, phase 3 clinical trial (RESPECT trial) [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-11-21.