Chemo-endocrine therapy has a greater negative effect on cancer-related cognitive impairment compared with endocrine therapy alone in both pre- and postmenopausal women, results from the RxRESPONDER PRO Substudy showed.


 

Breast cancer treatment is associated with cancer-related cognitive impairment. However, the effect of endocrine therapy versus chemotherapy followed by endocrine therapy (chemo-endocrine therapy) is not well understood, nor is the impact of menopausal status.1,2 Therefore, the impact of breast cancer treatment on cognition was explored in the RxRESPONDER PRO Substudy.

In this sub-study, the 8-item PROMIS Perceived Cognitive Function Concerns (PCF) questionnaire was completed at baseline and after 6, 12, and 36 months after randomization of 568 participants (N=274 treated with chemo-endocrine therapy, N=294 treated with endocrine therapy alone; N=139 premenopausal, N=429 postmenopausal). The primary endpoint of the sub-study was the mean cognitive function score by treatment arm and menopausal status. Dr. Irene Kang (City of Hope Orange County) presented the results at the 2022 San Antonio Breast Cancer Symposium.

In premenopausal participants treated with endocrine therapy alone, mean cognitive function score temporarily decreased after randomization and returned to baseline value by 36 months. In contrast, in premenopausal patients treated with chemo-endocrine therapy the score decreased after randomization and did not return to baseline value. The difference in longitudinal mean score between treatment arms (-3.02) was both statistically significant and clinically meaningful.

In postmenopausal participants treated with endocrine therapy alone, mean cognitive function score stayed stable during follow-up, while in postmenopausal participants treated with chemo-endocrine therapy, the score decreased after randomization and did not return to baseline value. The difference in longitudinal mean score between treatment arms (-2.36) was statistically significant but not clinically meaningful.

The change in cognitive function was, however, heterogeneous. In both treatment groups and in both pre- and postmenopausal participants, most did not show a clinically meaningful worsening of cognitive function score during follow-up. Their score kept stable or was (clinically meaningful) better during follow-up. The odds of having worse cognitive function were highest in postmenopausal participants treated with chemo-endocrine therapy at 12 months after randomization (OR, 2.24; 95% CI, 1.40-3.59).

“Chemo-endocrine therapy has a greater negative effect on cancer-related cognitive impairment compared with endocrine therapy alone both in pre- and postmenopausal women,” concluded Dr. Kang. “In addition, the effect of chemo-endocrine therapy seems to persist over time in a significant portion of patients.”

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