The addition of chemotherapy to endocrine therapy in the treatment of early-stage hormone receptor-positive, HER2-negative breast cancer was associated with a significant increase in the level of perceived cognitive impairment, according to results of the TAILORx trial published in the Journal of Clinical Oncology.
Cancer-related cognitive impairment (CRCI), sometimes referred to as “chemobrain,” is a common and highly feared adverse effect associated with cancer diagnosis and treatment that can occur prior to the administration of chemotherapy. Current evidence suggests that multiple factors contribute to CRCI, including tumor burden, as well as cancer treatments, such as surgery, radiation therapy, chemotherapy, and endocrine therapy.
The design of the phase III TAILORx trial (ClinicalTrials.gov Identifier: NCT00310180), which was conducted in women with early-stage hormone receptor-positive, HER2-negative early-stage, node-negative breast cancer, provided the opportunity to separately evaluate the contribution of adjuvant chemotherapy to perceived cognitive impairment in the setting of a randomized study.
Specifically, a substudy of TAILORx involved a comparison of patient-reported outcomes regarding cognitive function in 2 balanced study arms in which patients classified as being at intermediate risk of disease recurrence were randomly assigned to receive adjuvant endocrine therapy with or without adjuvant chemotherapy. The focus of the primary endpoint of the substudy was on changes in patient-reported cognitive function as assessed using the validated Functional Assessment of Cancer Therapy-Cognitive Function (FACT-Cog) version 3 tool which was administered at baseline, and at 3, 6, 12, 24, and 36 months following initiation of treatment.
Of the 579 patients with baseline FACT-Cog assessments, corresponding data at 3, 6, 12, 24, and 36 months were available for 454, 469, 458, 476, 384, and 383 patients, respectively. In the chemotherapy-based study arm, 70% and 20% of patients were treated with docetaxel plus cyclophosphamide and anthracyline-based regimens, respectively. Regarding endocrine therapy, approximately 63% of patients received an aromatase inhibitor while the remaining patients were treated with tamoxifen.
At the 3-month assessment, 36.7% and 26.3% of patients treated with and without chemotherapy vs not reported cognitive impairment (P <.001). While a significant difference in patient-reported cognitive impairment was also observed when these respective groups were compared at 6 months (35.5% vs 30.7%; P =.02), it was no longer seen at 12 months (37.7% vs 35.3%) and beyond.
Regarding this finding, the study authors noted that “the trajectories of longitudinal FACT-Cog [perceived cognitive impairment] change scores by treatment arm converged over time largely because the [endocrine] arm reported a gradual increase in cognitive impairment at 12 months that persisted at 24 and 36 months.”
Notably, neither patient age nor menopausal status was associated with changes in perceived cognitive impairment.
“Our findings suggest an acute effect of chemotherapy on [perceived cognitive impairment], greater than observed with [endocrine therapy alone], which persists over time and is comparable to [endocrine therapy] at long-term follow-up,” the study authors commented in their concluding remarks.
They further noted that “increased impairment from pre- to posttreatment initiation observed in both groups underscores the need for clinical management of CRCI well beyond initiation of therapy, as well as the need for additional research to elucidate mechanisms and identify effective interventions.”
Wagner LI, Gray RJ, Sparano JA, et al. Patient-reported cognitive impairment among women with early breast cancer randomly assigned to endocrine therapy alone versus chemoendocrine therapy: results from TAILORx [published April 9, 2020]. J Clin Oncol. doi: 10.1200/JCO.19.01866