Baseline telomere length and prediction of cognitive recovery after chemotherapy in patients with breast cancer: An NCORP prospective cohort study.

Abstract

12149 Background: Chemotherapy-related cognitive impairment (CRCI) affects up to 70% of breast cancer survivors, yet recovery varies. Telomere length (TL), a marker of biological aging, may reflect biological resilience to CRCI. We evaluated whether baseline TL predicts longitudinal cognitive recovery following chemotherapy. Methods: In a nationwide prospective cohort study across 19 NCORP-affiliated community oncology clinics (URCC 10055), 185 women with stage I–IIIC breast cancer were assessed before chemotherapy (T1), post-chemotherapy (T2), and 6 months post-chemotherapy (T3). Baseline TL was measured by qPCR, normalized, and categorized into three groups: Short (S, n = 63, 34.1%), Average (A, n = 75, 40.5%), and Long (L, n = 47, 25.4%). Perceived cognitive function was assessed using the Functional Assessment of Cancer Therapy–Cognitive Function (FACT-Cog; minimum clinically important difference for total ≈7 pts), including total score and subscales for perceived cognitive impairments (PCI), perceived cognitive abilities (PCA), comments from others (OTH), and impact on quality of life (QoL). Changes from T1→T2 and T2→T3 were evaluated using repeated-measures mixed-effects analysis of covariance models adjusted for baseline values. Results: Baseline FACT-Cog total scores were similar across TL groups. At T2, all groups experienced comparable acute PCI (FACT-Cog change: S = −13.2, A = −13.3, L = −18.7). By T3, recovery differed by TL. While all groups remained below baseline, patients with long TL demonstrated substantially greater recovery, with a smaller overall decline from T1 (L = −8.6) compared with persistent impairment in Short (S = −14.0) and Average (A = −11.4) groups. This reflected a clinically meaningful improvement in cognitive function from post-chemotherapy to 6-month of +10.0 pts in the Long group (p = .016), whereas changes in the other two groups was not clinically or statistically significant. This recovery pattern was supported by clinically significant improvement in PCI (+7.2) and statistically significant change in OTH (+1.0; p = .003) in the Long group from T2 to T3, while it was attenuated in the Average and Short groups. In contrast, PCA showed minimal change across groups. Impact on quality of life also improved significantly in the Long group over the same period (FACT-Cog QoL T3–T2 change = +2.0; p = .019), reinforcing a coherent cognitive recovery phenotype. Conclusions: Baseline TL does not determine susceptibility to acute chemotherapy-related toxicity but strongly predicts cognitive recovery over time. Patients with longer telomeres demonstrate clinically meaningful recovery of cognition, whereas those with shorter telomeres show more persistent perceived cognitive impairment. TL may identify patients at higher risk for long-term impairment who could benefit from early supportive and rehabilitative interventions.