Abstract P4-11-09: Cancer-related cognitive impairment (CRCI) in early breast cancer (BC) survivors

Background: Up to 35% BC survivors who receive adjuvant treatment (tx) experience severe CRCI, which has a significant impact on quality of life, disrupting daily functioning as well as self-esteem, self-confidence, and work ability. However, limited tools exist to predict the risk of CRCI. We aimed to develop a comprehensive model of severe CRCI, including clinical and serum inflammatory protein data. Methods: We included 8875 patients (pts) with stage I-III BC from the multicenter, prospective CANTO cohort (NCT01993498). Longitudinal data were collected at diagnosis (dx), 1 (T1), 2 (T2) and 4 (T3) years post-dx. Our outcome of interest was severe cognitive impairment at T1, T2, and T3 (score < 75/100, EORTC QLQ-C30, Giesinger JM 2020). Multivariable logistic regression models retained associations between baseline clinical variables (sociodemographic, psychological, tumor, and tx-related) with severe CRCI by bootstrapped Augmented Backwards Elimination (ABE). Among a subset of patients with HR+/HER2- BC (N= 1151), blood samples were profiled at dx using a multi-biomarker inflammatory panel assessing IL6, TNFα, IL1RA, CRP, IL2, IL1β, IFNγ, IL10, IL1A, IL4, IL8, and monocyte chemoattractant protein-1 (MCP-1). All biomarkers were incorporated simultaneously into a model of severe CRCI and retained only if significantly associated with CRCI by ABE (p<0.05). Previously retained clinical associations were forced into the model. Results: In the overall cohort, mean age at dx was 56.7 years (SD 11.3), and 52.7% and 81.3% of pts received chemotherapy and hormonal therapy, respectively. Prevalence rates of severe CRCI were 31.2% (dx), 31.4% (T1), 30.9% (T2), and 29.9% (T3). Severe post-tx CRCI was consistently associated with severe pre-tx pain and severe pre-tx CRCI. Severe pre-tx fatigue, younger age, anxiety symptoms and hot flashes at dx were also associated with increased odds of severe CRCI at some post-dx time-points (Table 1). Models Area Under the Curve (AUC) were 0.73 (95% confidence intervals [CI] 0.70-0.76) at T1, 0.69 (CI 0.65-0.72) at T2, and 0.68 (CI 0.63-0.72) at T3. Among pts with available serum biomarkers, no significant associations were observed between inflammatory proteins and CRCI at any time point. Performance of models incorporating inflammatory biomarkers was similar to clinical-only models (Table 2). Conclusions: Almost 1/3 of BC survivors in this cohort reported severe CRCI. This rate was stable throughout the survivorship period and did not seem to be affected by cancer-specific or tx-related factors, or inflammatory biomarkers. Pts age and concomitant symptom burden at dx emerged as consistent associations with severe CRCI. A description of the average population risk of CRCI using a self-reported, global evaluation scale may not fully describe the granularity of this phenomenon. Further studies building on dedicated, objective measurements, may help identify latent classes of pts experiencing a major decline in cognitive function following BC tx, and for whom a contribution of biology may help explain inter-individual variability and underlying biological processes.

Citation Format: Daniele Presti, Florence Joly, Davide Soldato, Stergios Christodoulidis, Antonin Della Noce, Julie Havas, Florine Dubuisson, Barbara Pistilli, Valerie Camara-Clayette, Fabrice André, Anne-Laure Martin, Alexandra Jacquet, Sandrine Boyault, Ivan Bièche, Charles Coutant, Paul-Henry Cournede, Stefan Michiels, Caroline Pradon, Ines Vaz-Luis, Antonio Di Meglio. Cancer-related cognitive impairment (CRCI) in early breast cancer (BC) survivors [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P4-11-09.