Abstract P4-11-09: Cancer-related cognitive impairment (CRCI) in early breast cancer (BC) survivors
Authors: Presti Daniele , Joly Florence , Soldato Davide , Christodoulidis Stergios , Noce Antonin Della , Havas Julie , Dubuisson Florine , Pistilli Barbara , Camara-Clayette Valerie , André Fabrice , Martin Anne-Laure , Jacquet Alexandra , Boyault Sandrine , Bièche Ivan , Coutant Charles , Cournede Paul-Henry , Michiels Stefan , Pradon Caroline , Vaz-Luis Ines , Meglio Antonio Di 
Published: March 2022

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 &lt; 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&lt;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.

Table 1.Models of severe CRCI in the overall cohort: clinical predictors.T1 (N=7724)T2 (N=6825)T3 (N=4706)OR* (95% CI)OR* (95% CI)OR* (95% CI)Severe Pain**, vs no1.50 (1.09-2.07)1.93 (1.39-2.69)1.55 (1.03-2.34)Severe pre-tx CRCI**, vs no3.69 (2.70-5.05)2.53 (1.85-3.46)2.21 (1.47-3.32)Severe Fatigue**, vs no1.50 (1.06-2.11)1.61 (1.13-2.28)1.08 (0.69-1.70)Age (continous)0.98 (0.97-0.99)NR0.98 (0.96-0.99)Menopause, post- vs pre-NR0.73 (0.54-0.98)NRAnxiety, case vs normalNRNR1.82 (1.13-2.92)Anxiety, borderline vs normalNRNR1.84 (1.17-2.91)Hot flashes, vs no1.25 (0.92-1.69)1.20 (0.87-1.65)1.64 (1.10-2.43)Corrected AUC0.73 (0.70-0.76)0.69 (0.65-0.72)0.68 (0.63-0.72)OR= Odds Ratio, CI= Confidence Interval, NR= Not Retained; *Adjusted by BMI, alcohol, smoke, socioeconomic, psychological, tumor and tx; **QLQ-C30

Table 2.Models of severe CRCI in the overall cohort**: biological biomarkers.T1 (N=1094)T2 (N=1091)T3 (N=870)OR* (95% CI)OR* (95% CI)OR* (95% CI)IL6NR0.80 (0.46-1.40)1.01 (0.64-1.60)IL1RA0.66 (0.37-1.17)0.88 (0.50-1.55)NRCRP0.94 (0.60-1.48)1.44 (0.92-2.27)NRIL20.93 (0.55-1.57)1.10 (0.61-1.97)NRIL1βNR1.55 (0.71-3.40)NRIFNγ1.86 (0.69-5.01)0.75 (0.25-2.22)NRIL101.05 (0.34-3.27)1.27 (0.58-2.78)NRIL1A0.71 (0.15-3.33)0.80 (0.17-3.66)NRIL80.96 (0.58-1.58)NRNRTNFαNR1.35 (0.67-2.73)NRMCP-11.07 (0.64-1.78)0.83 (0.51-1.35)0.80 (0.48-1.31)Corrected AUC0.72 (0.67-0.77)0.70 (0.65-0.75)0.67 (0.62-0.72)OR= Odds Ratio, CI= Confidence Interval, NR= Not Retained; *Adjusted by BMI, alcohol, smoke, socioeconomic, psychological, tumor and tx; ** Clinical predictors from previous models were forced in the models at each time-point

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.