Trajectories of cancer-related behavioral symptoms (CRBS) burden after breast cancer (BC).
Authors: Pagliuca Martina , Havas Julie , Lapidari Pietro , Menvielle Gwenn , Fasse Leonor , Boinon Diane , Martin Anne-Laure , Everhard Sibille , Jouannaud Christelle , Fournier Marion , Jacot William , Vanlemmens Laurence , Kaderbhai Coureche , Joly Florence , De Laurentiis Michelino , Scotte Florian , Michiels Stefan , Franzoi Maria Alice B , Luis Ines Maria Vaz Duarte , Di Meglio Antonio 
Published: June 2024

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Background: Fatigue, cognitive impairment, anxiety, depression, and insomnia are prevalent CRBS that share common risk factors and often aggregate in clusters. We aimed to characterize the evolution of CRBS burden after early-stage BC. Methods: Patients with stage I-III BC were included from the CANTO cohort (NCT01993498). Group-based trajectory modeled CRBS burden as assessed by Behavioral Symptoms Score (BSS) reported at diagnosis and at year (Y)1, Y2, Y4, and Y6 post-diagnosis (continuous, range 0-5; 1 point per clinically meaningful symptom reported among fatigue [EORTC QLQ-C30 ≥40/100], cognitive impairment [<75/100], insomnia [>50/100], anxiety or depression [HADS ≥11/21]). Trajectory membership factors were investigated using multinomial regression. Results: Among 10782 patients with BSS available at ≥1 time point, we identified 6 trajectories of CRBS: low-burden (21%), late-onset (5%), early-onset (11%), progressively improving (15%), high-burden (37%), and very high-burden (10%). The early-onset group did not report clinically meaningful symptoms at diagnosis but experienced early and persistent post-treatment (tx) worsening: at Y1, 50% had cognitive impairment, 48% fatigue, 45% insomnia, 13% anxiety, and 4% depression. 19% of patients in the early-onset group reported a cluster of ≥3 CRBS at Y1 (Table). Factors associated with membership to early-onset (v low-burden) group included age (adjusted Odds Ratio for 10-year decrement, 1.22 [95% CI 1.04 - 1.34]), monthly income <1500 euro (v ≥3000, 1.48 [1.08 - 2.04]), BMI ≥25 kg/m2 (v <25, 1.27 [1.07 - 1.52]), psychiatric comorbidity (v no, 1.44 [1.12 - 1.86]), chemotherapy (v no, 1.48 [1.19 - 1.84]) and endocrine tx (v no, 1.49 [1.19 - 1.86]). The early-onset group was also characterized by high and persistent rates of post-tx amenorrhea (77% at Y1 and 69% at Y6). In the early-onset group, overweight/obesity (49%) and inactivity (41%) were common at diagnosis. Over time, patterns of behavioral traits including increasing BMI were similar in the early-onset and the persistently high burden groups, whereas trends toward increased physical activity were observed in groups at low burden or progressively improving CRBS (both p for trend <.001). Conclusions: Longitudinal trajectories of CRBS were heterogeneous in this large prospective cohort. Clinicians should be aware that initially asymptomatic women may develop clinically meaningful post-tx CRBS, including several reporting clusters of ≥3 CRBS for years after diagnosis. This study highlights factors that can help screening patient at risk of deteriorated symptom burden and suggests potentially interventional targets, capitalizing on healthy lifestyle promotion. [Table: see text]