In Silico Psycho-Oncology: Understanding Resilience Pathways in Breast Cancer—Determinants of Longitudinal Depression and Quality-of-Life Trajectories

Background/Objectives: Patients with breast cancer show substantial heterogeneity in terms of psychological adjustment following diagnosis. We aimed to characterize longitudinal trajectories of quality of life (QoL) and depressive symptoms during the first 18 months post-diagnosis and to identify robust clinical, psychosocial, and behavioral predictors associated with distinct adjustment pathways. Methods: Women (N = 538; mean age 55.4 years; range 40–70) with operable breast cancer (stages I–III) were drawn from the multicenter BOUNCE cohort. QoL (Global Health Status/QoL scale of the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30) and depressive symptoms (depression subscale of the Hospital Anxiety and Depression Scale) were assessed at baseline and months 3, 6, 9, 12, 15 and 18. Latent class growth analysis and growth mixture modeling identified distinct trajectory classes. Associations between early predictors and trajectory membership were examined using logistic regression combined with elastic net regularization. Results: Depression trajectories demonstrated heterogeneity, with groups characterized by persistent resilience (59.7%), stable moderate/high (25.3%), delayed onset (5.0%), and recovery (10.0%). QoL trajectories ranged from stable excellent (13.2%) and stable high (40.7%) to moderate (31.4%) and persistent low/deteriorating (6.9%), as well as a distinct recovering trajectory (7.8%). Trajectory differentiation was primarily driven by psychological resources, symptom burden, functional status, and coping processes, alongside specific contributions from clinical factors. Conclusions: Distinct subgroups of women with breast cancer follow divergent adjustment pathways. These findings highlight the multidimensional nature of resilience and support the need for tailored interventions that promote long-term well-being beyond simple risk reduction.