Background: Depressive symptoms are associated with impaired quality of life and increased mortality among survivors of BC. We aimed to identify long-term patterns of depressive symptoms and their determinants, including potential interventional targets. Methods: Patients with stage I-III BC were included from CANTO (NCT01993498). Depressive symptoms were assessed by HADS (range 0-21) at diagnosis (pre-treatment [tx]) and year (Y)1, 2, 4, and 6. Group-based trajectory modeling and multinomial logistic regression identified latent groups at similar patterns of depressive symptoms and group membership determinants, respectively. Cox regression evaluated associations with clinically suggestive post-tx symptoms (HADS ≥11). Results: Among 9087 patients, we identified five patterns of depressive symptoms. Two groups, either at very low (23%) or low burden (45%), had flat patterns that almost never met the threshold for clinically suggestive symptoms (highest mean score [95% CI]: 1.4 [1.2-1.6] and 3.9 [3.5-4.3] at Y6, respectively). A stable group (6%) reported high symptom burden at diagnosis with some further post-tx deterioration (11.1 [10.7-11.6] at Y6). Two groups had changing patterns with the sharpest slope during primary tx: a remission group (7%) reported overtime improvements (baseline to Y6: 9.8 [9.4-10.2] to 5.1 [4.4-5.7]), whereas a worsening group (20%) showed consistent deterioration (5.1 [4.8-5.5] to 8.0 [7.7-8.3]). Older patients (adjusted Odds Ratio [95%CI] per 10 years, 1.09 [1.01-1.18]), those with previous psychiatric morbidity (v no, 1.75 [1.34-2.27]), obesity (v normal, 2.58 [2.02-3.29]), and income <1500 Eur/month (v ≥3000, 1.49 [1.22-1.81]) were more likely to belong to the worsening group than to the very low burden group. The worsening group also reported larger post-tx life interference, worry, and negative impact on employment and relationships. Table reports rates of clinically suggestive symptoms over time. Weight gain >5% (adjusted Hazard Ratio v stable, 1.32 [1.08-1.61]), reduced physical activity (v maintained, 1.31 [1.04-1.65]), increased alcohol use (v decreased, 3.70 [1.91-7.20]), worsened fatigue (v stable, 2.01 [1.61-2.51]), cognitive dysfunction (v stable, 1.98 [1.57-2.48]) and body image dissatisfaction (v no, 1.69 [1.33-2.15]) during primary tx (between diagnosis and Y1) were associated with clinically suggestive post-tx symptoms. Conclusions: Early screening and proactive follow-up are crucial to intercept psychological vulnerability. Trials of risk reduction interventions targeting pattern determinants since diagnosis and mitigating the psychological impact of cancer and health risk behaviors during primary tx seem warranted.< Réduire