Background: Breast cancer (BC) treatments and their related-adverse effects may affect or delay the return to work (RTW) process. However, most of the studies lacked in considering the temporal and sequential aspects of care trajectories on RTW. Method: Our study population included working-age women diagnosed with a BC from 2012 to 2018 identified in the CONSTANCES French cohort. Patients’ BC treatments, antidepressants/anxiolytic and antalgic deliveries, used as proxy for depression and pain respectively, and daily sickness allowance, used to estimated RTW and time to RTW, were assessed monthly using the French national healthcare system database. BC care trajectories were identified using the sequence analysis method. Time-dependant Cox models were performed to investigate the effect of BC care trajectories and their related effects on both RTW and time to RTW, adjusting for age and socioeconomic characteristics. Results: 85.2% patients returned to work within two years after diagnosis with a median time to RTW of 297 days. Five patterns of BC care trajectories were identified: (i) BC surgery only, (ii) BC surgery & radiotherapy (iii) BC surgery & chemotherapy (iv) BC surgery & chemotherapy & radiotherapy (v) BC surgery & long-term alternative chemotherapy/radiotherapy. Hazards ratios of non-RTW were significantly increased among older (> 55 years-old) patients belonging to the most complex BC care trajectories (pattern v). Time to RTW was significantly increased in patients that underwent chemotherapy in their BC care trajectory (from iii to v) and in patients with antidepressant/anxiolytic and antalgic deliveries. Conversely, time to RTW decreased for BC patients benefiting from high household income or single-parent family. Conclusion: This study highlights the necessity to consider the dynamic, cumulative and temporal reality of BC care trajectories and their related adverse effects to help vulnerable patients in their RTW process. Main implications: This study emphasized the necessity to consider the holistic and sequential aspect of BC care trajectory and its related-adverse events to better target and help vulnerable BC patients in their RTW process.