Abstract Objective Previous studies showed that various outcomes in patients with early breast cancer (EBC), from incidence to survival, were influenced by social factors. However, there is limited research on the socioeconomic inequalities in quality of life (QoL) after treatment for EBC, and the magnitude and changes over time of these inequalities have not been quantified. This study examines the socioeconomic inequalities in QoL and their time trends among a large cohort of patients with EBC. Methods We conducted a comprehensive longitudinal analysis using data from the prospective multicentric CANTO study (CANcer TOxicity, NCT01993498), which included participants with EBC enrolled between 2012 and 2018. QoL was assessed using the summary score of the EORTC QLQ-C30 questionnaire at the time of diagnosis and 1 and 2 years post-diagnosis. We included patients with complete QoL data at diagnosis and 2 years post-diagnosis. Analyses were conducted for three indicators of socioeconomic status separately: self-reported financial difficulties, household income and educational level. We first analyzed trajectories of QoL by socioeconomic status from diagnosis to Year 1 and Year 2. Then, social inequalities in QoL were estimated using the regression-based slope indexes of inequality (SII) and compared across the follow-up periods. The SII represents the absolute change in the QLQ-C30 summary score along the two extremes of the socioeconomic gradient, taking into account the intermediate groups and their relative sizes. The analyses were adjusted for age at diagnosis, Charlson comorbidity index, disease stage, use and type of endocrine therapy, use and type of chemotherapy, breast surgery, radiotherapy use, and lymph node management. Results In the 5915 analyzed patients, compared to those with higher socioeconomic status, those reporting a high level of financial difficulty, lower income, or lower education were younger, most often premenopausal, with comorbidities, diagnosed with stage III BC, and treated with mastectomy and axillary lymph node dissection. There were no differences between socioeconomically-defined groups concerning BC histology, grade and IHC-defined subtype. Social inequalities in QoL at baseline were statistically significant for all socioeconomic status indicators (SIIfinancial difficulties = -7.6 [-8.9;-6.2], SIIincome= -4.0 [-5.2;-2.8]) and SIIeducation= -1.9 [-3.1;-0.7]). In multivariable analyses, social inequalities significantly increased (interaction p< 0.05) in Year 1 (SIIfinancial difficulties = -11.1 [-12.8;-9.4], SIIincome= -6.5 [-8.0;-5.0] and SIIeducation= -5.0 [-6.6;-3.5]) and Year 2 (SIIfinancial difficulties = -10.7 [-12.2;-9.1], SIIincome= -6.7 [-8.0;-5.3] and SIIeducation= -4.7 [-6.1;-3.3]) suggesting a widening socioeconomic gap in QoL outcomes irrespective of pre-diagnosis health, tumor characteristics and treatment. Similar results were observed in subgroups defined by menopausal status (pre/postmenopausal) and type of systemic treatment (chemotherapy, endocrine therapy). Conclusion Our study highlights and quantifies the association of several individual socioeconomic indicators with the QoL of patients with EBC in France. The magnitude of socioeconomic inequalities in QoL increased over time after EBC diagnosis in a country with a strong welfare system and universal healthcare coverage. In the era of precision medicine, these results underscore the importance of developing interventions to improve precision care, considering the conditions in which people are born, grow, work, live and age and the wider set of forces and systems shaping the conditions of daily life. Citation Format: José Luis Sandoval, Antonio Di Meglio, Arlindo Ferreira, Maria Alice Franzoi, Fabrice André, Barbara Pistilli, Christelle Jouannaud, Marion Fournier, Philippe Rouanet, Asma Dhaini Mermeche, Paul Cottu, Sibille Everhard, Anne-Laure Martin, Silvia Stringhini, Idris Guessous, Ines Vaz Luis, Gwenn Menvielle. The magnitude and temporal variations of socioeconomic inequalities in quality of life after early breast cancer: results from the multicentric French CANTO cohort [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-09-12.