Abstract Background: Breast cancer (BC) is the most common malignancy and the leading cause of cancer-related deaths among young women worldwide. This population usually presents with more advanced stages at diagnosis compared to their older counterparts, exposing them to more intensive treatments which compromise their quality of life (QOL). This study aims to determine the change in QOL in young women with locally-advanced BC over time. Methods: Women aged ≤40, newly diagnosed with locally-advanced BC from 2016 to 2020 at three cancer referral centers in Mexico and accrued in the Joven & Fuerte cohort were included and asked to complete the EORTC QLQ-C30 and QLQ-BR23 questionnaires at diagnosis, six months, and one year follow-up. Differences in mean values were analyzed using repeated measures ANOVA tests. The Mauchly's test was employed to assess the assumption of sphericity and if violated the Huynh-Feldt correction was used. Adjustment of multiple comparisons was performed with the Bonferroni correction. Results: A total of 195 patients with a median age at diagnosis of 35 years (IQR: 32-38) were analyzed. Most patients (59%) were married or in a domestic partnership and the majority (60%) were housewives or unemployed. The distribution of clinical stages at diagnosis was: IIB (41%), IIIA (39%), IIIB (11%), and IIIC (10%). Regarding treatment modalities, most patients underwent mastectomy (n=111, 57%), neoadjuvant (n=103, 53%) or adjuvant chemotherapy (n=79, 41%), and adjuvant endocrine therapy (n=106, 54%). QLQ changes over time are shown in the Table. Most functional scales worsened significantly at six months. Although most of them improved at one year of follow-up, they did not reach baseline levels. Certain symptoms such as fatigue, insomnia, financial difficulties, and arm symptoms worsened from baseline. When analyzing QLQ changes according to the different treatment modalities (mastectomy vs lumpectomy), (neoadjuvant vs neoadjuvant/adjuvant vs adjuvant chemotherapy) and (receiving hormone therapy vs not) no significant differences were found in functional scales or BC symptoms over time. Conclusion: Young women with BC experience physical and psychological distress that negatively impacts their QOL. Several BC specific domains worsened from baseline, such as body imaging, sexual satisfaction, and arm symptoms. Thus, strategies aimed at addressing these specific areas are warranted. QLQ-C30 and QLQ-BR23 at baseline, six months and one yearMean (SEM)NumberBaselineSix monthsOne yearp valueQLQ-C30Global health status14277.76 (1.65)73.53 (1.81)78.46 (1.59)0.047Physical Functioning14290.09 (0.93)86.62 (1.16)89.20 (1.02)0.026Role Functioning14286.97 (1.53)80.16 (1.86)87.68 (1.37)<0.001Emotional Functioning14275.12 (1.72)75.47 (1.81)73.01 (1.89)0.419Cognitive Functioning14282.75 (1.75)76.88 (1.75)77.93 (1.78)0.012Social Functioning14284.04 (1.83)77.70 (1.98)80.40 (1.82)0.015Fatigue14223.79 (1.53)29.89 (1.61)26.21 (1.50)0.002Nausea and vomiting1428.22 (1.23)11.39 (1.49)5.87 (1.22)0.012Pain14222.18 (1.87)21.95 (1.92)21.13 (1.67)0.876Dyspnea14210.80 (1.81)14.55 (1.68)10.09 (1.37)0.085Insomnia14226.29 (2.33)30.75 (2.43)27.23 (2.28)0.278Appetite Loss1429.39 (1.35)11.50 (1.45)8.45 (1.27)0.203Constipation14216.67 (2.28)20.42 (2.23)16.43 (1.94)0.259Diarrhea1428.45 (1.39)8.45 (1.35)5.87 (1.22)0.233Financial Difficulties14232.86 (2.56)38.73 (2.55)35.92 (2.60)0.161QLQ-BR23Body Imaging14280.69 (2.05)74.77 (2.15)76.64 (2.12)0.029Sexual Functioning14231.81 (2.33)24.77 (1.97)30.16 (1.99)0.009Sexual Enjoyment6162.84 (3.90)50.82 (4.45)50.27 (3.71)0.012Future Perspective14252.35 (2.67)49.30 (2.76)54.23 (2.46)0.245Systemic Therapy Side Effects14222.64 (1.46)29.21 (1.45)17.00 (1.01)<0.001Breast Symptoms14223.65 (1.95)17.96 (1.58)22.52 (1.47)0.022Arm Symptoms14217.14 (1.52)16.12 (1.56)20.27 (1.54)0.063Upset by hair loss12922.48 (3.07)24.55 (3.10)5.17 (1.62)<0.001 Citation Format: Cynthia Villarreal-Garza, Bryan F Vaca-Cartagena, Andrea Becerril-Gaitan, Alejandra Platas, Melina Miaja, Fernanda Mesa-Chavez, Ana S Ferrigno, Alan Fonseca, Marlid Cruz-Ramos, Lucero Labra, Enrique Bargallo-Rocha, Alejandro Mohar. Quality of life in Mexican young women with locally-advanced breast cancer: A cohort study [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P4-10-20.