Background: The increased survival of breast cancer (BC) patients by earlier detection and improved treatment outcomes together with younger age at diagnosis, raised the concerns about Quality of Life among survivors, suffering from treatment side effects. Objectives: To measure QOL among BC Egyptian females, then to compare HRQOL scores in BC patients receiving different lines of treatment. Methods: A comparative cross-sectional study on a sample 142 BC survivor receiving different lines of treatment, using EORTC QLQ-C30, and a BC-specific scale (QLQBR23 scale). Results: The emotional functioning had the lowest score (29.22±8.1), the most prominent symptom was appetite loss (69.48±15.6) and in QLQ-BC23 scale, the future perspectives had the lowest score among functioning scale (19.71±4.9). While among the symptoms scale; the most annoying symptom was upset by hair loss (89.67±15.5). A significant difference in emotional subscale between three lines of treatment (p=0.000) with the hormone therapy had the highest Global QOL (41.17±9.97) (p=0.008). Significant inverse correlation between the level of Global QOL and presence of chronic disease in the chemotherapy group (p=0.001) and stage of carcinoma in all lines of treatment. Moreover, the results proved that age and stage of carcinoma were the significant predictors for Global QOL. Conclusion: Hormonal therapy group showed the best functional scale in all subdomains of QLQ-C30 and QLQ-BC23, while radiotherapy group showed the lowest scores in QOL-C30 and chemotherapy group in QLQ-BC23. Chemotherapy group shows the highest level of problematic Global QOL with appetite loss in QLQ-C30 and upset from hair loss in QLQ-BC23.