Objective: The aim of current study was to evaluate the changes of health-related quality of life (HRQoL) and its clinical, demographic and socioeconomic determinants during chemotherapy and 4 months follow-up in women with breast cancer using a repeated measures framework. Methods and Materials: A double blind cohort study was performed in 100 breast cancer patients given fluorouracil, doxorubicin and cyclophosphamide (FAC) or docetaxel, doxorubicin, cyclophosphamide (TAC) in south of Iran. HRQoL was assessed at baseline, end of chemotherapy and four months thereafter using the QLQ-C30 questionnaire from European Organization for Research and Treatment of Cancer (EORTC). Generalized estimating equations (GEE) was applied for statistical analysis. Results: The mean of age at baseline was $48.5{pm}10.6$. 70% and 14% of patients were married and smokers, respectively, and 20% suffered from another disease besides breast cancer. The results of GEE showed that after control for baseline scores, the HRQoL significantly improved over time. Although, the patients in FAC group had higher scores than the TAC group, the differences also diminished over time. Smoking, marital status and having child affected some scales of HRQoL. None of other variables were significantly related to HRQoL. Conclusion: Although patients in TAC groups had lower level of HRQoL over 8 months follow up, they experienced faster improvement than the FAC group. This implies that in long-term, improvements in TAC group are higher than FAC. Having children was positively correlated with HRQoL. Generally, there were no demographic and socio-economic differences in HRQoL in these patients between the chemotherapeutic regimens.