OBJECTIVES: To determine whether the association between the different dosage of hormone replacement therapy (HRT) and the incidence of breast cancer (BC) in postmenopausal women with HRT formulation.  METHODS: Patients who had at least one outpatient visit for postmenopausal syndrome (ICD-9-CM code 627) with estrogen prescription in Taiwan National Health Insurance (NHI) claims database during 1999- 2006 were identified as the study cases. There were 883,052 women identified from the dataset. The index date was defined as the date of the first menopausal visit with estrogen prescription during the study period. To identify any BC events, each case was tracked from the index date until December 31, 2006 or death, whichever came first. Women without events were censored on December 31, 2006. Survival analysis was performed to assess whether cumulative estrogen dosage and combined progesterone were independent risk factors of BC. RESULTS: A total of 5524 cases of BC were identified during the study period. Women with higher dosage of estrogen had significantly higher risk of BC than women with lower dosage (HR=2.23; p<0.0001). The risk of BC was even higher when progesterone was combined with estrogen (HR=1.08; p=0.036). Women aged 60-69 (HR=0.87, p=0.002) and >70 (HR=0.66, p<0.0001) had lower risk of BC, compared with women aged<60. Women living in the northern part of Taiwan and in areas with higher urbanization level had higher risk of BC, compared with their counterparts. CONCLUSIONS: Hormone replacement therapy in postmenopausal women seemed to be associated with an increased risk of BC.