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Background: Hormones and genetics play a critical role in breast cancer development, determining the association between plasma hormones and breast cancer risk among familial and non-familial females may provide insight into the etiology of breast cancer. Material and Methods: 140 postmenopausal females during the period between June 2007 and May 2011 were enrolled in this study, 83 were breast cancer patients and 57 were benign patients. Plasma estradiol, progesterone and prolactin levels were estimated among familial and non-familial breast cancer females. Estrogen and progesterone receptor status was determined for all breast cancer and benign females. Results: 20% of non-familial breast cancer and 16% of benign females have abnormal prolactin. 4% of non-familial breast cancer and 12% of benign females have abnormal progesterone. On the other hand, 57% of non-familial breast cancer females and 44% of non-familial benign females have abnormal serum estradiol. Plasma levels of estradiol were significantly associated with benign and breast cancer risk among both familial and non-familial females. While plasma levels of prolactin were significantly associated with breast cancer risk among non-familial females. Positive estrogen and progesterone receptors associated with increased benign or breast cancer risk among non-familial with high estradiol levels. Conclusion: Abnormal plasma estradiol and positive estrogen and progesterone receptors associated with increased risk among postmenopausal both among non familial benign and breast cancer females. These findings suggest that estradiol, prolactin and estrogen and progesterone receptors evaluation might be useful to better identify females with non-familial hormone-dependent disease that should be considered in breast cancer pathogenesis as well as in the treatments.