Hormonal imbalance in postmenopausal women makes them susceptible to various menopausal symptoms and hormonal replacement therapy (HRT) is the treatment option for them. However, various concerns are involved with this therapy due to increased risk of pulmonary embolism, stroke, coronary heart disease, and even cancer. Especially long term use of single or multiple hormones at the same time appears to be more associated with unwanted disorders. However, few of the reports say that hormonal therapy with estrogens protect women against breast cancer. While there exist wide range of studies to address this issue, genetic profile of the patient are also important prior to HRT. Certain gene profile women are more or less susceptible to cancer risk. In this review we will discuss about various genetic factors related to this issue.