Hormonal interactions in endometrial cancer

Endometrial cancer (EC) is the most frequent malignant tumor of the female genital tract. Increasing evidence suggests that at least two different types of EC exist. Type I is associated with an endocrine milieu of estrogen predominance. These tumors are of endometrioid histology and develop from endometrial hyperplasia. They have a good prognosis and are sensitive to endocrine manipulation. Type II EC is not associated with a history of unopposed estrogens and develops from the atrophic endometrium of elderly women. They are of serous histology, have a poor prognosis, and do not react to endocrine manipulation. Both types of EC probably differ markedly with regard to the molecular mechanisms of malignant transformation. This article reviews reproductive and lifestyle factors modifying the risk of developing type I EC, including the use of hormonal contraceptives, hormone replacement therapy and tamoxifen. The roles of established and novel therapies for precancerous lesions and for invasive EC in the adjuvant and palliative settings are discussed.