Estrogens and epithelial ovarian cancer

Objective. Molecular mechanisms involved in ovarian carcinogenesis are still unclear, but there is growing evidence that estrogens promote tumor progression in an epithelia] ovarian cancer (EOC) subgroup. Methods. We reviewed current knowledge on the effects of estrogens in ovarian carcinogenesis and new potential research focuses concerning hormonal therapy of EOC. Results. Experimentally, estrogen stimulates the growth of ovarian tumor cell lines expressing estrogen receptors (ER). We and other authors have demonstrated differential expression of ERalpha or beta during ovarian carcinogenesis, with overexpression of ERalpha as compared to ER in cancer. This differential expression in ER suggests that estrogen-induced proteins may act as ovarian tumor-promoting agents. Among these proteins, c-myc, fibulin-1, cathepsin-D, or several kallikreins may play a role, since high expression levels have been found in EOC. Consistently, recent prospective epidemiological studies have indicated that estrogen replacement therapy in postmenopausal women may increase ovarian cancer incidence and mortality. Conclusion. Questions on the estrogen-sensitivity and potential benefits of new hormone therapies in an EOC subgroup should be readdressed in the light of recent experimental and clinical data. (C) 2004 Elsevier Inc. All rights reserved.