Sex-steroid hormones, gonadotropin and ovarian carcinogenesis: a review of epidemiological and experimental data

Epithelial ovarian cancer is the among the five leading sites for cancer incidence and mortality in women from developed countries(1). This malignancy ranges widely in frequency among different geographic areas and ethnic groups, with a high incidence in Northern Europe and the USA and a low incidence in Japan(2). Approximately 70% of the cases are at an advanced stage at presentation because of the absence of specific symptoms and signs and the lack of reliable methods for screening. Tumor stage is the most important prognostic factor(3-5). Annual Report No. 24 of the International Federation of Gynecology and Obstetrics (FIGO) reported 5-year survival rates ranging from 89.9% for stage Ia to 28.7% for stage IIIc to 16.8% for stage IV3. As for advanced disease, residual tumor after initial surgery is the strongest prognostic variable(2-4),(6),(7). Among the patients with stage IIIc ovarian cancer analyzed by Annual Report No. 24, 5-year survival was 55% for patients with no macroscopic residumn, 42.3% for those with macroscopic residuum < 2 cm and 15.2% for those with bulkier residual disease(3). Although the parameters defining 'optimal' cytoreduction continue to evolve, complete resection to no visible residual disease is associated with the best overall survival(7). Cytoreductive surgery followed by paclitaxel/platinum-based chemotherapy represents the standard treatment for advanced epithelial ovarian cancer. Current regimens are able to obtain a complete clinical response rate of approximately 50%, a complete pathological response rate of 25-30%, a median progression-free survival of 15.5-22 months, and a median overall survival of 31-44 months(8-13).