Endogenous and exogenous hormonal factors in female cancers : Studies of risk and prognosis

Abstract: Extensive evidence points to hormonal influences which play a critical role in the development and progression of breast, ovarian and endometrial or uterine cancers. These cancers share many common hormonal features, which are crucial in the etiology and subsequent development of these cancers. Exposure to estrogens and progestogens, both endogenous and exogenous during a woman s life can influence the risk of cancer in these target organs. As certain hormonal and reproductive factors affect the risk of developing these cancers, similarly, it is plausible that they would also influence tumor-defined characteristics and survival in breast, ovarian and endometrial cancers. My thesis work aims to further investigate the roles of endogenous and exogenous sex hormones on the etiology, risk and prognosis defined by tumor characteristics and survival; in breast, ovarian and endometrial cancers. These aims were investigated through the following four studies. Study I aimed to assess the impact of infertility treatment of clomiphene citrate (CC) and/or gonadotropins with causes of infertility on the incidence of breast cancer. We observed no overall increased risk for breast cancer with infertility treatment; however, women with non-ovulatory causes treated with high dose CC therapy may have an elevated risk for breast cancer. Study II investigated 5-year survival in patients with ovarian cancer according to hormone replacement therapy (HRT) use before and after diagnosis. We found that HRT-use prior to diagnosis of epithelial ovarian cancer did not affect 5-year survival, except for a possible survival advantage in serous cancers. Women using HRT after diagnosis had a better survival than never users. Study III looked at the effects of established menstrual risk factors on tumor characteristics and survival in postmenopausal breast cancer. We found an earlier age at menarche to have a significant impact on breast cancer prognosis and survival. Finally, Study IV looked at the influence of menopausal hormone therapy (MHT) on tumor characteristics and relative survival in postmenopausal endometrial cancer. The findings indicated that users of MHT had a better survival than non-users. The findings of these studies add new evidence in understanding the etiological mechanisms by which carcinogenesis may act to affect these cancers. What is clear from these findings is that these mechanisms are multifarious and complex and that no simple association exists between hormonal exposures and female cancers, since the influence appears contradictory for the incidence of the cancer and prognosis of the cancer. These patterns indicate the mosaic of mechanisms involved