Abstract CN02-03: Prospects for targeted reduction of ovarian cancer risk

Abstract

Abstract CN02-03 The 5 year survival for patients diagnosed with Stage 3 and 4 epithelial ovarian cancer (EOC) is less than 40% in spite of overall benefit from primary treatment with debulking surgery and chemotherapy. For advanced EOC, even clinical complete responses are usually time-limited, a situation that supports a strategy for earlier intervention. Efforts to establish a screening program with ultrasound and CA-125 have been encumbered by false positive results. The absence of demonstrated benefit in a definitive trial precludes the implementation of widespread screening in the general population. For high risk women like those with BRCA or HNPCC mutations, prophylactic salpingo-oophorectomy is available for risk reduction. Otherwise, the identification of specific risk markers and precursor lesions in the general population remains a challenging goal for EOC prevention research. Because access to human tissues of interest is limited, many questions about the natural history of EOC remain to be answered, and translational efforts have focused on preclinical models and animal studies. In spite of the difficulties, there are promising leads and methodology that can be pursued to make ovarian cancer risk reduction a broader reality. From epidemiologic studies, a major result in risk modification is the association of oral contraceptive use with EOC risk reduction. The literature is replete with studies that also link EOC with a variety of other hormonal and reproductive factors. These results have been used to support a number of etiologic hypotheses including risk related to 1) incessant ovulation, 2) gonadotropins, 3) hormones (estrogen/androgen/progesterone, and 4) inflammation. These hypotheses are interrelated and support a systems biology approach that integrates changes in the tumor microenvironment along with changes in the epithelium to identify targeted opportunities for preventive modulation. At this point, the translational research process may be well served by small clinical trials that are carefully designed to reconcile inconsistencies in existing data and to test mechanistic leads from preclinical studies as well as from investigations with therapeutics like bevacizumab and anti-Mullerian hormone. Pathways of interest include those related to aromatase and prostaglandins. With specific targets in mind, biomarker comparison in controls using placebo versus subjects using chemopreventive agents as mechanistic probes should allow an improved definition of risk and response. Citation Information: Cancer Prev Res 2008;1(7 Suppl):CN02-03.