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Although the incidence of ovarian cancer is relatively low, it has very few clinical symptoms early in its course. Thus, ovarian cancer is usually discovered late at a metastatic state. Unfortunately, screening the general population may not be efficacious with currently available tests.18,19 Presently, the lifetime risk for developing ovarian cancer is 1 in 70 (1.4%) for the general American female population, with an average age at diagnosis of 57. However, close evaluation of women who are identified to be "at risk" will improve the efficacy of screening schemes (Table 35-2). More recent estimates indicate that the lifetime risk for developing ovarian cancer is now up to 1 in 55 (1.8%) for the general worldwide population. In comparison, risk factors such as nulliparity, perineal talc exposure, infertility, high-fat diet, and previous breast cancer each confer a 2.0% lifetime risk. A family history of ovarian cancer also increases risk. Ovarian cancer in 1 second-degree relative increases a woman's lifetime risk to 2.9%; 1 first-degree relative increases risk to 4.5%; and history of 2 first-degree relatives with ovarian cancer confers a lifetime risk of 39% (see Table 35-2).19 Despite the greatly increased risk associated with family history of ovarian cancer, the vast majority (>90%) of ovarian cancers occur in women without a family history or known predisposing factor.
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Ovarian cancer syndromes represent fewer than 10% of all ovarian cancers and can be subdivided into 3 general categories: cancer limited to the ovaries, breast–ovarian, and multiple site (Lynch type II: ovarian, proximal colon, and endometrial cancers, Li-Fraumeni syndrome, and Cowden syndrome). Women with one of these syndromes tend to be diagnosed with ovarian cancer at an earlier age (median 47 years, with 20% occurring before age 40) than the general population (median 57 years).
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Recently, it has been recognized that genetics play an important role in the identification of women at risk for ovarian cancer.20,21,22,23 It has been estimated that 40% to 60% of ovarian cancers are associated with malfunction of p53, a protein responsible for tumor growth inhibition.24 As a result of mutations in the p53 gene, tumor suppression pathways malfunction, thus leading to the development of tumors. The most recent advancement in genetic testing to identify women at risk for developing breast and ovarian cancer is analysis of the BReast CAncer (BRCA) gene on the long arm of chromosome 17. The presence of one of 2 gene mutations at this locus (BRCA1 and BRCA2) confers a 30% risk of ovarian cancer by the age of 60.22 Loss of heterogeneity in the BRCA gene has been identified in up to 70% of sporadically occurring ovarian cancers. A high incidence of this gene mutation has been shown to be present in a group of Israeli women (Ashkenazi Jews) with ovarian cancer.23
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Serum tests have also been suggested as a method to identify high-risk women who would benefit from early detection of ovarian cancer. CA-125 is an antigen that can be detected in serum and is associated with malignancies such as ovarian cancer. However, CA-125 has a relatively limited sensitivity and specificity. Only 47% of Federation of Gynecologists and Obstetricians (FIGO) stage I ovarian cancers were positive for CA-125 in one large series. Furthermore, elevated levels of this glycoprotein can be seen in a variety of disorders, especially in the premenopausal age group. CA-125 is, however, an accurate means by which patients may be followed for detection of recurrent disease.25
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There have been several recent developments in serum biomarker tests, including the use of proteomics and multianalyte screening. Proteomic assays involve mass spectroscopy of certain serum proteins and gene products and is reported to be highly accurate.5 One study of 50 women with known ovarian cancer and 66 women with nonovarian cancer pathology reported a sensitivity of 100% and specificity of 99% for the proteomic assay (positive predictive value 94%).5 Another serum assay for a panel of 4 analytes (leptin, prolactin, osteopontin, and insulin-like growth factor) in 106 controls and 100 women with ovarian cancer reported a sensitivity of 95%, specificity of 95%, positive predictive value of 95%, and negative predictive value of 94%.6 Although neither of these tests is currently clinically available, there is great potential for the combination of serum analysis with sonographic imaging in the formulation of a multimodal screening scheme.
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Risk factors for endometrial cancers include obesity, low parity, diabetes, and hypertension. Endometrial cancer differs from ovarian cancer, however, in that most endometrial cancers become symptomatic before significant intramyometrial spread occurs. In one study of mass screening for endometrial cancers in asymptomatic women, a high incidence (6.3%) of pre-invasive cancers was found in diabetic women. In comparison, the incidence of preclinical endometrial cancer in a population of hypertensive women was 1.3%.21 Although many women with endometrial cancer will present with postmenopausal bleeding, the corollary is not true; only 10% to 15% of women with postmenopausal bleeding are eventually found to have endometrial cancer. Transvaginal sonography therefore plays a pivotal diagnostic role in distinguishing those patients needing biopsy from those who would be best observed or treated medically.