Ovarian cancer remains the most lethal of gynecologic malignancies in developed countries. Initial management is aimed at maximal cytoreduction by surgery either before or after chemotherapy. Sequential palliative chemotherapy has enabled women to live with recurrent disease for years before suffering and dying with bowel obstruction. Despite advances, effective screening and cure remains elusive for most women.
Epithelial cancer of the ovary is the fifth most common tumor of women in the United States after cancer of the breast, colon, lung, and endometrium. It is the most lethal gynecologic malignancy, with approximately 22,240 cases and 14,030 deaths each year (1, 2). One in 70 of American women will develop ovarian cancer sometime during their lifetime. In premenopausal women ovarian cancer is uncommon and found in less than 5% of adnexal masses; indeed, only 30% of adnexal masses are malignant in postmenopausal women.
EPIDEMIOLOGY OF EPITHELIAL OVARIAN CANCER
The majority of ovarian cancer presents in postmenopausal women with only 10%–15% of cancers occurring in premenopausal patients. Median age at diagnosis is reported between 60 and 65 years. Possible risk factors identified in case controlled studies include white race, nulliparity, infertility, high fat diet, lactose, paracetamol, and asbestos contaminated talc. Oral contraceptives, pregnancy, tubal ligation, and lactation reduce the risk. The association with early menarche, late menopause, and nulliparity suggests that uninterrupted "incessant" ovulation may predispose to malignancy. The oral contraceptive pill may offer some protective benefit in preventing ovarian cancer in high-risk populations. However, hormone replacement therapy appears to double the risk of death from ovarian cancer. Initial reports of increased risks from fertility drugs have not been confirmed.
The vast majority of ovarian cancer is sporadic. However, a family history of ovarian cancer increases the risk of developing ovarian cancer two- to threefold, and it is estimated that 5%–15% of all epithelial ovarian cancer cases result from inherited predisposition. Approximately 75% of these families are linked to the breast ovarian cancer syndrome with loss of function of the tumor suppressor genes BRCA1 and BRCA2, involved in DNA repair, and inherited in an autosomally dominant fashion. Hereditary breast-ovarian cancer syndrome (HBOC) accounts for 65%–75% of all hereditary ovarian cancer cases, and is defined variably but typically with at least three cases of early onset (<60 years) breast or ovarian cancer. Mutations in BRCA1 (located on chromosome 17q) and BRCA2 (13q) are associated with a 40%–60% lifetime risk of ovarian cancer. The founder mutations 185delAG, and 5382insC in BRCA1, and 6174delT in BRCA2 are present in 2.5% of Ashkenazi women.
Hereditary non-polyposis colon cancer syndrome (HNPCC, Lynch syndrome [type II]) results from mismatch repair (MSH2, MLH1, and PMS2) gene defects, low penetrance allele, and modifier gene defects. The American founder mutation is deletion of exons 1–6 of MSH2. HNPCC accounts for approximately 10%–15% of all hereditary ovarian cancer cases. A diagnosis of HNPCC can be made using the Amsterdam Criteria (colon cancer diagnosis in ≥3 relatives, one of whom is a first-degree relative of the other two, and one diagnosis before age 50 years). The risk of ...