Genomic Tests for Ovarian Cancer Detection and Management. Evidence Report/Technology Assessment Number 145

摘要

Ovarian cancer is the leading cause of cancer death from gynecologic malignancies in the United States, with an annual incidence of over 25,000 and an annual mortality of approximately 14,000. Cancer incidence increases dramatically with age. The high case-fatality rate has largely been attributed to the fact that most ovarian cancers are diagnosed in advanced stages (Stage III, where the cancer has spread beyond the pelvis to the organs of the upper abdominal cavity, and Stage IV, where the cancer has spread outside the peritoneal cavity). Stage I cancer (limited to the ovaries) has a survival rate of over 90 percent. There are five potential strategies for prevention of the morbidity and mortality from ovarian cancer. One is primary prevention through either medical or surgical therapy in the general population. Although observational studies suggest that the risk of developing ovarian cancer is reduced in women who used oral contraceptives or underwent tubal ligation, there are no prospective trials to allow estimation of the risks and benefits of these options specifically for ovarian cancer prevention. Although in theory prophylactic oophorectomy at the time of hysterectomy for other diseases should almost eliminate the chances of developing ovarian cancer, there are also no prospective studies of the benefits of this approach, and a recent decision analysis suggested that the harms in terms of other effects might outweigh the benefits. An alternative strategy for primary prevention is identifying groups of women at particularly high risk of developing ovarian cancer, and then using primary prevention strategies. Observational studies suggest that use of oral contraceptives reduces risk of ovarian cancer in women with inherited predisposition to ovarian cancer, but this has not been tested prospectively. Prophylactic oophorectomy does appear to reduce the risk of ovarian cancer in high-risk groups. Another strategy for prevention of ovarian cancer mortality is screening to detect early stage cancers, either in the general population or in high-risk groups. To date, screening using the available technologies of physical examination, ultrasound, and/or cancer antigen 125 (CA-125) has not been shown to be effective in either situation. Finally, use of targeted therapy based on the results of tests may identify subgroups of patients for whom specific therapies are likely to be effective; for example, identification of overexpression of human epidermal growth factor 2 (HER 2) in some breast cancers has led to improved survival with the use of a monoclonal antibody targeted against the receptor. To date, similar breakthroughs have not occurred in ovarian cancer. Continued developments in technology have led to rapidly expanding knowledge about genes, gene expression, and protein patterns in a variety of disease processes. Because currently available strategies for the prevention of ovarian cancer have not proven as effective as interventions targeted against other cancers in women, there has been tremendous interest in using the tools of genomics and proteomics to identify potential new markers which can be used in any of the five classes of strategies.