Despite the fact that it is highly curable if diagnosed early, ovarian cancer causes more mortality in American women each year than all other gynecologic malignancies combined. An estimated 21,550 new cases of this cancer will be diagnosed in the United States in 2009, and about 14,600 women will succumb to the disease.
Notable advances in chemotherapy and surgery over the past several decades have begun to translate into improved survival. According to American Cancer Society data, the overall 5-year survival rate from ovarian cancer has increased significantly, from 36% in the mid-1970s to 53% in the mid-1990s. Recent data from the National Cancer Institute show a similar increase in stage-specific survival. It is expected that data from the current decade, reflecting continued improvements in chemotherapy and surgery, will continue this trend.
This chapter will focus on epithelial cancers of the ovaries, which account for about 90% of ovarian malignancies.
Epidemiology
Age Ovarian cancer is primarily a disease of postmenopausal women, with the large majority of cases occurring in women between 50 and 75 years old. The incidence of ovarian cancer increases with age and peaks at a rate of 61.5 per 100,000 women in the 75–79-year-old age group.
Race The incidence of ovarian cancer appears to vary by race, although the effects of race are difficult to separate from those of environment related to culture, geography, and socioeconomic status. In the United States, the age-adjusted rate of ovarian cancer for Caucasians is estimated to be 17.9 per 100,000 population, which is significantly higher than 11.9 per 100,000 for the African-American population.
Geography There are distinct geographic variations in the incidence of ovarian cancer, with the highest rates found in industrialized countries and the lowest rates seen in underdeveloped nations. Japan, with an incidence of only about 3.0 per 100,000 population, is a notable exception to this observation. It has been postulated that geographic variations in the incidence of ovarian cancer are related, in part, to differences in family size.
Some of the highest rates are seen in women of Eastern European Jewish ancestry, who have an estimated incidence of 17.2 per 100,000 population, a probable result of the relatively high frequency of BRCA1 and BRCA2 mutations in this population.
Etiology and risk factors
The cause of epithelial ovarian cancer remains unknown. Although it now appears certain that, at the cellular level, ovarian cancer results from the accumulation of multiple discrete genetic defects, the mechanism(s) by which these defects develop have yet to be determined. Epidemiologic studies have identified a number of factors that may increase or decrease the risk of the disease. In addition, a small proportion of ovarian cancers in the United States, approximately 5%–10%, result from inherited defects in the BRCA1 gene or other genes, including BRCA2 and the hereditary nonpolyposis colorectal cancer (HNPCC) genes.
Diet It has been suggested that numerous dietary factors increase the risk of ovarian cancer, although the magnitude of the reported increase is relatively modest.
A low-fat diet may reduce the incidence of ovarian cancer among postmenopausal women.
Populations with a high dietary intake of lactose who lack the enzyme galactose-1-phosphate uridyltransferase have been reported to be at increased risk.
Conflicting reports have been published regarding the role of coffee consumption and the risk of ovarian cancer.
Environmental factors Various environmental risk factors also have been suggested.
Exposure to talc (hydrous magnesium trisilicate) used as dusting powder on diaphragms and sanitary napkins has been reported in some studies to increase the risk of ovarian cancer, although other studies have failed to find an association.
No association between exposure to ionizing radiation and the risk of ovarian cancer has been documented.
Several studies have examined the effect of viral agents, including mumps, rubella, and influenza viruses, on the risk of ovarian cancer. No clear relationship has been demonstrated.
Physical activity may decrease the risk of ovarian cancer.
Hormonal and reproductive factors In contrast to the conflicting data on dietary and environmental factors, some clear associations have been drawn between certain hormonal and reproductive factors and the risk of developing ovarian cancer.
Several analyses have documented that women with a history of low parity or involuntary infertility are at increased risk of ovarian cancer.
Tubal ligation significantly decreases the risk of ovarian cancer, as demonstrated by several epidemiologic studies.
Evidence suggests that treatment with ovulation-inducing drugs, particularly for prolonged periods, may be a risk factor, although it is difficult to separate the increased risk related to the infertility itself from the risk carried by use of ovulation-inducing agents.
Breastfeeding for long durations may decrease ovarian cancer risk.
Although the data are not consistent, some studies have shown an association between the use of postmenopausal hormone replacement and the development of ovarian cancer. Data from the Women’s Health Initiative randomized trial of estrogen plus progestin showed a slight increase in the risk of ovarian cancer in users of hormone replacement therapy, although it was not statistically significant.
Several large case-controlled studies have documented a marked protective effect of oral contraceptives against ovarian cancer. Women who have used oral contraceptives for at least several years have approximately half the risk of ovarian cancer as do nonusers, and the protective effect of oral contraceptives appears to persist for years after their discontinuation. It is estimated that the routine use of oral contraceptives may prevent nearly 2,000 cases of ovarian cancer yearly in the United States. Evidence suggests that the protective effect of oral contraceptives also applies to women carrying BRCA mutations.
