Overview and Risk Factors
Ovarian cancer is the second most common gynecologic cancer (after cervical cancer) and the leading cause of death from gynecologic cancer in the United States. It generally affects women aged 40 to 65.
The ovary is composed of epithelial cells (along the surface), germ (egg-producing) cells, and sex cord stroma (connective tissue surrounding the ovary). These cell types, each of which has the potential for malignant transformation, constitute the main types of primary ovarian cancer. In addition, metastatic breast and gastrointestinal cancers commonly affect the ovaries. The most common ovarian malignancy is epithelial carcinoma (approximately 90% of cases), which is the focus of this chapter.
In the early stages, ovarian cancer usually exhibits subtle and nonspecific symptoms that rarely prompt a woman to seek medical attention. More severe symptoms caused by ovarian torsion or rupture are rare. As a result, only about 20% of cases are diagnosed at an early stage.
Nonspecific symptoms may include:
- Anorexia and fatigue.
- Low abdominal discomfort (eg, pressure, swelling, cramps, bloating, flatus).
- Low back pain.
- Early satiety and maldigestion.
- Nausea, diarrhea, and constipation.
- Frequent urination.
- Weight gain or loss.
- Irregular or abnormal vaginal bleeding, and dyspareunia.
- Unilateral or bilateral lower extremity edema.
Possible risk factors are listed below, although the exact mechanism of induction or protection in ovarian cancer is not clearly understood.
Nulliparity or infertility.
Age. Most ovarian cancers occur in women over 50 years, with the highest risk for those over 60.
Family history. Women who have relatives with ovarian cancer have an approximately 3-fold increased risk, with multiple affected relatives raising the risk further.
BRCA gene mutation. Women with a BRCA1 or BRCA2 mutation have a 25% to 45% lifetime risk of ovarian malignancy, with BRCA1 generally presenting a higher risk.
Race. White women have higher rates of ovarian cancer than black women.1
Previous cancer. Women with a history of breast or colon cancer may have an increased risk.
Diet. See Nutritional Considerations.
In addition, estrogen-replacement therapy, smoking, and obesity may be risk factors. Breast-feeding, previous pregnancy (and especially multiparity), oral contraceptive use, tubal ligation, and hysterectomy may reduce risk for ovarian cancer.
Diagnosis and Treatment
A careful history may reveal frequent, multiple symptoms with a relatively acute onset and severity, but is unlikely to distinguish between benign and malignant disease.
Physical examination may reveal no pertinent findings, as an early tumor is often not palpable. However, as the tumor enlarges, physical examination may reveal a lower abdominal mass. Pelvic examination may reveal an asymptomatic, irregular, and fixed adnexal mass. Although not pathognomonic for ovarian cancer, especially in premenopausal women, a pelvic or abdominal mass should prompt further evaluation through imaging and/or laboratory analysis.
Ultrasound helps to distinguish benign from malignant masses. In general, most women should have surgery to determine a histologic diagnosis. In cases where ultrasonography reveals an apparently benign mass, continued observation may be prudent. Ultrasound may also serve as an annual screening tool in women with the BRCA gene mutation.
CT scan and MRI are not helpful for the diagnosis of a known pelvic mass, but they may reveal extra-ovarian primary tumors or serve to quantify the extent of metastases in presumed ovarian cancer prior to surgery.
Tumor markers, such as CA-125, are not helpful for screening or diagnosis because they can be elevated in benign conditions (eg, endometriosis), particularly in premenopausal women, and also for nonovarian malignancies. CA-125 is also not always positive in early stages of ovarian cancer. However, in postmenopausal women, the test has a positive predictive value of 97%.2 The CA-125 marker is used to monitor treatment of ovarian cancer, comparing presurgery and posttreatment levels.
The preferred treatment depends on histology and surgical tumor staging:
Stage I is limited to the ovary or ovaries.
Stage II includes pelvic extension.
Stage III includes extra-pelvic peritoneal spread and/or inguinal or retroperitoneal lymph node involvement.
Stage IV involves distant metastases.
In early stages, treatment involves surgical resection, along with abdominal hysterectomy, bilateral salpingo-oophorectomy, omentectomy, and selective lymphadenectomy. With more advanced disease, surgical removal and postoperative chemotherapy are indicated.
Epidemiologic investigations have revealed important clues to etiological factors in ovarian cancer. Mortality in both the Mediterranean region4 and Asia5 is associated with consumption of meat, milk, and animal fat. In contrast, women whose diets are rich in fruits and vegetables appear to have a reduced risk, as described below. These associations have not been tested in randomized clinical trials for ethical and practical reasons. Nonetheless, they suggest important hypotheses regarding means to reduce cancer risk:
Diet and Prevention of Ovarian Cancer
The following factors are under investigation for a possible role in reducing ovarian cancer risk:
Avoiding or reducing meat and saturated fat. A high intake of fat is associated with an increase in risk for ovarian cancer of about 25%, and most of this risk is attributed to saturated fat intake.6 Various food sources of saturated fat have been implicated, including meat,7-8 eggs,9 and whole milk.10 Animal fat and meat influence estrogen activity and increase blood concentrations of insulin-like growth factor-1 (IGF-1),11 a hormone implicated in several cancers, including ovarian cancer.12
Avoiding milk. Saturated fat aside, even consumers of skim or low-fat milk in small amounts (one or more servings per day) have a greater risk for ovarian cancer, which has been attributed to galactose-related oocyte toxicity and/or elevation of gonadotropin concentrations.13,14 Milk consumption also elevates IGF-1 blood concentrations. Some researchers have suggested this is due to the fact that cow's milk contains IGF-1 that is identical to the growth factor produced by humans.15 However, milk's macronutrients also stimulate IGF-1 production within the human body.
Increased fruit and vegetable intake. Some evidence suggests that the benefit of higher fruit and vegetable intake on ovarian cancer risk is evident only in women with higher intake during adolescence.16 Other studies found that the benefit is limited to women eating 3 or more vegetable servings per day, estimating a 39% lower risk for ovarian cancer compared with women eating 1 or fewer servings per day.14 This benefit may be attributable to certain carotenoids, such as beta-carotene17 and lutein.18 The strong protective effect of green leafy vegetables19 may be attributable to folate.20
Intake of foods rich in vitamin E. Higher intake of food sources of vitamin E, including whole grains, wheat germ, and nuts, is associated with a 40% lower risk for ovarian cancer.21,22 Some evidence indicates that supplementary vitamin E (>75 mg/day) is associated with lower risk,23 although others found that this benefit is evident only with long-term (> 10 years) supplementation.24
Avoidance of obesity. Obesity in adolescence or early adulthood increases later risk for ovarian cancer by 1.5 to 2.0 times that of women with normal body mass index (BMI).25,26
Moderate alcohol intake. Alcohol-containing beverages do not appear to increase the risk for ovarian cancer.27 Evidence indicates that alcohol intake may even be protective against this cancer, provided that folate intake is fairly high (≥331 μg per day). This statistical association is not a reason to initiate or maintain alcohol consumption, however. Alcohol contributes to risk of breast cancer and other conditions.
Diet and Survival after Ovarian Cancer Diagnosis
The preceding studies relate to risk of developing ovarian cancer. However, some studies also suggest that diet may also play a role after diagnosis. The following foods are under study:
Vegetables. Women with ovarian cancer who consume vegetable-rich diets tend to have enhanced survival. In a population-based, case-controlled study, women who consumed the most vegetables had a 25% lower mortality risk, compared with women consuming the least. A similar association was found in these women for the intake of cruciferous vegetables (including broccoli, cauliflower, and cabbage), and survival was inversely associated with intake of red meat, white meat, and total protein.29
Green tea. Drinking green tea is associated with a lower risk for developing ovarian cancer.30 Drinking 1 cup or more per day was associated with a 57% lower mortality risk in women with ovarian cancer.31 Although green tea is known to inhibit cancer growth through a variety of mechanisms in vitroand in vivo,32 further study is needed to assess the benefit of green tea in survival of ovarian cancer.
Weight loss, as appropriate. See Obesity chapter
What to Tell the Family
Risk of developing ovarian cancer or of succumbing to it may be reduced through healthy diet and lifestyle practices, along with timely screening and early intervention. Family members may support the patient and improve their own health by adopting the same changes. Smoking cessation, maintaining a healthy weight, and breastfeeding all should be encouraged to reduce the risk of ovarian cancer, in addition to their other health benefits.
1. Mink PJ, Sherman ME, Devesa SS. Incidence patterns of invasive and borderline ovarian tumors among white women and black women in the United States. Cancer. 2002;95:2380-2389.
2. American College of Obstetricians and Gynecologists. ACOG Committee Opinion Number 280: The role of the generalist obstetrician-gynecologist in the early detection of ovarian cancer. Obstet Gynecol. 2002; 100:1413-1416.
3. American Joint Committee on Cancer. AJCC Cancer Staging Manual. 6th ed. New York, NY: Springer-Verlag; 2002.
4. Serra-Majem L, La Vecchia C, Ribas-Barba L, et al. Changes in diet and mortality from selected cancers in southern Mediterranean countries, 1960-1989. Eur J Clin Nutr. 1993;47(suppl 1):S25-S34.
5. Kato I, Tominaga S, Kuroishi T. Relationship between westernization of dietary habits and mortality from breast and ovarian cancers in Japan. Jpn J Cancer Res. 1987;78:349-357.
6. Huncharek M, Kupelnick B. Dietary fat intake and risk of epithelial ovarian cancer: a meta-analysis of 6,689 subjects from 8 observational studies. Nutr Cancer. 2001;40:87-91.
7. Mori M, Miyake H. Dietary and other risk factors of ovarian cancer among elderly women. Jpn J Cancer Res. 1988;79:997-1004.
8. La Vecchia C, Decarli A, Negri E, et al. Dietary factors and the risk of epithelial ovarian cancer. J Natl Cancer Inst. 1987;79:663-669.
9. Risch HA, Jain M, Marrett LD, Howe GR. Dietary fat intake and risk of epithelial ovarian cancer. J Natl Cancer Inst. 1994;86:1409-1415.
10. Mettlin CJ, Piver MS. A case-control study of milk-drinking and ovarian cancer risk. Am J Epidemiol. 1990;132:871-876.
11. Heald AH, Cade JE, Cruickshank JK, Anderson S, White A, Gibson JM. The influence of dietary intake on the insulin-like growth factor (IGF) system across three ethnic groups: a population-based study. Public Health Nutr. 2003;6:175-180.
12. Druckmann R, Rohr UD. IGF-1 in gynecology and obstetrics: update 2002.
Maturitas. 2002;41(suppl 1):S65-S83.
13. Fairfield KM, Hunter DJ, Colditz GA, et al. A prospective study of dietary lactose and ovarian cancer. Int J Cancer. 2004;110:271-277.
14. Larsson SC, Bergkvist L, Wolk A. Milk and lactose intakes and ovarian cancer risk in the Swedish Mammography Cohort. Am J Clin Nutr. 2004;80:1353-1357.
15. Allen NE, Appleby PN, Davey GK, Kaaks R, Rinaldi S, Key TJ. The associations of diet with serum insulin-like growth factor I and its main binding proteins in 292 women meat-eaters, vegetarians, and vegans. Cancer Epidemiol Biomarkers Prev. 2002;11:1441-1448.
16. Fairfield KM, Hankinson SE, Rosner BA, Hunter DJ, Colditz GA, Willett WC. Risk of ovarian carcinoma and consumption of vitamins A, C, and E and specific carotenoids: a prospective analysis. Cancer. 2001;92:2318-2326.
17. Huncharek M, Klassen H, Kupelnick B. Dietary beta-carotene intake and the risk of epithelial ovarian cancer: a meta-analysis of 3,782 subjects from five observational studies. In Vivo. 2001;15:339-343.
18. Bertone ER, Hankinson SE, Newcomb PA, et al. A population-based case-control study of carotenoid and vitamin A intake and ovarian cancer (United States). Cancer Causes Control. 2001;12:83-90.
19. Kushi LH, Mink PJ, Folsom AR, et al. Prospective study of diet and ovarian cancer. Am J Epidemiol. 1999;149:21-31.
20. Larsson SC, Giovannucci E, Wolk A. Dietary folate intake and incidence of ovarian cancer: the Swedish Mammography Cohort. J Natl Cancer Inst. 2004;96:396-402.
21. Bidoli E, La Vecchia C, Talamini R, et al. Micronutrients and ovarian cancer: a case-control study in Italy. Ann Oncol. 2001;12:1589-1593.
22. McCann SE, Moysich KB, Mettlin C. Intakes of selected nutrients and food groups and risk of ovarian cancer. Nutr Cancer. 2001;39:19-28.
23. Fleischauer AT, Olson SH, Mignone L, Simonsen N, Caputo TA, Harlap S. Dietary antioxidants, supplements, and risk of epithelial ovarian cancer. Nutr Cancer. 2001;40:92-98.
24. Pan SY, Ugnat AM, Mao Y, Wen SW, Johnson KC, and the Canadian Cancer Registries Epidemiology Research Group. A case-control study of diet and the risk of ovarian cancer. Cancer Epidemiol Biomarkers Prev. 2004;13:1521-1527.
25. Engeland A, Tretli S, Bjorge T. Height, body mass index, and ovarian cancer: a follow-up of 1.1 million Norwegian women. J Natl Cancer Inst. 2003;95:1244-1248.
28. Kelemen LE, Sellers TA, Vierkant RA, Harnack L, Cerhan JR. Association of folate and alcohol with risk of ovarian cancer in a prospective study of postmenopausal women. Cancer Causes Control. 2004;15:1085-1093.
29. Nagle CM, Purdie DM, Webb PM, Green A, Harvey PW, Bain CJ. Dietary influences on survival after ovarian cancer. Int J Cancer. 2003;106:264-269.
30. Zhang M, Binns CW, Lee AH. Tea consumption and ovarian cancer risk: a case-control study in China. Cancer Epidemiol Biomarkers Prev. 2002;11:713-718.
31. Zhang M, Lee AH, Binns CW, Xie X. Green tea consumption enhances survival of epithelial ovarian cancer. Int J Cancer. 2004;112:465-469.
32. Chung FL, Schwartz J, Herzog CR, Yang YM. Tea and cancer prevention: studies in animals and humans. J Nutr. 2003;133:3268S-3274S.