Ovarian cancer is the leading cause of death from gynecologic cancer in the United States. It generally affects women aged 40-65 years. The disease occurs in 1 in 78 women; the average lifetime risk of developing ovarian cancer is 1.3%.
The ovary is composed of epithelial cells along the surface, germ (egg-producing) cells, and surrounding connective tissue. Each of these cell types has the potential for malignant transformation. In addition, breast, stomach, and colon cancers commonly metastasize to the ovaries. The most common ovarian malignancy is epithelial carcinoma (over 90% of cases), which is the focus of this chapter.
In the early stages, ovarian cancer usually causes subtle and nonspecific symptoms that rarely prompt a woman to seek medical attention. These may include fatigue, abdominal pain and bloating, urinary frequency, post-menopausal vaginal bleeding, anorexia, and early satiety. A common presentation is the finding of an adnexal mass on pelvic exam or imaging.
More advanced cases may present with a malignant pleural effusion or bowel obstruction.
Family history. Genetic predisposition is the strongest risk factor for ovarian cancer. Women who have relatives with ovarian cancer have an approximately 3-fold increased risk, with multiple affected relatives further raising the risk.
Specific hereditary cancer syndromes, including Lynch syndrome and the BRCA gene mutations, also increase ovarian cancer risk. Women with a BRCA1 or BRCA2 mutation have a 25-45% lifetime risk of ovarian malignancy, with BRCA1 generally presenting a higher risk.
While family history and inherited genetic mutations elevate ovarian cancer risk, only about 20-25 percent of women diagnosed with ovarian cancer have a hereditary tendency to develop the disease.
Age. Most ovarian cancers occur in women over 50 years, with the highest risk for those over 60.
Race. White women have higher rates of ovarian cancer than Black women.
Reproductive factors. Early menarche, late menopause, infertility, and nulliparity have all been associated with increased risk of ovarian cancer. Parity and oral contraceptive use decrease risk.
Hormone Replacement Therapy. Current and recent use of hormone replacement therapy in menopausal women is associated with increased risk of certain types of ovarian cancer—specifically, serous and endometrioid ovarian cancers, but not mucinous or clear cell types.
Diet. See Nutritional Considerations below.
Patients with signs and/or symptoms of ovarian cancer should be evaluated with pelvic imaging, typically a CT scan of the abdomen and pelvis.
If a suspicious mass is found, most women should undergo open surgical biopsy to determine a histologic diagnosis. Less commonly, the diagnosis is made from fluid obtained from thoracentesis or paracentesis, or from tissue obtained by image-guided core needle biopsy.
The preferred treatment depends on histology and surgical tumor staging, using the tumor, nodes, metastasis (TNM) classification system:
- 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, the surgical procedure is followed by postoperative chemotherapy.
Epidemiologic investigations have revealed important clues to etiological factors in ovarian cancer. Ovarian cancer mortality in the Mediterranean region and in Asia has been associated with consumption of meat, milk, and animal fat., In contrast, evidence suggests that ovarian cancer risk may be significantly reduced through higher intake of soy products and certain kinds of vegetables.
The following factors are under investigation for possible roles in reducing ovarian cancer risk:
Avoiding or reducing meat, eggs, and other sources of saturated fat. The NIH-AARP study found that women consuming the highest amount of animal fat had a 30% higher risk for ovarian cancer when compared with those in the lowest intake group. Similarly, an analysis of data from the EPIC and Netherlands Cohort studies found that a high (compared with low) intake of saturated fat was associated with an approximately 20% increase in risk for ovarian cancer. Various food sources of saturated fat have been implicated, including meat, eggs, and whole milk.,,, A meta-analysis of egg consumption found that American women in the highest intake group had a nearly 40% greater risk when compared with those eating the fewest eggs.
Animal fat and meat influence estrogen activity and increase blood concentrations of insulin-like growth factor-1 (IGF-1), a polypeptide implicated in several cancers, including ovarian cancer.,
Avoiding milk. Studies of dairy products and ovarian cancer risk have produced conflicting results and are a subject of some controversy. Although some studies have not revealed a relationship, a meta-analysis of prospective study data concluded that each glass of milk consumed daily raised the risk for ovarian cancer by 13%, on average. In addition, a pooled analysis of 12 prospective cohort studies including 553,217 women concluded that consumption of 3 dairy servings per day was associated with a 20% increased risk for this cancer, compared with 1 serving per day. More recently, a study of lactose intolerant women (i.e., women who avoid or minimize consumption of dairy products) concluded that the risk for ovarian cancer was significantly lower in these individuals than in milk consumers. In a case-control study with Black women specifically, ovarian cancer was more likely in those who drank whole milk and followed a diet high in lactose.
Dairy products are the largest source of saturated fat in the US diet. However, saturated fat may not be the only explanation for the association between dairy consumption and ovarian cancer. Even consumption of small amounts of skim or low-fat milk (1 or more servings daily) has been associated with an increased risk for ovarian cancer. This has been attributed to galactose-related oocyte toxicity and/or elevation of gonadotropin concentrations., 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. However, milk’s macronutrients also stimulate IGF-1 production within the human body, which is likely a greater contributor to blood IGF-1 concentrations than any direct effect of the IGF-1 ingested from milk.
Including soy products. A 2014 meta-analysis found that higher (compared with lower) intake of soy products is associated with a roughly 50% lower risk for ovarian cancer, while a 2016 meta-analysis estimated a 33% lower risk.,
Increased fruit and vegetable intake. The intake of higher amounts of cruciferous vegetables is inversely related to ovarian cancer incidence, with an 11% lower risk compared to those with the lowest intakes.
Diet and Survival after Ovarian Cancer Diagnosis
The Women’s Health Initiative (WHI) found that women with ovarian cancer whose diets were most healthful, based on the Healthy Eating Index (HEI-2005), had an almost 25% lower risk for all-cause mortality, when compared with those whose diets were least healthful.
Several reviews have found significantly poorer survival in women who were obese either in early adulthood or 5 years prior to diagnosis.
Genetic testing, when indicated.
See Basic Diet Orders chapter.
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 and maintenance of a healthy weight should be encouraged.
- Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016. CA Cancer J Clin. 2016;66(1):7-30. [PMID:26742998]
- Olson SH, Mignone L, Nakraseive C, et al. Symptoms of ovarian cancer. Obstet Gynecol. 2001;98(2):212-7. [PMID:11506835]
- Khoury-Collado F, Bombard AT. Hereditary breast and ovarian cancer: what the primary care physician should know. Obstet Gynecol Surv. 2004;59(7):537-42. [PMID:15199272]
- Mink PJ, Sherman ME, Devesa SS. Incidence patterns of invasive and borderline ovarian tumors among white women and black women in the United States. Results from the SEER Program, 1978-1998. Cancer. 2002;95(11):2380-9. [PMID:12436446]
- Hankinson SE, Colditz GA, Hunter DJ, et al. A prospective study of reproductive factors and risk of epithelial ovarian cancer. Cancer. 1995;76(2):284-90. [PMID:8625104]
- La Vecchia C. Ovarian cancer: epidemiology and risk factors. Eur J Cancer Prev. 2017;26(1):55-62. [PMID:26731563]
- 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:S25-34. [PMID:8269895]
- 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(4):349-57. [PMID:3108215]
- Blank MM, Wentzensen N, Murphy MA, et al. Dietary fat intake and risk of ovarian cancer in the NIH-AARP Diet and Health Study. Br J Cancer. 2012;106(3):596-602. [PMID:22223086]
- Merritt MA, Tzoulaki I, van den Brandt PA, et al. Nutrient-wide association study of 57 foods/nutrients and epithelial ovarian cancer in the European Prospective Investigation into Cancer and Nutrition study and the Netherlands Cohort Study. Am J Clin Nutr. 2016;103(1):161-7. [PMID:26607939]
- Mori M, Miyake H. Dietary and other risk factors of ovarian cancer among elderly women. Jpn J Cancer Res. 1988;79(9):997-1004. [PMID:3142839]
- La Vecchia C, Decarli A, Negri E, et al. Dietary factors and the risk of epithelial ovarian cancer. J Natl Cancer Inst. 1987;79(4):663-9. [PMID:3116309]
- Risch HA, Jain M, Marrett LD, et al. Dietary fat intake and risk of epithelial ovarian cancer. J Natl Cancer Inst. 1994;86(18):1409-15. [PMID:8072035]
- Mettlin CJ, Piver MS. A case-control study of milk-drinking and ovarian cancer risk. Am J Epidemiol. 1990;132(5):871-6. [PMID:2239901]
- Zeng ST, Guo L, Liu SK, et al. Egg consumption is associated with increased risk of ovarian cancer: Evidence from a meta-analysis of observational studies. Clin Nutr. 2015;34(4):635-41. [PMID:25108572]
- Heald AH, Cade JE, Cruickshank JK, et al. 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(2):175-80. [PMID:12675960]
- Hu J, Hu Y, Hu Y, et al. Intake of cruciferous vegetables is associated with reduced risk of ovarian cancer: a meta-analysis. Asia Pac J Clin Nutr. 2015;24(1):101-9. [PMID:25740748]
- Larsson SC, Orsini N, Wolk A. Milk, milk products and lactose intake and ovarian cancer risk: a meta-analysis of epidemiological studies. Int J Cancer. 2006;118(2):431-41. [PMID:16052536]
- Genkinger JM, Hunter DJ, Spiegelman D, et al. Dairy products and ovarian cancer: a pooled analysis of 12 cohort studies. Cancer Epidemiol Biomarkers Prev. 2006;15(2):364-72. [PMID:16492930]
- Ji J, Sundquist J, Sundquist K. Lactose intolerance and risk of lung, breast and ovarian cancers: aetiological clues from a population-based study in Sweden. Br J Cancer. 2015;112(1):149-52. [PMID:25314053]
- Qin B, Moorman PG, Alberg AJ, et al. Dairy, calcium, vitamin D and ovarian cancer risk in African-American women. Br J Cancer. 2016;115(9):1122-1130. [PMID:27632371]
- Fairfield KM, Hunter DJ, Colditz GA, et al. A prospective study of dietary lactose and ovarian cancer. Int J Cancer. 2004;110(2):271-7. [PMID:15069693]
- 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(5):1353-7. [PMID:15531686]
- Allen NE, Appleby PN, Davey GK, et al. 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(11):1441-8. [PMID:12433724]
- Qu XL, Fang Y, Zhang M, et al. Phytoestrogen intake and risk of ovarian cancer: a meta- analysis of 10 observational studies. Asian Pac J Cancer Prev. 2014;15(21):9085-91. [PMID:25422183]
- Hua X, Yu L, You R, et al. Association among Dietary Flavonoids, Flavonoid Subclasses and Ovarian Cancer Risk: A Meta-Analysis. PLoS ONE. 2016;11(3):e0151134. [PMID:26960146]
- Engeland A, Tretli S, Bjørge T. Height, body mass index, and ovarian cancer: a follow-up of 1.1 million Norwegian women. J Natl Cancer Inst. 2003;95(16):1244-8. [PMID:12928351]
- Fairfield KM, Willett WC, Rosner BA, et al. Obesity, weight gain, and ovarian cancer. Obstet Gynecol. 2002;100(2):288-96. [PMID:12151152]
- Thomson CA, E Crane T, Wertheim BC, et al. Diet quality and survival after ovarian cancer: results from the Women's Health Initiative. J Natl Cancer Inst. 2014;106(11). [PMID:25335480]
- Bae HS, Kim HJ, Hong JH, et al. Obesity and epithelial ovarian cancer survival: a systematic review and meta-analysis. J Ovarian Res. 2014;7:41. [PMID:24834130]