Ovarian cancer is the leading cause of death from gynecologic cancer in the United States, with a roughly 50% 5-year survival rate. It is the third most common gynecological malignancy and the most lethal worldwide. Most patients are diagnosed with advanced disease, which carries significant mortality.[1] It generally affects women aged 40-65 years.[2]
The ovary is composed of a monolayer of modified mesothelium (ovarian surface epithelium), germ (egg-producing) cells, and surrounding connective tissue with stromal cells. 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 (more than 90% of cases), which is the focus of this chapter. Most tumors appear to originate from other gynecological tissues and involve the ovary secondarily. Compelling data suggest high- and low-grade serous neoplasms originate from fallopian tube epithelium.[1]
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, anorexia, and early satiety.[3] A common presentation is the finding of an adnexal mass on pelvic exam or imaging.[4] But this is often an advanced stage.
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 18-40% lifetime risk of ovarian malignancy, with BRCA1 generally presenting a higher risk.[5]
While family history and inherited genetic mutations elevate ovarian cancer risk, the vast majority of women diagnosed with ovarian cancer do not 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.[2]
Race. In the US, ovarian cancer incidence is higher among White women than Black women.[6]
Reproductive factors. Early menarche, late menopause, infertility, and nulliparity have all been associated with increased risk of ovarian cancer.[7] The “incessant ovulation” hypothesis posits that the number of ovulatory cycles increases the rate of cellular division associated with the repair of surface epithelium after each ovulation, thereby increasing spontaneous mutations.[8] Parity and oral contraceptive use decrease risk.[9]
Hormone replacement therapy. Current and recent use of hormone replacement therapy in menopausal women is associated with increased risk of serous and endometrioid ovarian cancers.[9] However, the epidemiological literature over the past several decades has consistently reported that use of oral contraceptives is inversely associated with the risk of ovarian cancer. The protective effect increases with longer duration of use, with about 20% decreased risk for each 5 years of use, an effect that persists decades after use has ceased.[10]
Avoidance of obesity. Obesity in adolescence or early adulthood increases later risk for ovarian cancer by 1.5-2 times, compared with women with normal body mass index.[11][12]
Diet. See Nutritional Considerations below.
Women with suspected ovarian cancer based on clinical presentation or a pelvic mass should undergo transvaginal ultrasonography, which can assess ovarian architecture and vascularity, differentiate cystic from solid masses, and detect ascites.[13][14][15]
Often women have abdominal ascites fluid, which can be analyzed with a paracentesis. Ovarian carcinomas may shed into the fluid. Alternatively, depending on the imaging characteristics, if a suspicious mass is found, the patient may have a diagnostic laparoscopy.
The preferred treatment depends on histology and surgical tumor staging using the tumor, nodes, metastasis (TNM) classification system:
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. Mortality in the Mediterranean region and in Asia has been associated with consumption of meat, milk, and animal fat.[16][17] 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.[18] 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.[19] Various food sources of saturated fat have been implicated, including meat, eggs, and whole milk.[20][21][22][23] 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.[24]
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.[25][26]
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.[27] 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.[28] 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.[29] 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.[30]
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.[31][32] Milk consumption also elevates IGF-1 blood concentrations. Some researchers have suggested this is because cow’s milk contains IGF-1 that is identical to the growth factor produced by humans.[33] 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.[34][35]
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 with those with the lowest intakes.[32]
[36]Certain dietary factors have been associated with differences in post-diagnosis survival. Obesity either in early adulthood or 5 years prior to diagnosis is associated with poorer survival in women with obesity.
The Women’s Health Initiative 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.[37]
An observational study of 811 women with invasive ovarian cancer found a survival advantage among those with a higher pre-diagnosis intake of dietary fiber. Decreased survival was found in those who consumed higher glycemic index foods pre-diagnosis. Studies have also suggested a survival advantage for women with ovarian cancer who had consumed more vegetables and less meat prior to diagnosis.[38][39]
Genetic testing, when indicated.
See Basic Diet Orders chapter for guidance on plant-based diets, which may also assist in weight loss, as appropriate.
See also Obesity chapter.
Risk of developing ovarian cancer, or of succumbing to it, may be reduced through healthy diet and lifestyle practices, along with timely screening of those at high risk and early intervention after diagnosis. Family members may support the patient and improve their own health by adopting the same lifestyle changes. Smoking cessation and maintenance of a healthy weight should be encouraged.
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