Ovarian Cancer: Rates, Risk Factors,
Prevention and Screening

Introduction

Ovarian cancer is the fourth leading cause of cancer deaths in American women today. About one in seventy women will be diagnosed with this cancer in their lifetime. The death rate (see table) from ovarian cancer is high, due in part to the fact that most women have advanced disease that has spread outside the ovaries at the time of diagnosis.

Signs and Symptoms

Most women do not have recognizable symptoms when the disease is in its early stages. Even when the disease has spread, symptoms may be vague and not specific to ovarian cancer. Symptoms of ovarian cancer can include:

Abdominal fullness or bloating
Pelvic heaviness or pressure
Pain with intercourse
Vaginal bleeding or discharge
Gastrointestinal symptoms such as lack of appetite, nausea, vomiting or constipation.

Risk Factors

The exact cause of most ovarian cancer is not known. There is a general relationship between the number of times that a woman ovulates in her lifetime and the risk of ovarian cancer. This may be because the process of ovulation causes injury to the epithelial surface of the ovary. Over time, repeated injury and repair may lead to cancer. Several factors may alter the number of lifetime ovulations and subsequently protect against ovarian cancer. These include: late age of menarche, early onset of menopause, pregnancy, prolonged breast feeding (1+ years), and use of oral contraceptives (taken for 5+ years). The risk of ovarian cancer associated with the use of fertility drugs to stimulate ovulation is controversial and currently being studied.

Some women who develop ovarian cancer have a strong family history of cancer, particularly breast and ovarian cancer. Of all ovarian cancer cases, 5-10% are felt to be clearly associated with a familial predisposition. There are several inherited genetic mutations that have been associated with an increased risk of ovarian cancer: BRCA1, BRCA2 and any of the genes associated with hereditary non-polyposis colorectal cancer (HNPCC). Of these, BRCA1 is associated with the highest increase in the risk of ovarian cancer.

Men, as well as women, may carry genetic mutations that can be passed on to their children. Therefore, it is important to examine the cancer history of both the mother’s and father’s families when assessing an individual’s risk for ovarian cancer.

Primary Prevention

Women at increased risk for ovarian cancer can take certain steps to reduce this risk. These include the use of oral contraceptives or prophylactic surgical removal of the ovaries (prophylactic oophrectomy). As a preventive measure, prophylactic oophrectomy is controversial. Most authorities in the field believe that this will reduce the risk of ovarian cancer, but it is not clear by how much. This is because the risk of primary peritoneal cancer is also increased in women with an inherited ovarian cancer predisposition. Primary peritoneal cancer arises from cells on the surface of the abdomen and pelvis and is almost indistinguishable from ovarian cancer. Even after removal of the ovaries, a woman may still be at risk for peritoneal cancer. Furthermore, removal of the ovaries will cause menopause.If the ovaries are removed at an early age, premature menopause may cause hot flashes and significant health risks including heart disease and osteoporosis. Since many women at risk for ovarian cancer are also at risk for breast cancer, these women are usually counseled against the use of hormone replacement therapy.

Screening Strategies

There are currently no proven effective methods for the early detection of ovarian cancer. A large trial is currently underway to test the effectiveness of the CA125 blood test and ultrasound. The CA125 blood test is elevated in about 80% of women with advanced ovarian cancer, but is abnormal in less than half of women who have disease that is confined to the ovary and has not yet spread. Thus, the CA125 test will miss more than half of the cases of early disease. In addition, there are a large number of non-cancerous causes of an elevated CA125 including common conditions such as endometriosis, benign fibroid tumors of the uterus, pelvic inflammatory disease (PID), and even certain phases of the menstrual cycle. It is estimated that if every woman with an elevated CA125 underwent surgery, there would be about 50 unnecessary surgeries for every case of ovarian cancer detected.

Screening with transvaginal ultrasound, color Doppler imaging of the ovaries, and pelvic examination depend on the presence of a mass in the ovary with characteristics that allow the examiner to differentiate between benign and cancerous lesions. Unfortunately, benign masses and common cysts of the ovary are often difficult to distinguish from malignant tumors.

Conclusion

Perhaps the biggest obstacle to effective screening, early detection, and (ultimately) the prevention of ovarian cancer, is our lack of understanding of exactly how and why this disease develops. For the time being, women who are concerned about their ovarian cancer risk should be sure to have regular gynecologic checks and maintain an open and ongoing dialogue with their health care providers about appropriate ways to address their health concerns.

Deborah Armstrong, M.D.>