Epidemiological and Genetic Factors Associated With Ovarian Cancer

Monica R. McLemore, RN, MPH; Christine Miaskowski, RN, PhD, FAAN; Bradley E. Aouizerat, PhD, MAS; Lee-may Chen, MD; Marylin J. Dodd, RN, PhD, FAAN

Disclosures

Cancer Nurs. 2009;32(4):281-288. 

In This Article

Current Screening and Early Detection of Ovarian Cancer

Screening

There is inadequate evidence to support screening for ovarian cancer in the general population. However, 2 large, ongoing, prospective, randomized controlled trials (RCTs)[2,3] should provide important information about the efficacy of using transvaginal ultrasound (TVU), CA-125, and screening examinations for the early detection of ovarian cancer.

The first RCT, being conducted in the United States, is the Prostate, Lung, Colorectal, and Ovarian screening trial, sponsored by the National Cancer Institute. This study includes 37,000 healthy postmenopausal women between 55 and 74 years of age who were randomized to either an annual CA-125, TVU, and pelvic examination or standard care.[2] The end points are cost and the establishment of important time points for screening. The outcome variable is mortality. Patients will be followed up for 13 years. Based on preliminary analyses, 1,338 participants (4.7%) had abnormal TVU, and 402 participants (1.4%) had abnormal CA-125 (only 34 had abnormal results on both tests).[3] Data from this RCT pertaining to the efficacy of screening are still being analyzed.

The second study, being conducted in the United Kingdom, has enrolled 200,000 postmenopausal women and is called the North Thames Ovarian Cancer Study. This study is attempting to determine the sensitivity of CA-125 plus TVU versus TVU alone as screening measures for ovarian cancer. Study end points include quality of life, morbidity, and cost.[3,4] Enrollment was completed in 2005, and results should be forthcoming soon. These studies should provide valuable information about the crucial time points and the optimal screening methods for ovarian cancer.

Early Detection

Early detection of ovarian cancer has been a goal of clinical research. However, the underlying biology of the disease and its vague symptom profile have rendered it difficult to diagnose at early stages. A recent consensus statement[5] jointly issued by the Gynecologic Cancer Foundation,[5] Society of Gynecology Oncologists, and the American Cancer Society identified 4 symptoms that are more likely to occur in women with ovarian cancer: (1) bloating, (2) pelvic or abdominal pain, (3) difficulty eating or feeling full quickly, and (4) urinary symptoms (ie, urgency or frequency). Taken together, these symptoms are called the Ovarian Cancer Symptom Index (OCSI). The release of this statement was not without controversy; the symptoms identified are common in healthy women, and the survey used to identify the symptoms included in the index was not prospectively validated in a sample of healthy women.[6]

Two studies have provided evidence to support the clinical use of the OCSI.[7,8] Goff and colleagues[7] used a 23-item symptom survey to develop the OCSI. Using this survey, the symptoms were collapsed into a single variable if the correlation coefficient among the symptoms was 0.70 or greater.[7] Odds ratios (ORs) were used to compare symptoms of different duration, frequency, and severity. Finally, logistic regression was used to determine the independent contribution of the symptoms to predict risk for ovarian cancer in a different sample of high-risk women.[7]

The OCSI was considered positive if women reported any of the following 6 symptoms more than 12 times in 1 month but that they were not present for more than 1 year: pelvic/abdominal pain, increased abdominal size/bloating, and feeling full/difficulty eating. Once the symptom index was developed, the study cohort was divided into an exploratory group and a confirmatory group to test the sensitivity and specificity of the index in the confirmatory sample. The index had a sensitivity of 56.7 to detect early-stage and 79.5 to detect advanced-stage ovarian cancer. The specificity of the index was 90% in women older than 50 years and 86.7% in women younger than 50 years of age.

The second study,[8] from the same research group, combined data from the symptom index with CA-125 values to determine if it improved the sensitivity and specificity of the index. This prospective case-control study enrolled 254 healthy high-risk women (due to family history) and 75 women with ovarian cancer. Cases were defined as women scheduled for surgery for evaluation of a mass suggestive of tumor. Using methods from their previous study,[7] the investigators found that cases were more likely to be older and have elevated levels of CA-125 and a positive OCSI score. Fifty-three percent of the cases had a positive symptom index score and an elevated CA-125; 25.3% had only an elevated CA-125; and 50% of the total group of cases and controls had a positive symptom score (which represented 10.7% of the total case group). Symptom index scores independently predicted an ovarian cancer diagnosis after adjusting for CA-125 levels (ie, OR, 11.51; 95% confidence interval [CI], 4.62-28.66). However, when used alone, the symptom index score had a lower sensitivity than CA-125 level (64% vs 78.7%). These findings suggest that the combination of CA-125 and the OCSI score improved the sensitivity of detecting ovarian cancer in women participating in a high-risk screening program.

Prevention

Two methods of primary prevention of ovarian cancer are available for high-risk populations, namely, chemoprevention and risk-reducing salpingo-oophorectomy (RRSO).[9,10,11,12,13,14] Chemoprevention of ovarian cancer has not been studied independently. However, several studies designed to evaluate other outcomes have noted a decreased risk for ovarian cancer in patients taking oral contraceptives (OCPs).[9,12,13,14,15,16,17]

In a large review of 12 case-control studies in the United States,[18] OCP use and ovarian cancer risk had an overall OR of 0.67 (95% CI, 0.37-1.2), an OR of 0.62 (95% CI, 0.24-1.6) in African-American women, and an OR of 0.70 (95% CI, 0.52-0.94) in white women.[19] These data suggest that ever-users of OCPs had a decreased risk for ovarian cancer.[18] The benefit of OCP use remained in women who had used OCPs for 2 to 5 years and leveled off in women who used them for 6 years or longer. These data suggest that 5 years of OCP use confers a 50% decrease in the risk for ovarian cancer with a protective effect that remains for up to 10 years after OCP use is discontinued.[9,18,20] The mechanism by which OCP use protects against the development of ovarian cancer is its progestin effect (ie, decrease in the number of ovulatory events).[13,20]

Risk-reducing salpingo-oophorectomy is defined as the removal of ovaries in women with no documented ovarian disease or with a known increased risk for ovarian cancer.[13] Four studies[9,10,11,12] evaluated the use of RRSO in women who were at high-risk for ovarian cancer. Across these studies, RRSO decreased the risk for ovarian cancer by more than 90% and for breast cancer by approximately 50%, with a mean follow-uptime of 5 years. While surveillance of high-risk women was evaluated, surgery was considered superior for risk reduction.[11,12] Patients tended to report higher satisfaction with surgery and little anxiety or regret.[13,21] Longer-term follow-up is still needed. Microscopic occult disease has been found in 10% to 15% of women with genetic predisposition for ovarian cancer, and even with negative pathology, these women are still at increased risk for primary peritoneal carcinoma.[13]

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