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Certain Measures May Help Prevent Ovarian Cancer in High-Risk Women


 

SAN FRANCISCO — Physicians play an important role in identifying women at high risk for ovarian cancer because when such a woman is identified, much can be done to prevent the cancer, Karen H. Lu, M.D., said at the annual meeting of the American College of Obstetricians and Gynecologists.

The lifetime risk of ovarian cancer in the general population is about 1.7%, and most cases are found in a late stage. But among women who have certain mutations in the BRCA1 or BRCA2 genes, the lifetime risk rises to 40%–50%. These genes also are responsible for hereditary forms of breast cancer.

Only about 10% of ovarian cancers can be attributed to these mutations, with the remaining 90% regarded as “sporadic.” While one marker of ovarian cancer—the antigen CA-125—has been found, screening the public at large has not been recommended, since the poor specificity of the CA-125 test, combined with the cancer's low prevalence, would result in a high rate of false positives.

But for women at high risk, screening, chemoprevention, and preventive surgery may make more sense, said Dr. Lu of the University of Texas M.D. Anderson Cancer Center, Houston. The trick is to determine which women are at high risk.

The strongest indication of risk is a family history of breast or ovarian cancer. Your index of suspicion should rise whenever a woman mentions several relatives who have died young from these cancers, Dr. Lu recommended.

Ethnic heritage can be another indicator. Among Ashkenazi Jewish women with ovarian cancer, 40%–50% have BRCA1 or BRCA2 mutations. The general population of Ashkenazi Jewish women has a 2%–3% chance of carrying one of the mutations, compared with 1 in 500 for the full U.S. population.

When a woman reports a strong family history of cancer, genetic testing is worthwhile, Dr. Lu said. If possible, the testing should start with a family member with a confirmed case of ovarian cancer. The test is a simple blood draw with no fasting required. But the testing, which involves full sequencing of both BRCA1 and BRCA2, costs about $3,000. Many insurance carriers are willing to pick up the tab.

If a mutation is identified in the patient with cancer, other family members need not have the full sequencing done. Instead, they need a simpler test that would confirm or refute the presence of that specific mutation. This test costs about $350. If the mutation is not present, a physician can be confident that the woman's risk of ovarian cancer is 1.7%, no higher than the general population.

Women at high risk may benefit from CA-125 screening, although a definitive recommendation won't be available until the large Risk of Ovarian Cancer Algorithm (ROCA) study is completed. It is known that absolute CA-125 levels are not as important as whether a woman's level remains constant or increases. In the ROCA study, blood levels of CA-125 are being measured every 3 months. An increasing CA-125 level appears to carry a high risk of ovarian cancer.

Dr. Lu recommended women at high risk consider chemoprevention. Oral contraceptives are known to reduce the risk of ovarian cancer by about 50%. There's a detectable effect after 1 year of use, and the protection increases for each additional year of use.

The definitive preventive technique is risk-reducing salpingo-oophorectomy (RRSO). Dr. Lu recommended that women past childbearing who are known mutation carriers and over age 35 years should undergo the surgery. “As a secondary benefit, removing their ovaries reduces their breast-cancer risk by 50%.”

When performing an RRSO, it's important to enlist the aid of the pathologist. About 8%–17% of patients will have occult, microscopic cancers at the time of prophylactic surgery, a relatively high rate. Unless serial sectioning (every 2 mm) is specifically requested, the pathologist is likely to take only a single “representative” sample of the ovary and the fallopian tube.

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