Ovarian cancer: Identifying and managing high-risk patients
Two cases illustrate when to refer for genetic counseling and what to advise women concerned about prevention.
The 3-2-1 rule for genetic counseling
Genetic counseling is indicated when the patient meets the “3-2-1” rule, known as the modified Amsterdam criteria:
- 3 affected individuals with either colorectal or ovarian cancer, in
- 2 successive generations, with at least
- 1 who developed cancer under the age of 50 years.
When HNPCC is present
Women with documented HNPCC have a 70% lifetime risk of developing endometrial cancer and a lifetime risk of ovarian cancer of 11% or more. Testing for mutation in mismatch repair genes can be performed on peripheral leukocytes. Alternatively, the primary tumor from affected individuals can be assessed for the presence of microsatellite instability, a consequence of defective mismatch repair.3
How to obtain a family history
Women with a significant family history of breast, colorectal, endometrial, or ovarian cancer may face an elevated risk of ovarian cancer. Basic questions about the occurrence of these malignancies in first-degree (mother, sister, daughter) or second-degree (aunt, grandmother) relatives must be a component of every gynecologic history.
1-question assessment
The following question is a simple but effective way to assess familial cancer risk: “Has anyone in your family had breast cancer under the age of 35, or colorectal, uterine, or ovarian cancer?” If so, ask further questions about the relative’s age at onset and how the affected person is related to the patient.
Although an informal pedigree can be constructed in a few moments, a formal pedigree is a more daunting task. More than half of family histories of ovarian cancer are inaccurate—and the error rate increases if the affected family member is a distant relative.8
Moreover, not all ovarian cancers are associated with genetic syndromes. Serous epithelial ovarian, fallopian tube, and peritoneal cancers dominate in BRCA-associated syndromes, whereas mucinous epithelial cancers are very rare. Germ-cell and stromal neoplasms as well as epithelial tumors of low malignant potential are excluded when assessing genetic risk.
Additional documentation is often necessary to verify the history. Such medical detective work may be beyond what a generalist is willing to perform. In that case, referral to a genetic counselor is the next step.
When to refer
Recommendation. If she is of Ashkenazi Jewish descent, like the patient described at the beginning of this article, only 1 first-degree relative indicates referral for genetic counseling.
If the patient claims at least 2 first-degree or second-degree relatives with breast cancer under the age of 35, or with ovarian cancer, suspect a genetic syndrome.
Family histories of particular concern include breast and ovarian cancer in a single individual, or any case of male breast cancer. Refer these patients to genetic counseling for formal pedigree analysis and possible testing for genetic predisposition. In the case of HNPCC, refer the patient if the modified Amsterdam criteria are met.
What does a genetic counselor do?
One of the most important roles of a genetic counselor is constructing as accurate a pedigree as possible. In some cases, this requires much effort on the part of both patient and counselor. It is not uncommon for the counselor to request outside pathology reports, operative notes, and death certificates to verify cancer cases. Pathology slides also may be necessary, while tissue blocks occasionally are requested to assist in genetic testing.
When testing is warranted
Genetic predisposition testing should be undertaken only after formal consultation with a genetic counselor who has expertise in cancer predisposition syndromes. As a policy statement from the American Society of Clinical Oncology concludes, genetic testing for cancer susceptibility should be performed only when:
Obesity is associated with increased risk of ovarian cancer mortality.
- pre- and post-test counseling is available,
- the test can be interpreted, and
- the results will help in medical and surgical management.
CASE 2
A 65-year-old obese nullipara is currently on year 10 of combined hormone replacement therapy (HRT). Although she has no family history of breast or ovarian cancer, she asks about her risk of developing ovarian cancer.
Other risk factors
Findings on the following potential risk factors for ovarian cancer may help address this patient’s concerns:
Dietary factors
In a recent study, obesity was associated with an increased risk of ovarian cancer mortality.10 Women who eat a diet high in saturated fat and low in vegetable fiber also may face an increased risk.
