Over the past few years, knowledge of genetic susceptibility to breast and ovarian cancer has increased substantially.  Testing for mutations in the BRCA1 and BRCA2 genes is becoming increasingly available to women who are believed to have an elevated risk of familial predisposition to breast or ovarian cancer. At the same time, more patients are turning to gynecologists, gynecologic oncologists, and other health care providers for estimates of their own and their daughters’ risks of developing ovarian cancer and for information about options for surveillance and prevention.

In discussions of these issues,  patients must be provided with information on a well-researched pedigree of the family; risks associated with use of oral contraceptives and hormone replacement therapy; risks of prophylactic oophorectomy; and the possibility that peritoneal carcinoma may develop subsequent to prophylactic oophorectomy.

Indications
Some authors suggest a prophylactic bilateral oophorectomy in patients undergoing hysterectomy or other pelvic surgery to reduce the patient’s risk of developing ovarian cancer in the future.

This potential benefit, however, has to be balanced against the long-term risks of estrogen withdrawal, including a possible increased risk of cardiovascular disease and predisposition to osteoporosis. These potential risks are particularly important in patients with breast cancer, in whom exogenous estrogens are usually contraindicated.

Prophylactic oophorectomy is also sometimes considered in women with familial cancer risk. Approximately 10% of ovarian cancers are believed to be familial, and 90% of these hereditary ovarian cancers can be accounted for by mutations in BRCA1 or BRCA2.

Patients with 1 first-degree relative with ovarian cancer have an approximately 5%  risk,  and patients with 2 first-degree relatives with ovarian cancer have a 7% risk. This risk is considerably higher if a woman tests positive for BRCA1 or BRCA2 mutations-the lifetime risk of ovarian cancer in women who are known to have mutations in BRCA1 or BRCA2 is 15-60%. It is important to counsel such mutation carriers that oophorectomy not only dramatically reduces ovarian cancer risk but also confers a 50% reduction in the incidence of breast cancer in this select group of patients.  Women with premenopausal breast cancer who have tested negative for BRCA1 and BRCA2 mutations have a lifetime risk of ovarian cancer of 3-5%. Recent studies have demonstrated that women from so-called breast cancer families without BRCA1 and BRCA2 mutations are most likely not at increased risk for ovarian cancer.

Hereditary ovarian cancers tend to present at an earlier age,  but the optimum age at which to perform prophylactic oophorectomy remains unknown.  The Gilda Radner Familial Ovarian Cancer Registry recommends oophorectomy when fertility is no longer important to the woman or by the age of 35 years. In the Gynecologic Oncology Center, we recommend that prophylactic oophorectomy be performed 5-10 years earlier than the age when cancer developed in the closest affected relative or by 40 years of age if the patient has finished childbearing.

Patient Counseling and Treatment Selection
The surgical approach to oophorectomy must be discussed carefully with the patient. Laparoscopic oophorectomy is the preferred treatment method in the absence of contraindications such as multiple prior abdominal surgeries, morbid obesity, history of severe endometriosis, pelvic inflammatory disease, or tubo-ovarian abscesses. Laparoscopic oophorectomy has several advantages:  the procedure can be performed on an outpatient basis; there is minimal blood loss and decreased need for postoperative analgesia; and the patient can return more quickly to normal daily activities. In experienced hands, if an unexpected ovarian cancer is encountered, laparoscopic staging can be performed safely.

The disadvantages and benefits associated with performing a hysterectomy at the time of the oophorectomy also need to be addressed. The disadvantages include an increase in overall morbidity due to increased duration of the surgical procedure and increased blood loss. The cost of the procedure is also higher when hysterectomy is performed at the same time as oophorectomy. On the other hand, BRCA1 and BRCA2 mutations may be associated with increased risk of fallopian tube carcinoma, and complete excision of the fallopian tubes requires hysterectomy.

KEY   PRACTICE   POINTS

•   Women undergoing standard or high-dose chemotherapy are at increased risk for vulvar and vaginal infections.
•   Any abnormal vaginal bleeding in a patient with breast cancer should be fully evaluated to rule out endometrial carcinoma.
•   Urinary incontinence and prolapse occur most commonly in menopausal women or after traumatic vaginal birth. Urinary incontinence may also be an early symptom of an undiagnosed pelvic mass.
•   Patients receiving tamoxifen or other hormonal agents should be monitored for the development of endometrial carcinoma with yearly physical examinations. An endometrial biopsy must be performed if abnormal bleeding has occurred.
•   Vaginal sonography and hysteroscopy are very useful diagnostic tools in patients who have vaginal bleeding or other pelvic symptoms.
•   Prophylactic oophorectomy may be warranted in certain patients who are genetically predisposed to the development of ovarian cancer.

Patients should be informed that peritoneal carcinoma develops in 1.8-10.7% of patients after oophorectomy.

Many patients choose not to undergo surgical excision of the ovaries and choose close observation instead. With these patients, it is important to discuss the limitations of the other preventive measures available to decrease the chances of developing ovarian cancer. It is not known whether any of these preventive measures provide the same benefit to carriers of BRCA1 and BRCA2 mutations as they do for the general population.

Oral contraceptives have been shown to reduce the risk of ovarian cancer development by 50%, and the protective effect persists for 10-15 years after the oral contraceptive has been stopped. Data are unclear regarding the impact of oral contraceptives on ovarian cancer risk in BRCA1 and BRCA2 mutation carriers-two large studies reached opposite conclusions (Narod et al., 1998; Modan et al., 2001). In addition, there is evidence that use of oral contraceptives may increase the risk of breast cancer. At this time,  oral contraceptives cannot be recommended for patients who have been diagnosed with breast cancer.

Surveillance and screening for ovarian cancer need to be addressed, particularly for known carriers of BRCA1 or BRCA2 mutations. The best available tools for early detection of ovarian cancer are physical examination combined with determination of the serum CA-125 level and transvaginal sonography; however, these methods remain only marginally effective as screening approaches.  Both CA-125 and transvaginal sonography have a very high false-positive rate, particularly in premenopausal women. Even in patients with known first- or second-degree relatives with a history of ovarian cancer,  Bourne et al.  (1993)  found that ten surgical explorations were required to identify one patient with ovarian cancer. An even higher number of unnecessary procedures would have to be performed in patients whose only risk factor was a personal history of breast cancer.

While we await tests with higher sensitivity and specificity, patients at risk are offered twice-annual physical examination, a rectovaginal examination combined with serum CA-125 determination, and transvaginal sonography.  More attention is being focused on the psychological impact of increased susceptibility for ovarian cancer. Recent studies have highlighted the importance of providing personalized feedback and counseling interventions tailored to the individual’s psychological profile. Trained genetic counselors are key providers in the care of this patient population.

Elizabeth R. Keeler, Pedro T. Ramirez, and Ralph S. Freedman
Committee on Gynecological Practice, the American College of Obstetricians and Gynecologists. Obstet Gynecol 2007

References