The value of prophylactic salpingo-oophorectomy in these patients is documented (77–83). Women at high risk for ovarian cancer who undergo prophylactic salpingo-oophorectomy have a risk of harboring occult neoplasia: in one series of 98 such operations, 3 (3.1%) patients had a low-stage ovarian malignancy (80). The protection against ovarian cancer is excellent: the performance of a prophylactic salpingo-oophorectomy reduced the risk of BRCA-related gynecologic cancer by 96% (80). In a series of 42 such operations, 4 patients (9.5%) had a malignancy, 1 of which was noted at surgery and 3 that were microscopic; all were smaller than 5 mm (78). Although the risk of ovarian cancer is significantly diminished, there remains the small risk of peritoneal carcinoma, a tumor for which women who have mutations in BRCA1 and BRCA2 may have a higher predisposition. In these series, the subsequent development of peritoneal carcinoma was 0.8% and 1%, respectively (78,79). The risk of developing subsequent breast cancer was reduced by 50% to 80%.
The role of hysterectomy is more controversial. Most studies show no increase in the rate of uterine and cervical tumors, but there are rare reports of an increase of papillary serous tumors of the endometrium (83). Women on tamoxifen are at higher risk for benign endometrial lesions (e.g., polyps) and endometrial cancer. It is reasonable to consider the performance of a prophylactic hysterectomy in conjunction with salpingo-oophorectomy, but this decision should be individualized.
The survival of women who have a BRCA1 or BRCA2 mutation and develop ovarian cancer is longer than that for those who do not have a mutation. In one study, the median survival for mutation carriers was 53.4 months compared with 37.8 months for those with sporadic ovarian cancer from the same institution (84).
Current recommendations for management of women at high risk for ovarian cancer are summarized as follows (72,82): 1.
Women who appear to be at high risk for ovarian or breast cancer should undergo genetic counseling and, if the risk appears to be substantial (i.e., a calculated risk of at least 10% in having a mutation in BRCA1 or BRCA2), may be offered genetic testing for BRCA1 and BRCA2.
2.
Women who wish to preserve their reproductive capacity can undergo screening by transvaginal ultrasonography every 6 months, although the efficacy of this approach is not established.
3.
Oral contraceptives should be recommended to young women before they embark on an attempt to have a family.
4.
Women who do not wish to maintain their fertility or who have completed their families should be recommended to undergo prophylactic bilateral salpingooophorectomy after the age of 35, but by age 40 years. The risk of ovarian cancers under the age of 40 is very low but the decision regarding the age of surgery should be based on the age of onset of ovarian cancers in the family. Most BRCA2-related ovarian cancers tend to occur after the age of 50, whereas BRCA1-related cancers occur at an earlier age. The risk should be clearly documented, preferably established by BRCA1 and BRCA2 testing, before salpingo-oophorectomy is performed. These women should be counseled that this operation does not offer absolute protection, because peritoneal carcinomas can occur after bilateral salpingo-oophorectomy (25,28,83).
5.
In women who have a strong family history of breast or ovarian cancer, annual breast screening should be performed beginning at age 30 years using a combination of magnetic resonance imaging (MRI), mammograms, and ultrasound. Ideally, these women should be followed in clinics that manage women at high risk for cancer.
6.