Special Feature
The Role of Prophylactic Oophorectomy in Women at High Risk of Ovarian Cancer
By David M. Gershenson, MD
Approximately 10% of all epithelial ovarian cancers are hereditary. When the BRCA1 gene was cloned in 1994, lifetime estimates of risk of ovarian cancer for women with BRCA1 germline mutations were as high as 70-80%. Such estimates are now judged to be excessively high based on the fact that early studies were conducted using very high-risk families. Current estimates of lifetime risk of ovarian cancer associated with a BRCA1 germline mutation are approximately 30%. A mutation of the BRCA2 gene, first cloned in 1995, appears to confer a lifetime risk of ovarian cancer in the range of 10%. For women with a family history of ovarian cancer, enrollment in a comprehensive ovarian cancer screening and genetics program should be considered. In such a program, based on family pedigree analysis, women are categorized as either low-risk or high-risk for ovarian cancer. High-risk women are offered genetic testing. However, some may decline testing for myriad reasons, including concern about confidentiality. For high-risk women, with or without genetic testing, there are several alternatives available for risk reduction or screening. If a woman has completed childbearing or is beyond a certain age, prophylactic oophorectomy is an important consideration. Other alternatives include use of oral contraceptives or screening with periodic transvaginal sonography and serum CA 125 testing. Evidence from multiple epidemiologic studies indicates that oral contraceptive use may reduce a woman’s risk of ovarian cancer as much as 50% if taken up to five years. Based on recent data, this protection appears to be equally effective for women with BRCA1 and BRCA2 mutations. Although there is no effective screening method for ovarian cancer for the general population, several centers are focusing on high-risk women. The efficacy of ultrasound and CA 125 testing in this population remains to be defined. There is also some evidence that retinoids may decrease risk of ovarian cancer. More study is required in this area.
For those women who elect prophylactic oophorectomy, the laparoscopic approach is favored. A separate decision is that of whether to combine the procedure with hysterectomy. Although prophylactic oophorectomy seems to be a simple, effective method of ovarian cancer prevention, the facts are not so straightforward. Some women who undergo the procedure will subsequently develop primary peritoneal cancer. This entity was first described by Swerdlow in 1959.1 In a large study of primary peritoneal cancer from M.D. Anderson Cancer Center, we found that the incidence of this entity was approximately 1/10th that of epithelial ovarian cancer.2 Histologically, it is indistinguishable from ovarian cancer with papillary serous features, and the treatment and prognosis are identical to that of advanced ovarian cancer.
In 1982, Tobacman and colleagues reported prophylactic oophorectomy performed in 28 women from 16 families at high risk of ovarian cancer.3 Three (11%) of these women subsequently developed disseminated intra-abdominal malignancy, presumably primary peritoneal cancer. In a later report from the Gilda Radner Familial Ovarian Cancer Registry, Piver and colleges described 324 women from high-risk families who underwent prophylactic oophorectomy.4 Six (1.8%) developed primary peritoneal cancer one, two, five, 13, 15, and 27 years after the operation. In a preliminary report of a multicenter study, Struewing and associates described eight ovarian cancers among 346 non-oophorectomized first-degree relatives of ovarian or breast cancer patients, compared with two cases of peritoneal carcinomatosis among 44 oophorectomized women.5 Compared with the Connecticut Tumor Registry data adjusted for age, race, and birth cohort, there was an approximately 24-fold excess of ovarian cancer among non-oophorectomized women, and a 13-fold excess of primary peritoneal cancer among oophorectomized women. This difference was not statistically significant. Struewing et al stated that a collaborative analysis will be required to determine whether the apparent protective effect of prophylactic oophorectomy is real.
In summary, prophylactic oophorectomy is a good alternative for ovarian cancer prevention in women at high risk for the disease based on family history or genetic susceptibility testing. The true incidence of subsequent primary peritoneal cancer remains unknown, and further study will be necessary to determine it. In the meantime, women contemplating prophylactic oophorectomy should be counseled about available information on primary peritoneal cancer. Regardless of the ultimate data, risk reduction with this procedure appears to be substantial.
References
1. Swerdlow M, et al. Am J Obstet Gynecol 1959;77: 197-200.
2 Fromm GL, et al. Obstet Gynecol 1990;75:89-95.
3. Tobacman JK, et al. Lancet 1982;2:795-797.
4. PiverMS, et al. Cancer 1993;71:2751-2755.
5. Struewing JP, et al. J Nat Cancer Inst Monogr 1995;17:33-35.
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