Risk Reducing Surgery

Approximately 10% of patients with epithelial ovarian cancer carry a deleterious mutation of the BRCA1, BRCA2, or the DNA mismatch repair genes. The presence of these mutations carries a lifetime risk of ovarian cancer ranging from 15% to 54%.73,74 Women who carried these mutations were asked to undergo intensive surveillance or to consider prophylactic salpingo-oophorectomy at age 35 or following the completion of their childbearing. Kauff and associates75 prospectively analyzed 170 BRCA mutation carriers. In the 98 women who underwent prophylactic salpingo-oophorectomy, early-staged tumors were identified in three patients at the time of surgery (3.1%), and primary peritoneal cancer developed in 1 patient during follow-up (1.0%). Of the 72 women who underwent surveillance only, epithelial ovarian or primary peritoneal cancer developed in five (6.9%). The time to breast cancer or BRCA-related gynecologic cancer was also significantly longer in the salpingo-oophorectomy group, with a hazard ratio for subsequent breast cancer or BRCA-related gynecologic cancer of 0.25 (Fig. 7-25). In another multicenter study, Rebbeck and associates76 determined the incidence of ovarian cancer among 259 patients who had undergone prophylactic surgery and compared them with 292 matched controls who had not undergone the risk-reducing procedures. Six patients se

CO o

Salpingo-oophorectomy (n =

CO o

Salpingo-oophorectomy (n =

Months

Number at risk:

Salpingo-oophorectomy 98 69 36 17 11 Surveillance 72 44 28 16 9

Months

Number at risk:

Salpingo-oophorectomy 98 69 36 17 11 Surveillance 72 44 28 16 9

Figure 7-25. Kaplan-Meier estimates of the time to breast cancer or BRCA-related gynecologic cancer among women electing risk-reducing salpingo-oophorectomy and women electing surveillance for ovarian cancer. P = .006 by the log-rank test for the comparison between the actuarial mean times to cancer. (From Kauff ND, Satagopan JM, Robson ME, et al: Risk-reducing salpingo-oophorectomy in women with a BRCA1 or BRCA2 mutation. N Engl J Med 346:1609-1615, 2002, Figure 1.)

were diagnosed with cancer at the time of surgery. After excluding these patients, the authors found that prophylactic surgery reduced the risk of epithelial ovarian cancer by 96%. Finch and associates,77 in the largest multicenter prospective study of patients carrying a deleterious BRCA1 or BRCA2 mutation, evaluated 1273 women with intact ovaries at the inception of the study. Four hundred ninety patients underwent an oophorectomy during the follow-up period; of these, 11 (2.2%) were diagnosed with a malignancy at the time of surgery and a further 7 patients developed primary peritoneal carcinoma following surgery. On the other hand, 32 malignancies were observed among the 783 patients with intact ovaries. The adjusted reduction in risk of malignancy associated with prophylactic oophorectomy was 80%. It is interesting that 3 of the 11 patients diagnosed with an occult malignancy at the time of risk-reducing surgery had a cancer that originated from the fallopian tubes, thus emphasizing the need to remove all of the ovarian tissue and as much of the fallopian tubes as possible. Although some authors have suggested that the intramural portion of the tubes may undergo malignant transformation, there have been no reported cases of such an occurrence.78 The surgery at a minimum should also include a careful survey of all the peritoneal surfaces, a peritoneal cytology, and liberal biopsies of any suspicious area including the omentum to rule out an occult carcinoma. The ovaries and fallopian tubes should be step-sectioned and carefully surveyed for an occult malignancy as well.

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