Prophylactic Surgery

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To date, prophylactic oophorectomy has been the most definitive method for preventing ovarian cancer in high-risk women, and recent evidence shows that the procedure might also decrease the risk of breast cancer. In 2002, Rebbeck et al. (181) examined 551 women with germline mutations in BRCA1 and BRCA2, of which 259 had and 292 matched controls had not undergone prophylactic oophorectomy. Among the women undergoing surgery, six (2.3%) were diagnosed with occult stage I ovarian cancer at the time of surgery, and 2 women (0.8%) were later diagnosed with primary peritoneal cancer. In contrast, 58 women (19.9%) out of the women in the control group were diagnosed with ovarian cancer after a mean follow-up of 8.8 years. Excluding the 6 diagnosed with occult cancer, prophylactic oophorectomy significantly decreased the risk of ovarian or primary peritoneal cancer by 96%. In addition, 99 women were studied for the risk of developing breast cancer; 21 women (21.2%) developed breast cancer from among the women undergoing prophylactic surgery, compared with 60 (42.3%) controls, showing a 53% reduction in risk. A similar study by Kauff et al. (182) prospectively followed 170 women, age 35 or older, with either BRCA1 or BRCA2 mutations. Among the 98 women who chose prophylactic oophorectomy, breast cancer was diagnosed in 3 (3%) and primary peritoneal cancer was diagnosed in 1 (1%) at a mean follow-up of 24.2 months. In contrast, of the 72 women who chose surveillance, breast cancer was diagnosed in 8 (11%), and ovarian or primary peritoneal cancer was diagnosed in 5 (7%). Prophylactic oophorectomy decreased the risk of subsequent ovarian/primary peritoneal cancer by 85%, and the risk of breast cancer by 70%.

Prophylactic oophorectomy may be performed laparoscopically on an outpatient basis in the vast majority of women, with low morbidity and mortality. However, aside from perioperative risks and issues associated with early menopause, patients should be carefully counseled that the procedure might not be entirely protective. Because primary peritoneal cancer has been reported to occur in 0.8-11% of high-risk women even after prophylactic oophorectomy (67,181-183) thorough exploration of the pelvic and abdominal cavity should be performed at the time of surgery. Also, complete meticulous histological assessment of the ovaries should be performed, in order to exclude the presence of occult malignancy, which has been reported to occur in 2-4% of women undergoing prophylactic oophorectomy (181,184-186). Given the documented increased risk of fallopian tube carcinoma in women with BRCA1 and BRCA2 mutations, the surgeon should take care to remove the entire fallopian tube. Without performing hysterectomy or corneal resection, a small interstitial portion of fallopian tube will always be retained, although this is felt to contribute negligible risk given that no cases of fallopian tube carcinoma after prophylactic salpingo-oophorectomy have been reported.

As no consistent data exist to support the relationship of BRCA1 and BRCA2 mutations to endometrial cancer, current recommendations for surgical prophylaxis do not include routine hysterectomy. However, women undergoing tamoxifen therapy for a previous diagnosis of breast cancer might be considered candidates for hysterectomy. Given that women with breast cancer may be treated for five years, and that tamoxifen has been well documented to increase the risk of endometrial cancer (187,188) as well as cause subendothelial thickening, abnormal uterine bleeding, and endometrial polyps, these women may consider hysterectomy at the time of prophylactic salpingo-oophorectomy after careful consultation with their physician. Women with HNPCC should be offered both prophylactic oophorectomy and hysterectomy to decrease the risk of future gynecological malignancy.

Compared with intensive surveillance, prophylactic oophorectomy appears to be preferred by women at high-risk for ovarian cancer (152,189,190). Tiller et al. (190) noted a high level of satisfaction among women undergoing the procedure, accompanied by decreased levels of anxiety. Given the lack of clearly effective surveillance regimens, as well as the usually manageable side effects of early menopause, the clear reduction in ovarian cancer risk provided by surgical extirpation provides a strong argument for prophylactic oophorectomy in high-risk women.

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