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Clinical Management of BRCA Mutation Carriers

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Studies on the degree of risk reduction afforded by RRSO have begun to clarify the spectrum of occult cancers discovered at the time of surgery. Primary fallopian tube cancers, primary peritoneal cancers, and occult ovarian cancers have all been reported. Several case series have reported a prevalence of malignant findings among mutation carriers undergoing risk-reducing oophorectomy to be in the range of 2.3% to 33%.[148,149,150,151,152,153,154] The wide variation in prevalence is likely due to differences in surgical technique, pathologic handling of the tissues, and age at RRSO. In addition to occult cancers, premalignant lesions have also been described in fallopian tube tissue removed for prophylaxis. In one series of 12 women with BRCA1 mutations undergoing risk-reducing surgery, 11 had hyperplastic or dysplastic lesions identified in the tubal epithelium. In several of the cases the lesions were multifocal.[155] These pathologic findings are consistent with the identification of germline BRCA1 and BRCA2 mutations in women affected with both tubal and primary peritoneal cancers.[152,156,157,158,159,160,161] One study suggests a causal relationship between early tubal carcinoma, or tubal intraepithelial carcinoma, and subsequent invasive serous carcinoma of the fallopian tube, ovary or peritoneum.[162]

These findings support the inclusion of fallopian tube cancers, which account for less than 1% of all gynecologic cancers in the general population, as a component of hereditary ovarian cancer, and underscore the need for the routine collection of peritoneal washings and careful adherence to comprehensive pathologic evaluation of the entire adnexa using serial sectioning.[163,164] They also raise questions about the optimal surgical approach to provide maximal cancer risk reduction. Some surgeons have recommended hysterectomy in addition to RRSO to remove the remnant of fallopian tube tissue embedded in the uterus, but there is no consensus on this issue, and most, if not all, fallopian tubes cancers appear to arise in the more distal segments of the tube.[152] Several studies have examined whether BRCA1 or BRCA2 mutation carriers are at increased risk of endometrial cancer.[165,166,167,168,169] While case reports and smaller studies suggested an association between BRCA mutations and a specific histology of endometrial cancer called uterine papillary serous cancer,[166] other studies have not found an increased risk of either uterine papillary serous cancer or other histopathologic subtypes of endometrial cancer in BRCA1 or BRCA2 mutation carriers.[167,168] One cohort study of 857 BRCA1 or BRCA2 mutation carriers reported an increased endometrial cancer risk but found that this risk was largely due to tamoxifen use associated with breast cancer treatment.[169] Therefore, in the absence of tamoxifen use or other underlying uterine or cervical problems, hysterectomy is not a necessary component of risk-reducing salpingo-oophorectomy for BRCA carriers.

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WebMD Public Information from the National Cancer Institute

Last Updated: May 16, 2012
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