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    Surgical options for reducing risk in BRCA mutation carriers


    Should RRSO include concomitant hysterectomy?

    Some authors suggest hysterectomy at RRSO to ensure removal of the entire Fallopian tube (Table 2). However, there are no reports of cancers in the uterine cornua of women following RRSO. Removal of the uterus does simplify hormone replacement therapy (HRT) for BRCA mutation carriers by eliminating the need for progestin. Unopposed estrogen can cause uterine cancer and should not be prescribed for a woman with an intact uterus. However, estrogen replacement therapy (ERT), in contrast to combined HRT, has not been associated with breast cancer risk in the general population.22,23 Concomitant hysterectomy and subsequent use of ERT may result in better compliance and less anxiety for a woman than retaining her uterus and using HRT and dealing with the potential for uterine bleeding.

    HRT has been shown to significantly improve many of the menopause-related symptoms that compromise quality of life for younger BRCA mutation carriers following RRSO. Available data suggest that HRT does not increase the risk of breast cancer in BRCA mutation carriers when used for the short term or up to age 50.24,25

    Young BRCA mutation carriers should be encouraged to consider HRT following RRSO because taking estrogen reduces cardiovascular risk after surgically induced menopause and in the early years following spontaneous menopause.26 In BRCA mutation carriers who have had prophylactic mastectomy, residual risk of breast cancer associated with HRT should be minimal.

    The risk of uterine cancer among BRCA mutation carriers is too small to justify routine concomitant hysterectomy at the time of RRSO. One large, prospective study of 4456 BRCA mutation carriers found 17 incident cases of endometrioid uterine adenocarcinoma, which was higher than the 9 cases that would have been expected in the general population.

    Ten of the 17 cases were diagnosed in women who had breast cancer, which is known to increase the risk of uterine cancer regardless of BRCA mutation status. Use of tamoxifen resulted in the highest risk of developing uterine cancer: a 10-year absolute risk of 4.3%, although there are no data regarding uterine cancer risk and length of tamoxifen treatment in BRCA mutation carriers.27 Similar findings have been reported for risk of uterine papillary serous cancers in BRCA mutation carriers, although the precise risk of UPSC is unknown.28,29

    The additional cost and surgical morbidity of concomitant hysterectomy at the time of RRSO must be balanced with the BRCA mutation carrier’s goals and preferences regarding risk reduction. Overall surgical morbidity approximately doubles with the addition of concomitant hysterectomy and may necessitate a laparotomy.30,31

    For women with existing gynecologic pathology such as symptomatic fibroids, history of cervical dysplasia, or adenomyosis, concomitant hysterectomy at the time of RRSO is reasonable. BRCA mutation carriers who have taken or plan to take tamoxifen should also be counseled to consider concomitant hysterectomy. Further study of the incidence of endometrial or cervical pathology in women who keep their uterus after RRSO is necessary to better inform clinical care recommendations.

    Ilana Cass, MD
    Dr. Cass is an Assistant Professor of Obstetrics and Gynecology, UCLA/Cedars-Sinai Medical Center, Los Angeles, Calif.


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