Surveillance of survivors: Follow-up after risk-reducing salpingo-oophorectomy in BRCA 1/2 mutation carriers
Research highlights
► We examine medical surveillance after risk-reducing salpingo-oophorectomy in BRCA1/2 mutation carriers. ► Testing and surveillance for bone loss, menopause, and peritoneal cancer is inconsistent. ► Optimizing survivorship after RRSO requires standardized national guidelines.
Introduction
In 1994 deleterious mutations in the BRCA1 and BRCA2 genes were reported to be the cause of an inherited susceptibility to breast and ovarian cancers [1], [2]. Shortly thereafter, risk-reducing salpingo-oophorectomy (RRSO) was shown to decrease lifetime ovarian cancer risk by up to 90% [3] and breast cancer risk by 50% in carriers of BRCA1 and BRCA2 (BRCA 1/2) mutations [3]. These discoveries brought new hope to the goal of cancer prevention.
While considered the most aggressive modality to reduce ovarian cancer risk, surgery is more efficacious than either intensive screening or chemoprevention [4], [5]. It has also been shown that undergoing RRSO at a younger age confers increased survival benefit [4]. As such, experts currently recommend RRSO in BRCA1/2 mutation carriers at the completion of childbearing, between the ages of 35 and 40, or younger in carriers with a familial cancer history of early onset [6].
The identification of those at risk for hereditary ovarian cancer, coupled with the standard practice of surgical intervention by the age of 40, has increased the cohort of long term survivors. However, long term survivorship comes at a cost. These women will experience premature surgical menopause and are susceptible to heart disease [7], metabolic syndrome [8] and osteoporosis [9] ten to fifteen years earlier than those who undergo natural menopause.
In addition to the risks of surgical menopause, BRCA1/2 mutation carriers continue to have post-RRSO cancer risk. They are at an estimated 3–4% lifetime risk for the development of primary peritoneal cancer (PPC) [10], [11], [12] and require continued post-operative surveillance.
Recent evidence suggests that the population of BRCA1/2 mutation carrier women exposed to premature surgical menopause is increasing. As of 2010, 51% of patients in our Cancer Risk Program at UCSF underwent RRSO [13] — this is consistent with other reports of RRSO uptake [14], [15].
Current practice guidelines for post-operative monitoring and treatment of surgical menopause and surveillance of PPC and bone density after RRSO are vague. The Society of Gynecologic Oncology (SGO) 2005 committee statement notes the paucity of evidence upon which to make recommendations; “limited information is available regarding management of women following risk-reducing salpingo-oophorectomy” [15]. The National Cancer Care Network (NCCN) 2010 practice guideline is similarly equivocal; “counseling (re: RRSO) includes a discussion of … management of menopausal symptoms, possible short term HRT and related medical issues” [6].
Treatment of menopause has been fraught with controversy in the past 10 years. The Women's Health Study led many clinicians to avoid the use of HRT in women undergoing natural menopause [16]. In BRCA1/2 mutation carriers the evidence suggesting increased breast cancer risk with the use of HRT [17] has led to concern that HRT use in women undergoing RRSO will negate the breast cancer risk reduction conferred by RRSO. Although, more recent studies have suggested that short term HRT post-RRSO is not associated with increased breast cancer risk [18], [19], given the limitations of nonrandomized studies [20], [21], HRT's safety as a treatment for menopause remains a subject of debate.
Diagnosis of hereditary cancer risk and early intervention to prevent cancer development has resulted in a new cohort of cancer survivors. The goal of this study is to characterize the post-surgical menopause symptom and sequelae surveillance and treatment BRCA1/2 mutation carriers receive with respect to PPC, bone loss and menopausal symptoms. These three conditions are routinely addressed in our follow-up visits in the gynecologic oncology clinic and are potentially vital to the promotion of long term survival.
Section snippets
Methods
The University of California San Francisco (UCSF) provides genetic counseling and testing to families with a high risk of familial cancers through the Cancer Risk Program (CRP). Characteristics of this population have been described by Lee et al. [22]. During intake visits, patients are offered participation in an IRB approved 20-year follow-up research protocol. Approximately 97% of patients sign informed consent. Using published guidelines [6], [23], we advise women who test positive for a
Results
Of the 51 responders, there were 32 (63%) BRCA1 mutation carriers and 19 (37%) BRCA2 mutation carriers. Median age at RRSO was 46 (range 31–68). Questionnaires were administered at a median of 6 years after surgery (range 1–10). In 14 cases, the RRSO procedure also included hysterectomy. At the time of questionnaire administration 24 respondents (47%) were younger than age 50. Thirty-three (64%) subjects had a history of breast cancer prior to RRSO. An additional four (7.8%) patients were
Discussion
This study describes the current surveillance practice in our cohort of BRCA1/2 mutation carriers after RRSO. An estimated 60% of our cohort continues to receive care at UCSF after RRSO and the results in this report should be taken in that context. Practices described as “standard” in the UCSF Gynecologic Oncology Practice have only recently become so as the result of this survey and our clinical experience. The strategies and treatments were not uniform practice for the patients included in
Conflict of interest statement
The authors declare that there are no conflicts of interest.
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