BRCA Carriers,Prophylactic Salpingo-Oophorectomy and Menopause: Clinical Management Considerations and Recommendations

Abstract

Women who inherit a mutation in either the BRCA1 or BRCA2 gene have greatly elevated lifetime risks of ovarian cancer, fallopian tube cancer and breast cancer. Preventive surgical removal of the ovaries and fallopian tubes (salpingo-oophorectomy) is recommended to these women, often prior to natural menopause, to prevent cancer. The ensuing hormone deprivation may impact on health and quality of life. Most of these women experience menopausal symptoms shortly after surgery; however, there may also be longer term consequences that are less well understood. In this review, we highlight recent studies that examine the implications of salpingo-oophorectomy on health and quality of life in BRCA-positive women and we discuss the care of women following prophylactic surgery.

Keywords

prophylactic salpingo-oophorectomy surgical menopause

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Release date: 31 August 2012; Expiration date: 31 August 2013

Learning objectives

Upon completion of this activity, participants should be able to:

Analyze the risk of cancer associated with the BRCA mutation

Assess the benefits of prophylactic salpingo-oophorectomy among women with the BRCA mutation

Describe appropriate measures to improve bone health after salpingo-oophorectomy

Evaluate the use of hormonal therapy after salpingo-oophorectomy

Approximately 3% of women with a BRCA1 mutation are diagnosed with ovarian or fallopian tube cancer by the age of 40 years in the absence of intervention and 21% are diagnosed by the age of 50 years [1,2]. Breast cancer is diagnosed in up to 50% of BRCA1-positive women by age 50 years [2,3]. The breast cancer risk for BRCA2 is similar, but on average the cancers are diagnosed at a later age. The risk of ovarian and fallopian tube cancer is lower in BRCA2-mutation carriers than in BRCA1 carriers (approximately 20 vs 40%) [1,3]. These risks are significantly higher than the lifetime risks for breast and ovarian cancer in the general population (12 and 1.4%, respectively) [101]. Published clinical guidelines outline options for surveillance, chemoprevention and surgical prevention of cancer in these women [4,5].

Surveillance for ovarian and fallopian tube cancer has not been proven to be effective. For this reason, prophylactic salpingo-oophorectomy is actively recommended to BRCA-positive women by the age of 40 years, which results in abrupt surgical menopause. Increased vasomotor symptoms in the majority and a decline in sexual function in a substantial proportion are observed shortly after surgery and these effects may not be fully mitigated by HRT [6 –8]. A prior diagnosis of breast cancer limits options for management of menopausal symptoms because systemic HRT is generally contraindicated after breast cancer [9].

There are no published guidelines specifically for the management of BRCA-mutation carriers after prophylactic salpingo-oophorectomy. In the general population, studies of surgical menopause in young women have demonstrated increased risks for cardiovascular disease, low bone density and, in one study, an increase in cognitive impairment was observed [10 –20]. Some protection was derived from hormone therapy in these studies. These findings may be of particular importance for women who carry a BRCA mutation, as they typically undergo surgery at a young age. In addition, recent data has implicated the BRCA1 gene product as an adaptive response molecule in cardiac function. Shukla et al. suggest that women who carry a mutation in this gene may also be at an unrecognized risk for cardiovascular disease [21].

Due to these side effects, there are questions regarding the optimal age for surgery and the safety of hormone therapies, including estrogen, progesterone and androgens. The possibility of bilateral salpingectomy with ovarian retention has been raised as an interim measure for risk reduction, based on the theory that gynecologic cancer in BRCA-positive women often originates in the fallopian tube [22]. While this provisional option would maintain ovarian function, its effectiveness is unproven, and the substantial decrease in breast cancer risk would not be achieved. There is little published information regarding the appropriate care for BRCA-positive women after prophylactic salpingo-oophorectomy. In this review, recent studies which examine the implications of salpingo-oophorectomy on health in BRCA-positive women are highlighted and the care of these women after prophylactic surgery are discussed.

Prophylactic salpingo-oophorectomy

Prophylactic salpingo-oophorectomy is the complete surgical removal of the ovaries and fallopian tubes for the prevention of cancer. The uptake of this surgery ranges from 60 to 90% among BRCA carriers and uptake is related to age, the perception of cancer risk and the perceived benefit of surgery [23 –27]. This surgery reduces the risk of ovarian/fallopian tube cancer by 75–96% and of breast cancer by approximately 50%, if performed prior to natural menopause [28 –34]. Surgery does not eliminate the risk of gynecologic cancer; the residual risk for primary peritoneal cancer after prophylactic surgery has been estimated to be between 2 and 4% and may reflect the propensity of the peritoneal tissue to undergo malignant transformation [31,35,36]. This risk for cancer may also result from untreated occult microscopic tubal or ovarian disease, which presents as primary peritoneal cancer following surgery. There is no evidence to support screening with cancer antigen-125 blood test for primary peritoneal cancer after prophylactic salpingo-oophorectomy.

Occult (clinically undetected) cancers have been found at the time of prophylactic surgery in 2–18% of women who undergo preventive surgery [30,36 –46]. The rate of occult cancer detection depends on age at surgery and rigor of pathological review. Numerous authors have emphasized the need for a rigorous pathologic examination of the removed tissue because many occult cancers are microscopic [38, 39, 47 –51]. Serial sectioning of ovarian and fallopian tissue every 2–3 mm and thorough examination for microscopic disease is recommended [36,38,51,52]. Medeiros et al. describe this protocol as SEE-FIM (sectioning and extensively examining the fimbria) as the fimbria appears to be the preferred site of origin of these cancers [53]. Their protocol entails bisecting the tube at the fimbriated end and then sectioning the fimbria longitudinally, with the remainder of the fallopian tube sectioned in 2–3 mm intervals [53,54]. This is based on the premise that detection and treatment of these often microscopic early-stage lesions will decrease the rate of recurrence and death if treated appropriately.

The fallopian tube, specifically the fimbria, has been the subject of many studies examining early events in pelvic serous carcinoma, and has been posited as the origin of gynecologic cancers in BRCA carriers [39,41,52,54 –56]. Clinicopathologic and molecular studies have led to the development of a hypothesis regarding the origin of ovarian cancers that separates the disease into two distinct types that develop along different molecular pathways. Within this hypothesis, type I tumors are typically low grade and may arise from borderline tumors and endometriosis and include low-grade serous, low-grade endometrioid, clear cell and mucinous carcinomas and Brenner tumors [56]. They typically lack TP53 mutations. Type II tumors are high grade and are often of serous histology. They also include high-grade endometrioid, malignant mixed mesodermal tumors and undifferentiated carcinomas. These type II tumors have a high frequency of TP53 mutations and are associated with BRCA mutations. They are thought to develop outside the ovary, specifically in the fallopian tube and the peritoneum and involve the ovary secondarily [57]. If the theory of the fallopian tube as the tissue of origin for these high-grade serous cancers is proven, then approach to prevention in high-risk women through salpingectomy alone may be warranted [56].

Based on this model, bilateral salpingectomy or removal of the fallopian tubes with retention of the ovaries has been proposed as an interim option to reduce the risk of gynecologic cancer risk while preserving ovarian function [22,56,58]. However, the effectiveness of removing the fallopian tubes is unknown, and women who delay oophorectomy will not achieve the same reduction in breast cancer risk attributable to the decrease in circulating hormones [32]. Prophylactic salpingo-oophorectomy will likely continue to be the mainstay of prevention until a formal evaluation of salpingectomy is conducted. It has been proposed that a randomized trial will answer this question, but such a study would have to be large and women would have to be willing to be randomized. The approximate incidence of ovarian, fallopian tube or peritoneal cancer is 1% per year in carriers with ovaries and tubes intact. The risk of peritoneal cancer is 0.2% per year after salpingo-oophorectomy [31]. Therefore, among 500 women followed for 5 years after salpingectomy, approximately five cancers will be diagnosed if the procedure is equally effective as salpingo-oophorectomy, whereas up to 25 cases will occur if the procedure is not as effective.

Quality of life after salpingo-oophorectomy: menopausal symptoms & sexual function

One of the first studies to evaluate quality of life after prophylactic oophorectomy for a family history of ovarian cancer was published in 2001 by Elit et al. [6]. They found that overall quality of life was comparable with that of the general population, but menopause-specific quality of life was lower and satisfaction with sexual functioning was compromised in 54% of women at a mean of 5 years after surgery. In a retrospective study of 59 women who underwent prophylactic surgery, Robson et al. found overall quality of life to be comparable with that of the general population at a mean of 2 years after surgery [7]. However, 35% of participants reported vaginal dryness as ‘quite a bit’ or ‘extremely’ bothersome and 28% of participants reported dyspareunia or ‘pain with sex’ to be bothersome.

Madalinska et al. published cross-sectional studies in 2005 and 2006 [59,60]. The first compared women who elected to have prophylactic salpingo-oophorectomy with women who chose screening [59]. Women in this study ranged in age from 30 to 75 years. Women in both groups had quality of life scores similar to those of the general population. However, women who had surgery reported more menopausal symptoms, more vaginal dryness and dyspareunia, and less pleasure and satisfaction during sexual activity [59]. The second study included only premenopausal women and compared women who had undergone salpingo-oophorectomy with women who were having gynecologic screening [60]. Among women who underwent surgery, those who took HRT reported significantly fewer menopausal symptoms than women who did not take HRT (p < 0.05) [60]. However, women who had surgery and took HRT experienced significantly more menopausal symptoms than women in the screening group (p < 0.05; i.e., HRT did not entirely mitigate menopausal symptoms). These symptoms included hot flashes, cold and hot sweats, vaginal dryness, pain with intercourse and loss of interest in sex.

There are a few prospective studies evaluating the short-term impact of prophylactic salpingo-oophorectomy on vasomotor symptoms and sexual function. Fang et al. found that women in the surgical group reported more hot flashes and vaginal dryness compared with women undergoing screening [61]. While the frequency of sexual activity decreased in the month after surgery in the surgical group, it returned to usual levels 1 year after surgery. A study by the authors' group found that women who were premenopausal at the time of surgery experienced a worsening of hot flashes, night sweats and sweating and a decline in sexual function 1 year after surgery [8]. Women who took HRT experienced fewer and less severe hot flashes and significantly less vaginal dryness and sexual discomfort than did women who did not take HRT after surgery. However, HRT did not prevent decline in sexual pleasure after surgery. Despite the increase in vasomotor and sexual symptoms related to surgical menopause, most women reported a high level of satisfaction with the decision to undergo prophylactic salpingo-oophorectomy. Physical and mental health-related quality of life was similar to that of population controls, before and after surgery [62].

In a study of information needs of BRCA-positive women who underwent salpingo-oophorectomy, 59% of women stated that they would have found it helpful to have had more information about the impact of this surgery on their sex life and 57% would have liked more information about the availability of sex counseling [63].

Bone health

Premenopausal oophorectomy is associated with an increased risk of osteopenia and osteoporosis, most likely resulting from endogenous estrogen deficiency [10,64,65]. After bilateral oophorectomy, loss of trabecular bone has been reported to be as high as 20 % during the first 18 months following surgery [66]. Aitken et al. compared 163 women who underwent hysterectomy and oophorectomy with 95 women who underwent hysterectomy alone [64]. Oophorectomy before the age of 45 years was associated with an increased prevalence of osteoporosis within 6 years of surgery. Risk for fracture is also substantially increased in women who undergo oophorectomy prior to age 45 years (odds ratio [OR]: 3.64; 95% CI: 1.01–13.04) compared with women who undergo surgery after age 45 years, with the use of HRT mitigating this risk [10].

There are few longitudinal studies that examine the effect of premenopausal oophorectomy on bone health. Yoshida et al. evaluated changes in bone density and lipid levels in a prospective study, comparing 35 surgically menopausal women to 27 non-oophorectomized controls. Bone mineral density was decreased by as much as 6.7% at 12 months in the oophorectomized group of women – a rate of loss that is much greater than observed in natural menopause [67]. No change was observed in the control women.

Several recent cross-sectional studies have examined bone health after salpingo-oophorectomy in women with a BRCA mutation. Cohen et al. published a study of 226 BRCA carriers after salpingo-oophorectomy [68]. Bone density measurements after surgery were available for 152 women of whom 108 (71%) had abnormal bone density (57% osteopenia, 14% osteoporosis). Among women who underwent surgery before the age of 50 years, high rates of osteopenia (62%) and osteoporosis (9%) were reported. They compared women who underwent surgery before 50 years of age and after 50 years of age and found similar bone densities in both groups, despite a mean age difference of 16 years (mean age: 44.7 vs 60.6) [68]. In a recent retrospective study by Challberg et al., only 36% of 210 women who underwent prophylactic salpingo-oophorectomy before the age of 49 years had undergone a bone density evaluation after surgery (median age at surgery of 41 years) [11]. They reported that after evaluation with dual-energy X-ray absorptiometry (DXA), women who experienced ≥24 months of estrogen deprivation had a much higher prevalence of reduced bone mass, consistent with osteopenia and osteoporosis, when compared with women who took HRT for any period before the age of 50 years (46 vs 16%). This strengthens the case for routine assessment of bone density and postoophorectomy hormone replacement in women who are under the age of 50 years at surgery; however, the duration of HRT use required is not known [69,70].

Chapman et al. also evaluated postsurgical surveillance, including bone density measurement, with DXA testing and found that 75% of women had a history of bone density measurement, of whom 23% had osteopenia and 10% had osteoporosis [71]. They attribute inconsistencies in care after surgery to the lack of guidelines for postsurgical care, and called for the development of national guidelines.

Clinical evaluation of bone density by DXA is indicated for women who have menopause before 45 years of age, according to the clinical practice guidelines in Canada [72]. As bone density has been shown to decrease substantially during the first 2 years after surgical menopause, a baseline bone density measurement at the time of surgery and another measurement 1–2 years following surgery may help to identify women who are at greater risk for osteoporosis and fractures [11,66,67]. Referral to an osteoporosis specialist may be warranted for possible treatment. Change in diet alone is not sufficient to prevent bone loss in women with early menopause [73]. A discussion of the role of exercise in the maintenance of bone health, and a calcium intake of 1500 mg/day from dietary and supplemental sources and supplementation of 800 IU/day of vitamin D is recommended for women after menopause [74].

Cardiovascular health

A positive association between bilateral oophorectomy and increased risk of cardiovascular disease has been observed in a number of observational studies, including the Nurse's Health Study and the Mayo Clinic Cohort of Oophorectomy and Aging [12,13,75]. The Nurse's Health Study reported on the relationship of menopause (natural and surgical) and the subsequent risk of coronary heart disease in 121,700 women between 30 and 55 years of age [13]. After controlling for age and cigarette smoking, women who had a natural menopause (with or without estrogen replacement) did not have an increased occurrence of coronary heart disease. However, women who underwent bilateral oophorectomy who had never taken a hormone replacement had an increased risk of cardiovascular disease, compared with women with intact ovaries (rate ratio: 2.2; 95% CI: 1.2–4.2) [13]. The Mayo Clinic Cohort of Oophorectomy and Aging reported that women who underwent bilateral oophorectomy before the age of 45 years experienced increased mortality due to cardiovascular disease, compared with referent women (hazard ratio [HR]: 1.44; 95% CI: 1.01–2.05; p = 0.04). The risk was higher for those not treated with estrogen (HR: 1.84; 95% CI: 1.27–2.68; p = 0.001) than for those treated with estrogen (HR: 0.65; 95% CI: 0.30–1.41; p = 0.28) [12]. In a meta-analysis by Atsma et al., natural menopause did not increase the risk for cardiovascular disease, whereas bilateral oophorectomy before the age of 50 years did (relative risk: 4.55; 95% CI: 2.56–8.10) [75].

It appears then that HRT mitigates the increase in cardiovascular risk associated with surgical menopause [12 –14]. Recent results from the Women's Health Initiative (WHI) found that neither estrogen alone nor estrogen plus progesterone reduced the risk of cardiovascular disease [76]. However, the women in the WHI were, on average, aged 62-years-old at randomization and few had undergone oophorectomy and, therefore, are not representative of young women who experience surgical menopause.

A possible increased risk of ischemic stroke related to early surgical menopause should also be considered [15,16]. Rocca et al. reviewed observational studies of menopause, estrogen use and ischemic stroke [16]. While exogenous estrogen appears to be a risk factor for ischemic stroke after natural menopause, estrogen therapy before the age of 50 years appears to decrease the risk of ischemic stroke in women who undergo early surgical menopause [15 –19].

Kritz-Silverstein et al. compared biomarkers of cardiac risk among 1150 women who were approximately 20 years postmenopause [77]. They found that women who had menopause due to bilateral oophorectomy had increased lipids, lipoproteins, glucose and insulin levels compared with the women with hysterectomy alone, factors that are thought to account for an increase in cardiovascular disease risk [77 –79]. Yoshida et al. also measured the impact of surgical menopause on lipid levels in a prospective study and found significant elevation in the level of low-density lipoprotein in surgically menopausal women compared with their baseline level; a similar change was not observed in non-oophorectomized controls [67]. These changes were observed as early as 6–12 months after surgical menopause. These authors suggest that oophorectomized patients require monitoring for lipid metabolism [67].

A recent publication by Shukla et al. links BRCA1 gene function with cardiovascular function. This group demonstrated that the BRCA1 gene product works to prevent DNA damage, cardiomyocyte apoptosis and heart dysfunction in mice [21]. The authors demonstrated that loss of BRCA1 in cardiomyocytes resulted in adverse cardiac remodeling, poor ventricular function and increased mortality in response to ischemic or genotoxic stress. They also observed reduced cardiac performance, and enhanced cardiomyocyte death in response to genotoxic stress (i.e., treatment with doxorubicin). In human adult heart tissue, they showed that ischemia induced double-strand breaks and upregulated BRCA1 expression [21]. They posit that BRCA1-positive women may be at an increased risk for cardiovascular disease that has not yet been recognized. However, there are no clinical studies to date to evaluate this.

Cognitive function

Cognitive function has been examined in women in the general population who have undergone oophorectomy for benign conditions [20,80 –83]. The Mayo Clinic Cohort of Oophorectomy and Aging examined cognitive function described as the presence of dementia, senility, Alzheimer's disease or difficulty with daily living caused by cognitive problems. The median follow-up in both the oophorectomized and referent groups was greater than 25 years after menopause. The risk of cognitive impairment or dementia later in life appeared to be increased in women who underwent oophorectomy before menopause, compared with women who did not (HR: 1.46; 95% CI: 1.13–1.90). The greatest risk was observed in women who underwent bilateral oophorectomy before 49 years of age and who were not treated with estrogen until at least 50 years of age (HR: 1.89; 95% CI: 1.27–2.83) [20].

HRT: is it safe?

The main concern of women considering systemic HRT is that it may increase their risk of breast cancer. Two observational studies of HRT after prophylactic salpingo-oophorectomy in women who carry a BRCA mutation showed no increase in breast cancer risk [84,85]. In addition, HRT may provide some benefit for the management of the effects of surgical menopause, such as an increase in vasomotor symptoms, a decrease in bone density and decreases in cardiovascular health and cognitive function, observed in young women who undergo surgical menopause in their early forties [8,10 –19,60]. However, current studies of HRT in BRCA-positive women are nonrandomized and there is little data pertaining to women who are BRCA2 positive. The long-term effect of hormone therapy in BRCA-positive women is unknown and further studies are needed.

Data from studies of women in the general population have generated concern about a possible increase in risk of breast cancer with HRT [86]. The WHI study found that women who took combination HRT (estrogen and progesterone combination therapy) had a higher risk of breast cancer compared with women who received placebo (HR: 1.26; 95% CI: 1.02–1.55) [87]. Among postmenopausal women with prior hysterectomy, use of estrogen alone for 5.9 years was associated with a decrease in risk of breast cancer after a follow-up for more than 10 years (HR: 0.77; 95% CI: 0.62–0.95) [88,89]. It is important to note that women in this study were aged 50–79 years and approximately 80% were ≥5 years beyond menopause when they were randomized. The Million Women Study confirmed the increase in risk with both past and current combined HRT use, but also observed a modest increase in risk with the use of estrogen alone, which may be related to the timing of use [90,91]. These findings do not necessarily apply to surgically menopausal young women and care must be taken not to dismiss the possible benefits of hormone replacement in these women.

HRT (consisting of estrogen alone or combined therapy) alleviates symptoms such as vaginal dryness and dyspareunia, but it may not lessen the decline in sexual function, such as decreased libido, experienced by some after surgical menopause [8]. Androgen replacement therapy may be helpful here [8,92 –94]. However, there is no data confirming the safety of androgens in BRCA-positive women. Several studies demonstrate a positive relationship between higher levels of endogenous androgens and breast cancer risk (as reviwed in [95]). Studies of exogenous testosterone use and the risk of breast cancer in the general population are mixed. The Nurses' Health Study found an increase in breast cancer risk among current users of estrogen and testosterone (relative risk: 2.48; 95% CI: 1.53–4.04) [96]. The results from the WHI also suggested an increase in risk (HR: 1.42; 95% CI: 0.95–2.11), however, they were not significant [97]. A recent case–control study found an increased risk of breast cancer for women who took conjugated estrogen plus progestin (OR: 1.44; 95% CI: 1.31–1.58; 712 cases and 2087 controls), but not esterified estrogen with methyltestosterone (OR: 1.08; 95% CI: 0.86–1.36; 98 cases and 380 controls) [98]. Interestingly, there was an increased risk observed in women who took esterified estrogen with methyltestosterone plus progestin (OR: 1.69; 95% CI: 1.03–2.79; 22 cases and 55 controls). Davis et al. suggested a difference in the risk related to the route of administration, with some studies of oral testosterone demonstrating an increase in risk, whereas two studies of parenteral testosterone use (with implant) have not [99].

Executive summary

Inquiry into menopausal symptoms, such as hot flashes, night sweats, sweating and sleep disturbances.

Discussion regarding sexual function including vaginal dryness, dyspareunia and changes in libido.

Review of options for management of these symptoms.

Bone density

Bone density measurement with dual-energy X-ray absorptiometry at the time of salpingo-oophorectomy and again 1–2 years after surgery. Timing of further bone density measurements should be individualized based on the results of these two measurements and use of pharmacologic agents to prevent or treat osteoporosis.

Discussion regarding the role of exercise in bone health. A recommended daily intake of 1500 mg calcium from dietary and supplemental sources and supplementation with 800 IU/day of vitamin D daily is suggested.

Referral to an osteoporosis specialist for women with osteopenia or osteoporosis or a clinically significant decrease in bone density during the interval between measurements.

Cardiovascular health

Regular measurement of blood pressure and blood lipid levels including low-density lipoprotein, high-density lipoprotein and total cholesterol and blood glucose levels beginning 1 year after surgery. Refer as appropriate.

Discussion regarding the importance of physical exercise, healthy bodyweight and smoking cessation in cardiovascular health.

Hormone replacement therapy

The risk of breast cancer is a concern when considering any systemic HRT regimen for a woman who carries a BRCA mutation. Women will either be at high risk for breast cancer (breasts intact), low risk for breast cancer (prophylactic mastectomy) or have a prior diagnosis of breast cancer.

BRCA1-positive woman with breasts intact, no previous breast cancer:

– HRT (combined estrogen and progesterone for women with salpingo-oophorectomy only, estrogen alone for women with hysterectomy and salpingo-oophorectomy) may be offered after prophylactic salpingo-oophorectomy to the age of natural menopause (age 50–52 years);

– There is insufficient evidence to determine the safety of androgen replacement therapy after salpingo-oophorectomy in BRCA-positive women;

– If taking tamoxifen or raloxifene, for osteoporosis prevention or for reduction of breast cancer risk, HRT should not be prescribed.

BRCA2-positive woman with breasts intact, no previous breast cancer:

– HRT (combined estrogen and progesterone for women with salpingo-oophorectomy only, estrogen alone for women with hysterectomy and salpingo-oophorectomy) may be considered after prophylactic salpingo-oophorectomy. There is limited data regarding the safety of hormone replacement in women who are BRCA2-positive;

– There is insufficient evidence to determine the safety of androgen replacement therapy after salpingo-oophorectomy in BRCA-positive women;

– If taking tamoxifen or raloxifene, for osteoporosis prevention or for reduction of breast cancer risk, HRT should not be prescribed.

BRCA-positive woman with prior breast cancer:

– Systemic HRT is generally contraindicated for women with a previous diagnosis of breast cancer. Local vaginal estrogens may be considered;

– Consider selective serotonin reuptake inhibitors or selective serotonin-norepinephrine reuptake inhibitors for the management of vasomotor symptoms.

BRCA-positive woman with prophylactic mastectomy, no previous breast cancer:

– HRT (combined estrogen and progesterone for women with salpingo-oophorectomy only, estrogen alone for women with hysterectomy and salpingo-oophorectomy) should be offered after prophylactic salpingo-oophorectomy to the age of natural menopause;

– Androgen replacement therapy may be considered with discussion of possible side effects.

Conclusion & future perspective

The appropriate management of BRCA-positive women who elect to undergo prophylactic salpingo-oophorectomy is an important clinical issue. The National Comprehensive Cancer Network guidelines state that the increased risk of osteoporosis and cardiovascular disease associated with premature menopause should be addressed, as well as possible effects of cognitive changes and vasomotor symptoms on quality of life; counseling also includes a discussion of possible short-term HRT to a recommended maximum age of natural menopause [4]. The authors propose specific guidelines for the appropriate care of BRCA-positive women after prophylactic salpingo-oophorectomy. In addition, these women would benefit from a model of integrated multidisciplinary clinical care to ensure that all aspects of care are appropriately addressed in a timely manner. Further studies are needed to evaluate the management of young BRCA-positive women who elect to undergo prophylactic salpingo-oophorectomy.

Footnotes

Acknowledgements

The authors would like to thank P Harvey (Women's College Hospital, Toronto, ON, Canada) and N Kauff (Memorial Sloan-Kettering Cancer Center, NY, USA) for their critical reading of the manuscript.

CME Author

Charles P Vega, Health Sciences Clinical Professor; Residency Director, Department of Family Medicine, University of California, Irvine, CA, USA

Disclosure: Charles P Vega has disclosed no relevant financial relationships.

Authors and Disclosures

Amy Finch, Women's College Research Institute, Women's College Hospital, 790 Bay Street, Suite 700, Toronto, ON, M5G 1N8, Canada

Disclosure: Amy Finch would like to acknowledge the support of the Ontario Postdoctoral Fellowship through the Ontario Ministry of Research and Innovation and Women's College Hospital.

Gareth Evans, Department of Genetic Medicine, The University of Manchester, Manchester Academic Health Science Centre, Manchester, UK

Disclosure: Gareth Evans has disclosed no relevant financial relationships.

Steven A Narod, Women's College Research Institute, Women's College Hospital, 790 Bay Street, Suite 700, Toronto, ON, M5G 1N8, Canada

Disclosure: Steven A Narod has disclosed no relevant financial relationships.

Editor

Elisa Manzotti, Publisher, Future Science Group

Disclosure: Elisa Manzotti has disclosed no relevant financial relationships.

BRCA carriers,prophylactic salpingo-oophorectomy and menopause

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