Comprehensive Care of Women With Genetic Predisposition to Breast and Ovarian Cancer.

Women at risk for hereditary breast and ovarian cancer syndromes are frequently seen in primary care and gynecology clinics. They present with a distinctive set of clinical and emotional needs that revolve around complex risk management discussions and decision making. The care of these women calls for the creation of individualized care plans that facilitate adjustment to the mental and physical changes associated with their choices. This article provides an update on comprehensive evidence-driven care of women with hereditary breast and ovarian cancer. The aim of this review is to aid clinicians in identifying those at risk for hereditary cancer syndromes and provide practical advice on patient-centered medical and surgical risk management. Topics of discussion include enhanced surveillance, preventive medications, risk-reducing mastectomy and reconstruction, risk-reducing bilateral salpingo-oophorectomy, fertility, sexuality, and menopausal management, with attention to the importance of psychological support. High-risk patients may benefit from a multidisciplinary team that provides realistic expectations with consistent messaging. The primary care provider must be aware of the special needs of these patients and the consequences of their risk management interventions.

Evaluation of a patient decision aid for BRCA1/2 pathogenic variant carriers choosing an ovarian cancer prevention strategy.

OBJECTIVE: Risk-reducing surgery is advised to BRCA1/2 pathogenic variant (PV) carriers around the age of 40 years to reduce ovarian cancer risk. In the TUBA-study, a multicenter preference study (NCT02321228), BRCA1/2-PV carriers are offered a choice: the standard strategy of risk-reducing salpingo-oophorectomy or the novel strategy of risk-reducing salpingectomy with delayed oophorectomy. We evaluated feasibility and effectiveness of a patient decision aid for this choice. METHODS: Premenopausal BRCA1/2-PV carriers were counselled for risk-reducing surgical options in the TUBA-study; the first cohort was counselled without and the second cohort with decision aid. Evaluation was performed using digital questionnaires for participating women and their healthcare professionals. Outcome measures included actual choice, feasibility (usage and experiences) and effectiveness (knowledge, cancer worry, decisional conflict, decisional regret and self-estimated influence on decision). RESULTS: 283 women were counselled without and 282 women with decision aid. The novel strategy was chosen less frequently in women without compared with women with decision aid (67% vs 78%, p = 0.004). The decision aid was graded with an 8 out of 10 by both women and professionals, and 78% of the women would recommend this decision aid to others. Users of the decision aid reported increased knowledge about the options and increased insight in personal values. Knowledge on cancer risk, decisional conflict, decisional regret and cancer worry were similar in both cohorts. CONCLUSIONS: The use of the patient decision aid for risk-reducing surgery is feasible, effective and highly appreciated among BRCA1/2-PV carriers facing the decision between salpingo-oophorectomy or salpingectomy with delayed oophorectomy.

What happens after menopause? (WHAM): A prospective controlled study of depression and anxiety up to 12 months after premenopausal risk-reducing bilateral salpingo-oophorectomy.

OBJECTIVE: Risk-reducing bilateral salpingo-oophorectomy (RRBSO) substantially reduces ovarian cancer risk in women with pathogenic gene variants and is generally recommended by age 34-45 years. Natural menopause is a vulnerable period for mood disturbance, but the risk of depression and anxiety in the first 12 months after RRBSO and potential modifying effect of hormone therapy are uncertain. METHODS: Prospective controlled observational study of 95 premenopausal women planning RRBSO and a Comparison group of 99 premenopausal women who retained their ovaries,- 95% of whom were at population level risk of ovarian cancer. Clinically significant symptoms of depression and anxiety were measured using standardised instruments at baseline, 3, 6 and 12 months. Chi-square tests and adjusted logistic regression models compared differences between groups. RESULTS: Baseline symptoms and previous depression or anxiety did not differ between groups. At 3 months after RRBSO clinically significant depressive symptoms were doubled (14.5% vs 27.1%, p = 0.010), which persisted at 12 months. Depressive symptoms were stable in comparisons. At 3 months after RRBSO, clinically significant anxiety symptoms almost trebled (6.1% vs 17.7%, p = 0.014) before plateauing at 6 months and returning to baseline at 12 months. Compared to comparisons, RRBSO participants were at 3.0-fold increased risk of chronic depressive symptoms (Wald 95% CI 1.27-7.26), 2.3-fold increased risk of incident depression (95% Wald CI 1.08-5.13) and 2.0-fold increase of incident anxiety (Wald 95% CI 0.78-5.00). Depression and anxiety were slightly more common in Hormone Therapy users after RRBSO vs non-users. CONCLUSIONS: RRBSO leads to a rapid increase in clinically significant depressive and anxiety symptoms despite Hormone Therapy use.

The impact of bilateral salpingo-oophorectomy on sexuality and quality of life in women with breast cancer.

OBJECTIVE: To compare sexual function and quality of life (QoL) in breast cancer survivors with and without a history of bilateral salpingo-oophorectomy (BSO). METHODS: A cross-sectional study of breast cancer survivors treated at a tertiary referral hospital in Western Australia. The Female Sexual Function Index was used to determine rates of female sexual dysfunction (FSD) and hypoactive sexual desire disorder (HSDD). Participants also completed the Relationship Assessment Scale, Menopause-specific quality of life questionnaire and Short Form Health Survey-36. RESULTS: A total of 427 women were invited to participate: 119 had undergone BSO and 308 were controls with at least one ovary remaining. A total of 172 women participated (overall response rate 40.3%), consisting of 76 women in the BSO group (response rate 63.9%) and 96 women with at least one ovary remaining (response rate 31.2%). There was no difference in FSD between the two groups: 63/76 (82.9%) women who had undergone BSO had FSD compared to 75/96 (78.1%) controls (p = 0.458). No difference in HSDD was observed (p = 0.084) between the BSO group 70/76 (96.0%) and the controls 96/96 (100%). Women who had undergone BSO had lower general health scores compared to the control group (p = 0.034). Both groups had similar energy levels, emotional well-being, pain scores, physical functioning levels and social functioning levels. CONCLUSIONS: In this study, women with prior treatment for breast cancer had high levels of FSD and HSDD, irrespective of whether they had undergone BSO. Both groups reported similar sexual function scores and QoL.

Exploring factors that impact uptake of risk-reducing bilateral salpingo-oophorectomy (RRBSO) in high-risk women.

OBJECTIVE: Only risk-reducing bilateral salpingo-oophorectomy (RRBSO) has been shown to reduce ovarian cancer deaths in high-risk women. Uptake of RRBSO is, however, suboptimal and reasons are not well defined. More information is needed about the barriers to RRBSO and patient needs for information and care. METHODS: Cross-sectional study including the Perception of Cancer Risk Scale, factors affecting decision-making about RRBSO, and unmet information needs were measured using a purpose-designed questionnaire. RESULTS: Of the 193 high-risk women aged 30 to 50 approached, 60 (31%) agreed to participate. Respondents were either considering or had recently undergone premenopausal RRBSO. Most (49/60) had no personal history of cancer; 11/60 had previous breast cancer. Overall, responses did not differ between pre- and post-RRBSO participants. The main barriers to RRBSO were surgical menopause and loss of fertility. Other concerns included the impact on sexual function and bone health. Reduction in ovarian cancer risk and prolonged life expectancy were the main drivers for RRBSO. Participants understood that RRBSO reduced cancer risk, although most substantially overestimated their personal ovarian cancer risk. High-risk women wanted more information about how to manage the short- and long-term consequences of surgical menopause. CONCLUSIONS: Concerns about surgical menopause and loss of fertility are barriers to RRBSO for high-risk women despite understanding the benefits of reduced cancer risk. There is an unmet need for more information about effectively managing the noncancer consequences of RRBSO in premenopausal women. : Video Summary:http://links.lww.com/MENO/A478.

Prospective follow-up of quality of life for participants undergoing risk-reducing salpingo-oophorectomy or ovarian cancer screening in GOG-0199: An NRG Oncology/GOG study.

BACKGROUND: Risk-reducing salpingo-oophorectomy (RRSO) and ovarian cancer screening (OCS) are management options for women at increased risk of ovarian cancer. Long-term effects of these interventions on quality of life (QOL) are not well understood. METHODS: GOG-0199 is a prospective cohort study of women at increased ovarian cancer risk who chose either RRSO or OCS as their risk management intervention. At study entry, 6, 12, 24 and 60 months of follow-up, participants completed the QOL questionnaire, which included the Medical Outcome Study Short Form-36, the Impact of Events Scales, the Center for Epidemiological Studies Depression Scale, the State-Trait Anxiety Inventory, the Functional Assessment of Cancer Therapy - Endocrine Subscale, and the Sexual Activity Questionnaire. QOL measures were compared between the RRSO and OCS cohort at baseline and over time. RESULTS: Five-hundred-sixty-two participants in the RRSO cohort and 1,010 in the OCS completed the baseline and at least one follow-up questionnaire. At baseline, participants selecting RRSO reported lower health-related QOL (HRQOL), greater ovarian cancer-related stress, greater anxiety, and more depressive symptomatology, which improved during follow-up, especially for ovarian cancer-related stress. Screening was not found to adversely impact HRQOL. Hormone-related menopausal symptoms worsened and sexual functioning declined during follow-up in both cohorts, but more so among participants who underwent RRSO. CONCLUSIONS: HRQOL improved after surgery among women who chose RRSO and remained stable among participants undergoing screening. The adverse effects of RRSO and screening on short-term and long-term sexual activity and sexual functioning warrant consideration in the decision-making process for high-risk women.

Does preventive oophorectomy increase the risk of depression in BRCA mutation carriers?

OBJECTIVE: BRCA mutation carriers are advised to undergo bilateral salpingo-oophorectomy to prevent ovarian cancer. The abrupt hormonal withdrawal associated with early surgical menopause has been shown to increase the risk of depression and anxiety among women in the general population. The impact in women with a BRCA1 or BRCA2 mutation is not known. METHODS: We undertook a matched prospective study of BRCA mutation carriers to evaluate the impact of oophorectomy on self-reported initiation of antidepressant use. We identified women with no personal history of cancer or depression and prospectively evaluated the frequency of self-reported medication use after surgery. Each exposed participant (oophorectomy) was randomly matched to a control participant (no oophorectomy) according to year of birth (within 3 years), BRCA mutation type (BRCA1 or BRCA2), and country of residence (Canada, United States, Poland). A total of 506 matched sets were included. We estimated the odds ratio (OR) and 95% confidence intervals (CIs) of antidepressant use (ever/never) following preventive oophorectomy in the entire study population and stratified by age at oophorectomy and by use of hormone therapy. RESULTS: Oophorectomy was not associated with more frequent antidepressant use among BRCA mutation carriers (OR = 0.46; 95% CI 0.22-0.96). We observed reductions in the odds of antidepressant medication use among women who underwent oophorectomy before the age of 50 years (OR = 0.33; 95% CI 0.14-0.78) and among those who initiated hormone therapy use after oophorectomy (OR = 0.35; 95% CI 0.14-0.90). Findings were similar when the analysis was based on self-reported depression (rather than antidepressant use). CONCLUSIONS: Although based on a small number of women, these findings suggest that oophorectomy does not increase psychological distress among women at an elevated risk of ovarian cancer.

The Effect of Prophylactic Adnexectomy on the Quality of Life and Psychosocial Functioning of Women with the BRCA1/BRCA2 Mutations.

The main purpose of this study was to analyze the effect of risk-reducing salpingo-oophorectomy (RRSO) on the quality of life (QoL) and psychosocial functioning of patients with the BRCA1/BRCA2 mutations. This survey-based study was conducted using the Blatt-Kupperman Index, the Women's Health Questionnaire, the Perceived Stress Scale, the State-Trait Anxiety Inventory, the Beck Depression Inventory-II, and the authors' questionnaire. All calculations were done using Statistica 13.3. The QoL after RRSO was statistically significantly lower in most domains compared with the state before surgery. The greatest decline in the QoL was observed in the vasomotor symptoms domain (d = 0.953) and the smallest in the memory/concentration domain (d = 0.167). We observed a statistically significant decrease in the level of anxiety as a state (d = 0.381), as well as a statistically significant increase in the severity of climacteric symptoms (d = 0.315) and depressive symptoms (d = 0.125). Prophylactic surgeries of the reproductive organs have a negative effect on the QoL and psychosocial functioning of women with the BRCA1/2 mutations, as they increase the severity of depressive and climacteric symptoms. At the same time, these surgeries reduce anxiety as a state, which may be associated with the elimination of cancerophobia.

Perioperative Management of Women Undergoing Risk-reducing Surgery for Hereditary Breast and Ovarian Cancer.

Carriers of genetic mutations that predispose to cancer syndromes are often faced with complex decisions. For women with hereditary breast and ovarian cancer in particular, the decision to undergo risk-reducing mastectomy or bilateral salpingo-oophorectomy is burdensome from a physical and psychological perspective. Although risk-reducing surgery is the most effective preventative measure in reducing a genetic mutation carrier's risk of breast or ovarian cancer, the success of these procedures requires a multidisciplinary approach that centers on careful counseling regarding the risks and benefits of risk-reducing surgery. The physical and psychological distress associated with risk-reducing surgery often makes a combined surgical approach attractive to some patients. In this review, we present the evidence surrounding the comprehensive surgical care of women with hereditary breast and ovarian cancer syndromes and evaluate the perioperative factors that influence surgical management.

Distinctive psychological and social experiences of women choosing prophylactic oophorectomy for cancer prevention.

Women known to have significantly elevated ovarian cancer risk due to genetic mutations or family history can reduce this risk by surgically removing both ovaries and fallopian tubes (RRBSO, risk-reducing bilateral salpingo-oophorectomy). We used interpretive phenomenological analysis (IPA) to explore the psychosocial experiences of women who chose RRBSO for cancer prevention. We extended the traditional use of IPA to compare the experiences of women who chose RRBSO for cancer prevention to those of women who underwent similar gynecologic surgery for benign indications. The analysis resulted in three superordinate themes describing women's psychosocial experiences related to RRBSO: (a) psychological facets of cancer risk (b) social support and (c) shared medical decision making. Findings illustrate that women choosing RRBSO for cancer prevention experience heightened psychosocial challenges before and after surgery compared to women undergoing surgery for benign indication. Furthermore, they may need distinct types of information and support from healthcare providers.

Short report: Follow-up of Bahamian women with a BRCA1 or BRCA2 mutation.

PURPOSE: We sought to determine to what extent the knowledge of carrying a BRCA1 or BRCA2 mutation influences the uptake of preventive surgeries in Bahamian women, including bilateral salpingo-oophorectomy and bilateral mastectomy. PATIENTS AND METHODS: The study population consisted of 78 female residents of the Bahamas for whom a BRCA1 or BRCA2 mutation had been detected between 2004 and 2014. The mean age of the 78 participants at the time of genetic testing was 46 years (age range 22-73 years). The mean time of follow-up was 4.4 years. RESULTS: Of the 78 study participants, 19 women had a bilateral salpingo-oophorectomy (24%). Seven out of 37 patients who had unilateral breast cancer chose to remove the unaffected contralateral breast (19%). Three of 13 patients with no history of breast cancer chose to have a prophylactic bilateral mastectomy (23%). CONCLUSION: Preventive surgery is an acceptable option for a significant proportion of Bahamian women with a BRCA1 or BRCA2 mutation. It will be important to identify and reduce barriers to preventive surgery in the Bahamas in order that the benefit of getting testing can be fully realized.

Putting the "No" in Non Nocere: Surgery, Anesthesia, and a Patient's Right to Withdraw Consent.

[Full article available at http://rimed.org/rimedicaljournal-2017-10.asp].

Review Article: Sexuality and Risk-Reducing Salpingo-oophorectomy.

INTRODUCTION: Women with familial cancer syndromes such as hereditary breast and ovarian cancer syndrome (BRCA1 and BRCA2) and Lynch syndrome are at a significantly increased risk of developing ovarian cancer and are advised to undergo prophylactic removal of their ovaries and fallopian tubes at age 35 to 40 years, after childbearing is complete. METHODS: A comprehensive literature search of studies on risk-reducing salpingo-oophorectomy (RRSO), sexuality, and associated issues was conducted in MEDLINE databases. RESULTS: Risk-reducing salpingo-oophorectomy can significantly impact on a woman's psychological and sexual well-being, with women wishing they had received more information about this prior to undergoing surgery. The most commonly reported sexual symptoms experienced are vaginal dryness and reduced libido. Women who are premenopausal at the time of surgery may experience a greater decline in sexual function, with menopausal hormone therapy improving but not alleviating sexual symptoms. Pharmacological treatments including testosterone patches and flibanserin are available but have limited safety data in this group. CONCLUSIONS: Despite the high rates of sexual difficulties after RRSO, patient satisfaction with the decision to undergo surgery remains high. Preoperative counseling with women who are considering RRSO should include discussion of its potential sexual effects and the limitations of menopausal hormone therapy in managing symptoms of surgical menopause.

Discussing Sexuality With Women Considering Risk-Reducing Salpingo-oophorectomy: An International Survey of Current Practice in Gynecologic Oncology.

OBJECTIVE: To determine how frequently gynecologic oncologists discuss sexuality with women considering risk-reducing salpingo-oophorectomy. Secondary objectives were to assess the availability of resources, and the barriers to discussing sexuality. METHODS: Members of the Australian Society of Gynaecologic Oncologists, International Gynecologic Cancer Society, and Society of Gynecologic Oncology were invited to complete an online survey. Questions addressed frequency of, and barriers to, discussing sexuality, and availability of resources related to sexual issues. RESULTS: Three hundred eighty-eight physicians in 43 countries responded from 4,006 email invitations (9.7%). Ninety-one percent reported discussing sexuality preoperatively, and 61% discuss it with every patient. Factors associated with higher rates of discussion were female sex (P = 0.020), higher level of training (P = 0.003), time in practice (P = 0.003), and consulting more risk-reducing salpingo-oophorectomy patients per month (P = 0.006). Commonly discussed issues were vasomotor menopausal symptoms (91%) and vaginal dryness (85%). Eighty-eight percent of respondents believed that sexuality should be discussed preoperatively, and most felt that it is their responsibility (82%). Fear of causing distress was the most common barrier to discussing sexuality (49%). Twenty-four percent felt that they did not have adequate training to discuss sexual function. CONCLUSIONS: Although most respondents believed that discussing sexuality should occur preoperatively, only 61% discuss this with every patient. Resources specifically relating to sexuality are limited. The most common barrier to discussing sexuality was fear of causing distress. Nearly one quarter of gynecologic oncologists felt inadequately trained to discuss sexual function.