Uptake Of Risk-reducing Salpingo-oophorectomy Research Articles

Decision-making for Risk-reducing Salpingo-oophorectomy (RRSO) in Southeast Asian BRCA Mutation Carriers With Breast Cancer: A Qualitative Study

The uptake of risk-reducing salpingo-oophorectomy (RRSO) in Asian countries is variable despite being the most effective option for ovarian cancer risk reduction in BRCA mutation carriers. Exploration of factors which may impact the RRSO decision-making of BRCA mutation carriers from Malaysia, a developing country in Southeast Asia, was undertaken. In-depth interviews with 28 Malaysian BRCA mutation carriers with a history of breast cancer were conducted in addition to observing their RRSO decision-making consultations in the clinic. The decision-making considerations among the carriers were centered around the overarching theme of "Negotiating cancer risk and womanhood priorities," with the following themes: (1) risk perception, (2) self-preservation, (3) motherhood obligation, and (4) the preciousness of marriage. Cognitive knowledge of BRCA risk was often conceptualized based on personal and family history of cancer, personal beliefs, and faith. Many women reported fears that RRSO would affect them physically and emotionally, worrying about the post-surgical impact on their motherhood responsibilities. Nevertheless, some reported feeling obliged to choose RRSO for the sake of their children. For some, their husband's support and approval were critical, with emotional well-being and sexuality reportedly perceived as important to sustaining married life. Despite reporting hesitancy toward RRSO, women's decisions about choosing this option evolved as their priorities changed at different stages of life. Recognizing during clinic encounters with Malaysian women that RRSO decision-making involves negotiating the likelihood of developing cancer with the societal priorities of being a woman, mother, and wife may serve to support their decision-making.

Do BRCA1/2 mutation carriers have an earlier onset of natural menopause?

It has been hypothesized that BRCA1/2 mutation carriers have an earlier age at natural menopause (ANM), although to date findings are inconclusive. This study assessed the influence of BRCA mutation status on ANM, and aimed to explore the reasons of inconsistency in the literature. Cross-sectional assessment from an ongoing nationwide cohort study among members of BRCA1/2 mutated families. Information was obtained by a standardized questionnaire. Kaplan-Meier curves were constructed, and Cox regression was used to assess the association between BRCA1/2 mutation status and ANM. Adjustments were made for birth cohort, family, smoking, use of hormonal contraceptives, and parity. A total of 1,208 BRCA1/2 mutation carriers and 2,211 proven noncarriers were included. Overall, no association was found between BRCA1/2 mutation status and ANM (adjusted hazard ratio [HR] = 1.06 [95% CI, 0.87-1.30]). We examined if the null finding was due to informative censoring by uptake of risk-reducing salpingo-oophorectomy. Indeed, within the oldest birth cohort, in which the percentage of surgical menopause events was lowest and comparable between carriers and noncarriers, the HR for earlier natural menopause in carriers was 1.45 (95% CI, 1.09-1.94). The second oldest birth cohort, however, demonstrated a decreased HR (0.67 [95% CI, 0.46-0.98]), and thus no trend over birth cohorts was found. Various types of selection bias hamper the comparison of ANM between BRCA1/2 mutation carriers and noncarriers, genetically tested in the clinic.

Differences in Uptake of Risk Reduction Strategies Among Underserved Populations

Differences in Uptake of Risk Reduction Strategies Among Underserved Populations

Uptake of risk-reducing salpingo-oophorectomy among female BRCA mutation carriers: experience at the National Cancer Center of Korea.

The aim of this study was to identify the uptake rate of risk-reducing salpingo-oophorectomy (RRSO) and the factors affecting this rate among female BRCA1 or BRCA2 mutation carriers at the National Cancer Center of Korea. Between April 2007 and December 2014, 450 women underwent BRCA gene testing, and 97 women were found to have BRCA1/2 mutations. Through the review of medical records, 42 candidates for RRSO were identified. Of these, 22 underwent RRSO. Demographic, clinical, and consultation-related factors were compared between the RRSO and non-RRSO groups. The uptake rate of RRSO was 52.4 %. The mean time interval between genetic testing and surgery in the RRSO group was 7.3 months (range 0.6-33.9). The prevalence of amenorrhea was greater in the RRSO group than in the non-RRSO group (59.1 % vs. 20.0 %; P = 0.010). More women in the RRSO group were consulted with gynecologic oncologists (95.5 % vs. 60.0 %; P = 0.008). In multivariate analyses, amenorrhea at the time of genetic counseling (OR 16.44; 95 % CI 1.16-232.82; P = 0.038) and consultation with gynecologic oncologists (OR 30.78; 95 % CI 1.34-707.21; P = 0.032) were identified as factors affecting the carrier's decision to undergo RRSO. One patient in the non-RRSO group (5.0 %) developed primary peritoneal carcinoma, which was diagnosed 4.6 years after genetic testing. The uptake rate of RRSO among BRCA1/2 mutation carriers was affected by the presence of amenorrhea and consultation with gynecologic oncologists. Gynecologic oncologists with clinical experience with ovarian cancer should play a major role in aiding carriers' decision-making concerning RRSO.

The effect of personal medical history and family history of cancer on the uptake of risk-reducing salpingo-oophorectomy.

Women with an increased lifetime risk of ovarian cancer are advised to undergo risk-reducing salpingo-oophorectomy (RRSO) to reduce risk of adnexal cancer. We investigated the uptake of RRSO and evaluated the influence of personal medical history of (breast) cancer, risk-reducing mastectomy (RRM) and family history of ovarian and/or breast cancer on the RRSO decision. This single center retrospective observational cohort study was performed in a tertiary multidisciplinary clinic for hereditary cancer of the University Medical Centre Utrecht, the Netherlands. Women ≥35 years old with an estimated lifetime risk of ovarian cancer ≥10 %, who had completed childbearing, were eligible for RRSO. Uptake and timing of RRSO were analyzed. Influence of personal medical history and family history on RRSO decision making, were evaluated with logistic regression. The study population consisted of 218 women (45.0 % BRCA1 mutation carrier, 28.0 % BRCA2 mutation carrier, 27.0 % with familial susceptibility) with 87.2 % RRSO uptake. The median age at RRSO was 44.5 (range 28–73) years. Of the women undergoing RRSO, 78.3 % needed ≤3 consultations to reach this decision. Multivariable analysis showed a significant difference in RRSO uptake for women with a history of RRM [OR 3.66 95 % CI (1.12–11.98)], but no significant difference in women with a history of breast cancer [OR 1.38 95 % CI (0.50–3.79)], nor with a family history of ovarian and/or breast cancer [OR 1.10 95 % CI (0.44–2.76)]. We conclude that RRSO counseling, without the alternative of screening, is effective. The uptake is increased in women with a history of RRM.

Stopping ovarian cancer screening in BRCA1/2 mutation carriers: Effects on risk management decisions & outcome of risk-reducing salpingo-oophorectomy specimens

ObjectiveOvarian cancer screening (OCS) for BRCA1/2 mutation carriers was stopped in our family cancer clinic in 2009 because of its ineffectiveness. The study objective was to investigate the effect of stopping OCS on the timing and uptake of risk-reducing salpingo-oophorectomy (RRSO) and on the percentage of occult cancers in the specimens. Methods419 BRCA1/2 mutation carriers were recruited between January 1999 and June 2013.Uptake, timing and the outcome of the RRSO specimens before stopping OCS (period I) were compared to those after stopping OCS (period II). ResultsThe percentage of women undergoing RRSO within the recommended age range increased from 81% to 95%. Receiving DNA test results in period II independently predicted a shorter time interval to RRSO (hazard ratio: 2.48, 95% confidence interval: 1.81–3.39). The incidence of detecting occult cancers in RRSO specimens before and after stopping OCS was 1.3% and 1.8%, respectively, and was not statistically significantly different. ConclusionsThe presentation of risk management options to women may influence their decision. The increased patient awareness of the ineffectiveness of OCS could have led to a higher percentage of women undergoing RRSO and doing so more often within the recommended age range.

Use of risk-reducing surgeries in a prospective cohort of 1,499 BRCA1 and BRCA2 mutation carriers.

Inherited mutations in BRCA1 or BRCA2 (BRCA1/2) confer very high risk of breast and ovarian cancers. Genetic testing and counseling can reduce risk and death from these cancers if appropriate preventive strategies are applied, including risk-reducing salpingo-oophorectomy (RRSO) or risk-reducing mastectomy (RRM). However, some women who might benefit from these interventions do not take full advantage of them. We evaluated RRSO and RRM use in a prospective cohort of 1,499 women with inherited BRCA1/2 mutations from 20 centers who enrolled in the study without prior cancer or RRSO or RRM and were followed forward for the occurrence of these events. We estimated the age-specific usage of RRSO/RRM in this cohort using Kaplan-Meier analyses. Use of RRSO was 45% for BRCA1 and 34% for BRCA2 by age 40, and 86% for BRCA1 and 71% for BRCA2 by age 50. RRM usage was estimated to be 46% by age 70 in both BRCA1 and BRCA2 carriers. BRCA1 mutation carriers underwent RRSO more frequently than BRCA2 mutation carriers overall, but the uptake of RRSO in BRCA2 was similar after mutation testing and in women born since 1960. RRM uptake was similar for both BRCA1 and BRCA2. Childbearing influenced the use of RRSO and RRM in both BRCA1 and BRCA2. Uptake of RRSO is high, but some women are still diagnosed with ovarian cancer before undergoing RRSO. This suggests that research is needed to understand the optimal timing of RRSO to maximize risk reduction and limit potential adverse consequences of RRSO.

Risk Management Options Elected by Women After Testing Positive for a BRCA Mutation

Women who carry BRCA germ line mutations are at high risk for breast and ovarian cancer. The National Comprehensive Cancer Network (NCCN) and other national groups have established guidelines for identification of women at risk for carrying these mutations, referral of these women for genetic testing, and use of risk-reducing strategies for management of those who test positive. Recommended strategies include risk-reducing salpingo-oophorectomy (RRSO) by age of 35 to 40 years; risk-reducing mastectomy (RRM); and surveillance at defined intervals using pelvic ultrasound, CA 125, mammogram, and breast magnetic resonance imaging (MRI). Despite the proven effectiveness of these strategies in reducing risk, their uptake varies greatly. The aim of this retrospective cohort study was to assess the uptake of these risk management options among women at risk for ovarian and breast cancer who tested positive for BRCA mutations at Kaiser Permanente Northern California, a community-based integrated health system. Management of a cohort of deleterious BRCA mutation carriers (1995–2012) in a community setting was evaluated for consistency with NCCN guidelines. The use of chemoprevention and hormone replacement was also evaluated. Women who tested positive for a mutation were followed at each 12-month interval for 5 years. Of the 305 eligible women, 170 (56%) were BRCA1 positive, and 135 (44%) were BRCA2 positive. Seventy-four percent of the women testing positive underwent RRSO (only 17% were aged < 40 years), whereas 44% underwent RRM. Median time from testing to both RRSO and RRM was 6 months. The first year after diagnosis, 45% of the women underwent a pelvic ultrasound, dropping to 2.3% by year 5. Similarly in year 1, a total of 47% had at least 1 CA 125, dropping to 2% by year 5. There was a similar drop off from years 1 to 5 among the women undergoing annual MRI and mammogram (from 35% to 3% for MRI and 43% to 7% for mammogram). The frequency of oral contraceptive use was also low (16%); only 1 woman used tamoxifen as chemoprevention for breast cancer. These findings show that uptake of RRSO in BRCA carriers in a community-based US health system was high, but few were younger than 40 years at the time of surgery. Compliance with NCCN-recommended guidelines for surveillance was low even at 1 year after testing and rapidly declined after the first year. The data show the need for an integrated system for early identification of carriers and improved risk reduction by use of standardized management strategies that improve compliance.

Oncology health professionals' attitudes toward treatment-focused genetic testing for women newly diagnosed with breast cancer.

This study explored the attitudes of oncology health professionals towards treatment-focused genetic testing (TFGT) for women newly diagnosed with breast cancer. Members of several relevant medical organizations in Australia and New Zealand were invited via email to participate in an online survey. A total of 149 respondents, including 40 surgeons, 46 oncologists and 63 breast care nurses, completed the online questionnaire. The majority of respondents believed that TFGT was useful for patient care (87.3%) and valuable for the treatment and management of breast cancer (90.6%). In multivariable analyses, breast care nurses were significantly more likely to agree that TFGT was useful for patient care and the treatment and management of breast cancer compared with oncologists and surgeons (β = 0.30; 95% CI: 0.01-0.60; p = 0.045). Participants also agreed that TFGT has an impact on treatment decision-making (96.0%), uptake of bilateral mastectomy (98.7%) and uptake of risk-reducing salpingo-oophorectomy (98.0%) in women newly diagnosed with breast cancer. A slight preference towards surgeons (49.7%) as the best health professional to make the initial offer of TFGT was observed and the majority of respondents suggested the best time to offer TFGT was shortly after diagnosis, when the treatment plan is discussed. The findings suggest health professionals have positive attitudes towards TFGT. Future training programs focusing on teamwork models and guidelines specifying health professionals' roles in regards to TFGT and follow-up management may be of benefit.

Psychosocial factors and uptake of risk-reducing salpingo-oophorectomy in women at high risk for ovarian cancer

Bilateral risk-reducing salpingo-oophorectomy (RRSO) has been shown to significantly reduce the risk of ovarian cancer. This study assessed factors predicting uptake of RRSO. Women participating in a large multiple-case breast cancer family cohort study who were at increased risk for ovarian and fallopian tube cancer (i.e. BRCA1 or BRCA2 mutation carrier or family history including at least one first- or second-degree relative with ovarian or fallopian tube cancer), with no personal history of cancer and with at least one ovary in situ at cohort enrolment, were eligible for this study. Women who knew they did not carry the BRCA1 or BRCA2 mutation segregating in their family (true negatives) were excluded. Sociodemographic, biological and psychosocial factors, including cancer-specific anxiety, perceived ovarian cancer risk, optimism and social support, were assessed using self-administered questionnaires and interviews at cohort enrolment. RRSO uptake was self-reported every three years during systematic follow-up. Of 2,859 women, 571 were eligible. Mean age was 43.3 years; 62 women (10.9 %) had RRSO a median of two years after cohort entry. Factors predicting RRSO were: being parous (OR 3.3, p = 0.015); knowing one's mutation positive status (OR 2.9, p < 0.001) and having a mother and/or sister who died from ovarian cancer (OR 2.5, p = 0.013). Psychological variables measured at cohort entry were not associated with RRSO. These results suggest that women at high risk for ovarian cancer make decisions about RRSO based on risk and individual socio-demographic characteristics, rather than in response to psychological factors such as anxiety.

Uptake of risk-reducing salpingo-oophorectomy in women carrying a BRCA1 or BRCA2 mutation: evidence for lower uptake in women affected by breast cancer and older women

Background:Bilateral risk-reducing salpingo-oophorectomy (BRRSO) is the only effective way of reducing mortality from ovarian cancer. This study investigates uptake of BRRSO in 700 BRCA1/2 mutation carriers from Greater Manchester.Methods:Dates of last follow-up and BRRSO were obtained, and the following variables were investigated: ovarian cancer risk/gene, age and breast cancer history. The date of the genetic mutation report was the initiation for Kaplan–Meier analysis.Results:The uptake of BRRSO in BRCA1 mutation carriers was 54.5% (standard error 3.6%) at 5 years post testing compared with 45.5% (standard error 3.2%) in BRCA2 mutation carriers (P=0.045). The 40–59 years category showed the greatest uptake for BRRSO and uptake was significantly lower in the over 60 s (P<0.0001). Of the unaffected BRCA1 mutation carriers, 65% (standard error 5.1%) opted for surgery at 5 years post-testing compared with 41.1% (standard error 5.1%) in affected BRCA1 mutation carriers (P=0.045).Conclusion:The uptake of BRRSO is lower in women previously affected by breast cancer and in older women. As there is no efficient method for early detection of ovarian cancer, uptake should ideally be greater. Counselling should be offered to ensure BRCA1/2 mutation carriers make an informed decision about managing their ovarian cancer risk.

Time to prophylactic surgery in BRCA1/2 carriers depends on psychological and other characteristics

PurposeTo investigate the medical and psychosocial factors determining the time to prophylactic surgery of unaffected women carriers of a deleterious BRCA1/2 mutation. MethodsProspective study on a French national cohort of unaffected BRCA1/2 carriers (N = 244); multivariate Cox proportional hazard modeling. ResultsMedian follow-up time was 2.33 years (range, 0.04–6.84 years). Time to surgery was shorter when the psychological impact of BRCA1/2 result disclosure was stated to be higher (P ≤ 0.01). Those who intended to opt for prophylactic surgery before being tested did so faster and more frequently after test disclosure than those who were undecided/opposed. The older the women were, the faster their uptake of risk-reducing salpingo-oophorectomy (adjusted hazard ratio >2.95; P < 0.001) was; the uptake of those with at least two children was also faster (adjusted hazard ratio = 2.51; [1.38–4.55]). Those who opted most quickly for risk-reducing mastectomy more frequently had a younger child at the time of testing (adjusted hazard ratio = 4.63 [1.56–13.74]). Time to surgery was shorter when there was a first-degree relative with ovarian/breast cancer (P ≤ 0.01). ConclusionTime to prophylactic surgery depends on the stated psychological impact of disclosure and on women's cognitive anticipation of surgery after adjusting on sociodemographic characteristics.

New Strategies in Ovarian Cancer: Uptake and Experience of Women at High Risk of Ovarian Cancer Who Are Considering Risk-Reducing Salpingo-Oophorectomy

Here, we review factors associated with uptake of risk-reducing salpingo-oophorectomy by women at increased hereditary risk for ovarian cancer, as well as quality of life issues following surgery. Forty-one research studies identified through PubMed and PsychInfo met inclusion criteria. Older age, having had children, a family history of ovarian cancer, a personal history of breast cancer, prophylactic mastectomy, and BRCA1/2 mutation carrier status increase the likelihood of undergoing surgery. Psychosocial variables predictive of surgery uptake include greater perceived risk of ovarian cancer and cancer-related anxiety. Most women report satisfaction with their decision to undergo surgery and both lower perceived ovarian cancer risk and less cancer-related anxiety as benefits. Hormonal deprivation is the main disadvantage reported, particularly by premenopausal women who are not on hormonal replacement therapy (HRT). The evidence is mixed about satisfaction with the level of information provided prior to surgery, although generally, women report receiving insufficient information about the pros and cons of HRT. These findings indicate that when designing decision aids, demographic, medical history, and psychosocial variables need to be addressed in order to facilitate quality decision making.

Association of personal and family history with decision to undergo risk-reducing salpingo-oophorectomy in BRCA mutation carriers

9560 Background: BRCA mutations carriers are at substantially increased risk to develop both breast and ovarian cancer. Current risk-reduction recommendations include consideration of risk-reducing salpingo-oophorectomy (RRSO) once childbearing is complete. Despite evidence supporting the efficacy of this approach, many patients do not pursue this option. In order to further evaluate this issue, we examined predictors of RRSO uptake in a large cohort of prospectively ascertained BRCA mutation carriers. Methods: Medical records of all women with a BRCA1 or BRCA2 mutation identified between 6/1995 and 12/2003 with ovarian tissue at risk and enrolled on one of two prospective follow-up studies were evaluated. Univariate analysis of demographic variables hypothesized to be predictive of RRSO uptake was performed. Variables significant in univariate analysis were analyzed in a multivariate logistic regression model. Results: Of 339 women meeting the study criteria, 213 (62.8%) elected to undergo RRSO after receiving genetic testing results. On univariate analysis, age ≥ 40 (Odds Ratio (OR) 5.99, 95% CI [3.67, 9.78]}, personal history of breast cancer (OR 2.09, [1.33, 3.27]), parity (OR 2.43, [1.49, 3.94]) and post-menopausal status (OR 3.11, [1.89, 5.13]) were predictive of uptake of RRSO. Family history of breast (OR 0.72, [0.46, 1.13]) or ovarian cancer (OR 1.60, [0.87, 3.00]) in a 1st degree relative was not predictive of RRSO uptake. On multivariate analysis, only age ≥ 40 (OR 4.92, [2.69, 9.00]) or history of a live birth (OR 2.25, [1.29, 3.90]) were predictive of uptake of RRSO. Conclusions: The decision to undergo RRSO in BRCA mutation carriers was not significantly impacted by personal history of breast cancer or family history of breast or ovarian cancer. Thus, other factors most likely play a central role. Given the high uptake of RRSO in this series, it appears that risk notification based in genetic counseling is highly effective in influencing preventive behaviors, independently of all other factors except age and parity. No significant financial relationships to disclose.