Prophylactic Bilateral Salpingo-oophorectomy Research Articles

Fear of cancer recurrence in breast cancer survivors carrying a BRCA1/2 mutation: A qualitative study.

There is preliminary evidence suggesting that FCR is a major problem for breast cancer survivors carrying a BRCA1/2 mutation. The goal of this qualitative study, conducted among women who were treated for breast cancer, was to provide a deeper understanding of how FCR is experienced in the context of a genetic predisposition to breast cancer. Three focus groups (90-110 min) were conducted with 19 breast cancer survivors carrying a BRCA1/2 mutation. The semistructured interview probed FCR level and impact, the role FCR played in the decision to have a prophylactic bilateral mastectomy and/or salpingo-oophorectomy, the effect that surgery had on FCR, and the relevance of offering a psychological intervention targeting FCR to this population. Findings indicated that FCR was a significant issue in these women, even though a majority had undergone a prophylactic surgery. Patients strongly affirmed the need to develop and provide access to FCR interventions that are specifically adapted to the needs of this group. These results suggest that, although being the most effective medical option to reduce the actual risk of local recurrence (or second breast cancer), prophylactic surgery only partially reduces FCR. A psychological intervention targeting specifically FCR would be an appropriate complement to preventive surgery.

Pathogenic germline variants in patients with breast cancer: conversations across generations, practices and patients' attitude.

Background: Breast cancer susceptibility genes such as BRCA1, BRCA2, PALB2, CHEK2 and many others are increasingly recognized among our patient population. In addition to their impact on treatment decisions of tested patients themselves, identifying at-risk family members offer opportunities for cancer preventive measures. Methods: This is an observational cross-sectional study of adult breast cancer patients with positive breast-cancer-susceptibility germline variants who received treatment at our institution. Patients with variants of uncertain significance (VUS), or who refused to give consent, were excluded. The data was collected from an eligible sample of breast cancer patients using a structured questionnaire developed by the study team and tested for validity and reliability, as well as a clinical chart review form. Patients were invited to participate in the study during their scheduled oncology clinics visit. Results: 169 patients were enrolled, including 42 (24.9%) with pathogenic/likely pathogenic (P/LP) BRCA1 variants, 84 (49.7%) with BRCA2 and 43 (25.4%) with non-BRCA variants. All patients were female and the mean age was 45 ± 9.9years. Among 140 eligible patients, 104 (74.3%) underwent prophylactic mastectomy, while 79 (59.0%) of 134 eligible patients had prophylactic bilateral salpingo-oophorectomy (BSO). Results were communicated with family members by majority (n = 160, 94.7%), including 642 first degree female relatives, and 286 (44.5%) of them have taken no action. Fear of positive test results, cost of testing, unwillingness to undergo preventive measures, and social stigma were cited as barriers to genetic testing in 54%, 50%, 34% and 15%, respectively. Conclusion: Risk-reducing interventions including mastectomy and BSO were carried by majority of patients with P/LP variants. However, though the rate of communication of genetic testing results with family members was high, proper preventive measures were relatively low. Cost and fear of cancer diagnosis, were the leading causes that prevented cascade testing in our cohort.

An exploration of body image distress in women who underwent a prophylactic bilateral salpingo-oophorectomy (PBSO)

An exploration of body image distress in women who underwent a prophylactic bilateral salpingo-oophorectomy (PBSO)

Decision-analytic evaluation of the comparative effectiveness and cost-effectiveness of strategies to prevent breast and ovarian cancer in German women with BRCA-1/2 mutations

BackgroundWomen with inherited mutations in the BRCA1 or BRCA2 genes have increased lifetime risks for developing breast and/or ovarian cancer and may develop these cancers around the age of 30 years. Therefore, prevention of breast and ovarian cancer in these women may need to start relatively early in life. In this study we systematically evaluate the long-term effectiveness and cost effectiveness of different prevention strategies for breast and ovarian cancer in women with BRCA-1/2 mutation in Germany.MethodsA decision-analytic Markov model simulating lifetime breast and ovarian cancer development in BRCA-1/2 carriers was developed. Different strategies including intensified surveillance (IS), prophylactic bilateral mastectomy (PBM), and prophylactic bilateral salpingo-oophorectomy (PBSO) alone or in combination at different ages were evaluated. German clinical, epidemiological, and economic (in 2022 Euro) data were used. Outcomes included cancer incidences, mortality, life years (LYs), quality-adjusted life years (QALYs), and discounted incremental cost-effectiveness ratios (ICER). We adopted the German health-care system perspective and discounted costs and health effects with 3% annually.ResultsAll intervention strategies are more effective and less costly than IS alone. Prevention with PBM plus PBSO at age 30 maximizes life expectancy with 6.3 LYs gained, whereas PBM at age 30 with delayed PBSO at age 35 improves quality of life with 11.1 QALYs gained, when compared to IS alone. A further delay of PBSO was associated with lower effectiveness. Both strategies are cost effective with ICERs significantly below 10,000 EUR/LYG or QALY.ConclusionBased on our results, PBM at age 30 plus PBSO between age 30 and 40 prolongs life and is cost effective in women with BRCA-1/2 mutations in Germany. Serial preventive surgeries with delayed PBSO potentially improve quality of life for women. However, delaying PBM and/or PBSO further may lead to increased mortality and reduced QALYs.

Barriers to hormone therapy following prophylactic bilateral salpingo-oophorectomy in BRCA1/2 mutation carriers.

This study aimed to identify barriers to hormone therapy (HT) use among women with BRCA1/2 mutations after prophylactic bilateral salpingo-oophorectomy (BSO). A cross-sectional, electronic survey was conducted of BRCA1/2 mutation carriers at Women and Infants Hospital, Yale Medical Center, Hartford Healthcare, and Maine Medical Center. This study was a subanalysis of a subset of female BRCA1/2 mutation carriers who had undergone a prophylactic BSO. Data were analyzed using the Fisher's exact test or t test. We performed a subanalysis of 60 BRCA mutation carriers who underwent a prophylactic BSO. Only 24 women (40%) reported ever using HT. HT use was higher in women who underwent their prophylactic BSO at age younger than 45 years (51% vs. 25%, P = 0.06). Among all women who had a prophylactic BSO, the majority (73%) reported that a provider talked to them about using HT. Two thirds reported having seen contradictory information in the media about long-term consequences of HT. Seventy percent listed their provider as the primary influence in their decision to start HT. The most common reasons for not starting HT included it not being recommended by their physician (46%) and that it was not necessary (37%). BRCA mutation carriers frequently undergo prophylactic BSO at young ages, and less than half report using HT. This study highlights barriers to HT use, such as patient fears and physician discouragement, and identifies potential areas to improve educational efforts.

Does concomitant hysterectomy impact menopausal symptoms in premenopausal BRCA1/2 pathogenic carriers undergoing risk reducing salpingo-oophorectomy?

Prevention of high-grade serous carcinoma in women with a pathogenic variant in the BRCA1/2 genes includes prophylactic bilateral salpingo-oophorectomy (PBSO). There is debate on whether concomitant hysterectomy should be offered, with benefits including decreased risk of endometrial carcinoma and the option to use estrogen-alone menopausal hormone therapy (MHT), which is thought to be associated with better menopause-specific quality of life and lower breast cancer risk. The objective is to determine if BRCA1/2 mutation carriers undergoing premenopausal PBSO with concomitant hysterectomy have improved MENQOL compared with those women with an intact uterus.

INNV-05. CO-OCCURRENCES OF A HIGH-GRADE GLIOMA WITH CAVERNOUS MALFORMATIONS AND PATHOGENIC VARIANTS IN PDCD10 AND SMARCA4

Abstract INTRODUCTION The co-occurrence of multiple disease processes can make for more challenging diagnoses. Here we report an unusual case of a patient found to have an IDH1-mutant high-grade glioma along with multiple cerebral cavernous malformations and pathogenic germline variants in PDCD10 and SMARCA4. Case Description: A 17-year-old female presented with left arm paresthesia and weakness along with persistent headaches within the frontal and occipital regions that progressed in intensity to include nausea and emesis. A fast sequence magnetic resonance imaging (MRI) of her head was obtained that revealed the presence of multiple bilateral cystic lesions suspicious for cavernomas with the most notable lesion in the right parietal lobe. Ophthalmology consultation revealed grade III papilledema bilaterally. A full brain MRI with and without contrast was obtained and demonstrated a right anterior parietal lobe lesion with associated mass effect, as well as multiple bilateral supratentorial and left cerebellar cavernous malformations. The patient underwent tumor debulking of her dominant lesion. Pathology revealed an IDH1 mutant diffuse astrocytoma, WHO grade 3. Germline genetic testing was pursued which revealed a PDCD10 pathogenic variant consistent with familial cerebral cavernous malformation syndrome and a likely pathogenic variant in SMARCA4. Treatment of her high-grade-glioma included radiation therapy followed by maintenance oral temozolomide. DISCUSSION This case illustrates the unusual co-occurrences of a high-grade glioma with familial cavernous malformation syndrome and germline pathogenic variants in PDCD10 and SMARCA4. Our patient continues to do well clinically, but because of her now significant risk of developing ovarian cancer she has elected to undergo a prophylactic bilateral salpingo-oophorectomy. Recognition of abnormal genetic results is critical in the setting of multiple disease processes and can play a crucial role in the on-going care for a patient.

Hormone replacement therapy counseling at prophylactic bilateral salpingo-oophorectomy in high-risk patients (354)

<b>Objectives:</b> Women at high risk for ovarian cancer are advised to undergo bilateral salpingo-oophorectomy (RRSO) prior to natural menopause. Hormone replacement therapy (HRT) mitigates the negative effects of surgical menopause. We sought to understand how high-risk women are counseled about HRT and use patterns of HRT after RRSO. <b>Methods:</b> We performed a chart review of women seen at a high-risk clinic between 2000-2018 who underwent RRSO. Reviewing patient age, surgical details, pathology, documented HRT counseling, and whether HRT was recommended. We then surveyed by mail, online, and by phone all women alive and meeting study criteria (no surgery for ovarian malignancy, surgery not just for ovarian suppression for breast cancer) to determine what they recalled regarding counseling, use of HRT, cancer diagnoses, and depression (PHQ9), anxiety (GAD7), and cancer worry (CWS) scores. Chi-square test and t-test compared categorical and continuous variables, respectively. Logistic regression examined associations between age, history of cancer, surgeries, and reports of HRT discussions and recommendations. <b>Results:</b> A total of 150 women met the survey criteria, with a 60.1% response rate. The median age at the survey was 57.5 years (range: 37-86). RRSO median age was 46 (range: 27-74). Those surveyed included 76 <i>BRCA',</i> 50 <i>BRCA2,</i> 3 <i>BRCA1</i> and <i>BRCA2</i> mutation carriers, and 22 participants with other mutations or strong family histories. Responders and non-responders were alike in RRSO age and mutation status. About 44.4% of respondents recalled discussion about HRT; eight reported recommendations for HRT, 21 against, and 11 other guidance. Among the respondents, 51.5% reported undergoing hysterectomy; 17 (18.9%) respondents took HRT after surgery (64.7% estrogen alone). Five patients stopped HRT, three because a doctor advised, one because she was afraid, and one because she felt she no longer needed it. HRT recommendations were not associated with mastectomy (prophylactic or otherwise), hysterectomy, or cancer history. Younger age at RRSO was associated with receiving HRT counseling (RRSO age 43 if discussed vs 50 not discussed, p<0.01), but not with recommendations about HRT (RRSO age 41 if recommended vs 44 not recommended, p=0.06). RRSO age remained significant in predicting discussion, though other surgeries and cancer history did not. Starting or continuing HRT after RRSO was not indicative of depression or anxiety scores, but those taking HRT after RRSO had higher CWS (CWS > 10 in 82.4% with HRT vs 52.9% without, p=0.03). Eighteen (43.9%) respondents did not remember receiving counseling documented in the chart, while 15 (37.5%) remembered counseling that was not documented. <b>Conclusions:</b> A majority of patients undergoing RRSO did not receive HRT counseling, and nearly 44% did not remember documented HRT counseling. Surgeries and diagnoses that would impact HRT use were not correlated with recommendations. Younger age was correlated with discussion but not a recommendation for HRT. Before RRSO, we propose discussing HRT regardless of the recommendation for or against the use and providing written summaries to which patients and future healthcare providers can refer.

Influence of germline test results on surgical decision making in women with invasive breast cancer

BackgroundWhile therapeutic mastectomy with contralateral prophylactic mastectomy (TM+CPM) and/or bilateral salpingo-oophorectomy (BSO) are recommended for women with pathogenic variants (PV) in some cancer predisposition genes, evidence for the utility of these surgeries for women with PV in other genes currently is insufficient. In conjunction, current guidelines recommend that clinical management should not be influenced by a return of a variant of uncertain significance (VUS). Return of germline test results may, however, influence surgical decision making regardless of current guidelines. We thus evaluated surgical choices amongst a cohort of women with invasive breast cancer who underwent clinical genetic testing. MethodsGermline test results and all surgical procedures were extracted for women who had unilateral invasive breast cancer and had clinical testing before definitive surgery (n = 591). Results were classified as pathogenic/likely pathogenic (PV, 17.1%), VUS (19.5%) or benign/likely benign (63.4%). Data were analyzed using chi-square tests with p<0.05 defining significance. ResultsRates of TM+CPM and BSO were not significantly different for women with VUS compared to those with benign findings. Rates of TM+CPM were significantly higher for women with PV in BRCA1 and BRCA2, PALB2, PTEN and TP53, as well in genes with insufficient data to recommend risk-reducing mastectomy. Rates of BSO were significantly higher in women with PV in BRCA1 and BRCA2, PALB2, PTEN and TP53 and BRIP1, RAD51C and RAD51D compared to those with benign findings. ConclusionOverall, surgical choices for women with a VUS were more similar to those from women with benign variants than to those with PV, however, in the group with PV in genes for which insufficient evidence exists for the benefit of risk-reducing mastectomy, rates of TM+CPM were high. Thus, while the management of women with VUS is in agreement with ACMG guidelines, patients with mutations in other cancer genes demonstrate a preference for more aggressive breast surgeries.

HGG-19. Co-occurrences of a high-grade glioma with cavernous malformations and pathogenic variants inPDCD10 andSMARCA4

INTRODUCTION: The co-occurrence of multiple disease processes can make for more challenging diagnoses. Here we report an unusual case of a patient found to have an IDH1-mutant high-grade glioma along with multiple cerebral cavernous malformations and pathogenic germline variants in PDCD10 and SMARCA4. CASE DESCRIPTION: A 17-year-old female presented with left arm paresthesia and weakness along with persistent headaches within the frontal and occipital regions that progressed in intensity to include nausea and emesis. A fast sequence magnetic resonance imaging (MRI) of her head was obtained that revealed the presence of multiple bilateral cystic lesions suspicious for cavernomas, with the most notable lesion in the right parietal lobe. Ophthalmology consultation revealed grade III papilledema bilaterally. A full brain MRI with and without contrast was obtained and demonstrated a right anterior parietal lobe lesion with associated mass effect, as well as multiple bilateral supratentorial and left cerebellar cavernous malformations. The patient underwent tumor debulking of her dominant lesion. Pathology revealed an IDH1-mutant diffuse astrocytoma, WHO grade III. Tumor genetic testing was done and identified a SMARCA4 and two TP53 variants. Germline genetic testing was then pursued which revealed a PDCD10 pathogenic variant consistent with familial cerebral cavernous malformation syndrome and a likely pathogenic variant in SMARCA4. Treatment of her high-grade-glioma included radiation therapy followed by maintenance oral temozolomide. DISCUSSION: This case illustrates the unusual co-occurrences of a high-grade glioma with familial cavernous malformation syndrome and germline pathogenic variants in PDCD10 and SMARCA4. Our patient continues to do well clinically, but because of her risk of developing small cell carcinoma of the ovary she has elected to undergo a prophylactic bilateral salpingo-oophorectomy. Recognition of abnormal genetic results is critical in the setting of multiple disease processes and can play a crucial role in the on-going care for a patient.

Cancer Anxiety Mediates the Association Between Satisfaction With Medical Communication and Psychological Quality of Life After Prophylactic Bilateral Salpingo-Oophorectomy.

BackgroundProphylactic Bilateral Salpingo-Oophorectomy (PBSO) reduces the risk of developing ovarian cancer. However, the psychological mechanisms that may affect post-surgery Quality of Life (QoL) among patients who underwent PBSO are still largely unknown. Thus, this study aimed at exploring the direct and indirect associations of satisfaction with medical communication and cancer anxiety on post-surgery QoL among women at high risk of developing ovarian cancer.MethodFifty-nine women (mean age: 50.64 ± 6.7 years) who underwent PBSO took part in this cross-sectional study, filling out a sociodemographic and clinical questionnaire, a battery of validated psychological measures and an ad hoc developed scale for the assessment of cancer anxiety. We first examined the correlations among all variables of interest, and then tested if cancer anxiety mediated the association between satisfaction with medical communication and post-surgery psychological QoL, controlling both for time from surgery and education.ResultsPost-surgery psychological QoL was unrelated from any sociodemographic or clinical variable. Cancer anxiety had a significant direct negative effect on psychological QoL, while satisfaction with medical communication had a significant positive direct effect on it. Finally, cancer anxiety significantly mediated the association between satisfaction with medical communication and post-surgery psychological QoL.DiscussionResults suggest that post-surgery psychological QoL of patients who underwent PBSO may be increased with interventions, delivered in a genetic counselling setting, targeting quality of medical communication and cancer anxiety.

Abstract P2-10-02: Random periareolar fine-needle aspiration (RPFNA) cell number, prior precancerous breast disease and subsequent uptake of a prevention intervention predict short-term breast cancer risk

Abstract Introduction: In 2000 we published initial observations from a high-risk cohort of 480 women that cytologic evidence of hyperplasia with atypia in benign breast tissue obtained by random periareolar fine-needle aspiration (RPFNA) was associated with a five-fold increased risk of developing DCIS or invasive breast cancer at a median follow-up of 45 months [Fabian, JNCI 2000]. Few women in the initial cohort had any exposure to prevention agents, as NSABP-P1 was not reported until 1998. We began a new high-risk cohort in 2002 as the tissue processing changed from a filter technique to Thin PrepTM. The superior nuclear detail permitted assessment of cytologic atypia in the absence of high cellularity. Women in the second cohort were told that RPFNA atypia was a risk factor for developing breast cancer and in addition to standard prevention options were offered participation in clinical trials, if applicable. The purpose of this subsequent analysis was to determine if the predictive value of RPFNA atypia was maintained with change in tissue processing and availability of prevention options. Methods: A total of 1,135 high-risk women, eligible on the basis of family history, BRCA1/2 mutation status, prior biopsy indicating LCIS or atypical hyperplasia (AH), prior contralateral breast cancer and/or high mammographic breast density, underwent baseline RPFNA and were enrolled in our second cohort between 2002 and 2015. As in the earlier study published in 2000, if women had 2 aspirations without an intervening intervention within 21 months the worse result was utilized as baseline. In addition to cytomorphology, breast tissue was also categorized by cellularity of the aspirate (10-100, 100-1000, 1000-5000, and &amp;gt;5000 cells per cytology slide). The primary aspirator (CJF) and cytopathologist (CMZ) were the same for both cohorts. Women were censored at the time of prophylactic mastectomy, development of other site cancer, or death. Kaplan-Meier hazard plots and Cox-regression analysis were used to analyze time to development of DCIS or invasive breast cancer and effect of joint variables, respectively. Results: At a median follow-up of 86 months, 79 cases of DCIS or invasive breast cancer had been diagnosed. By univariate analysis, RPFNA atypia at entry was not predictive of subsequent breast cancer (p=0.58; log-rank test). However, breast cancer risk was increased by a prior breast biopsy with LCIS or AH (HR 2.6, 95% CI 1.6-2.4, p&amp;lt;0.001) or by high RPFNA cellularity, defined as &amp;gt;5000 epithelial cells per RPFNA cytomorphology slide (HR 2.1, 95% CI 1.3-3.5, p=0.0034). Thirty-six percent of women subsequently chose to undergo a prevention intervention, including a standard drug, enrollment in a prevention clinical trial of 6-12 months duration, or a prophylactic bilateral salpingo-oophorectomy (BSO) prior to age 45. Prevention interventions were more prevalent in women with RPFNA atypia (49% vs 30%, p&amp;lt;0.001). Not only was uptake of a prevention intervention associated with reduced breast cancer risk on univariate analysis (p=0.043), it was retained on multivariate analysis. The final Cox Regression risk model included prior breast biopsy with LCIS or AH (HR 2.4, 95% CI 1.5-3.9; p&amp;lt;0.001), high RPFNA cellularity (HR 2.2, 95% CI 1.3-3.7; p=0.003) and prevention intervention (HR 0.54, 95% CI 0.33-0.89; p=0.015). Conclusions: In a second large cohort of high-risk women for whom RPFNA acquired cells were processed to slides via ThinPrep™, high RPFNA cellularity (&amp;gt;5000 epithelial cells/slide) but not cytologic atypia predicted short-term breast cancer risk. However, women with atypia were significantly more likely than women without atypia to participate in a prevention intervention, which in turn was associated with reduced breast cancer risk Citation Format: Whitney L Hensing, Carol J Fabian, Carola M Zalles, Priyanka Sharma, Amy L Kreutzjans, Kandy R Powers, Lynn Chollet-Hilton, Bruce F Kimler. Random periareolar fine-needle aspiration (RPFNA) cell number, prior precancerous breast disease and subsequent uptake of a prevention intervention predict short-term breast cancer risk [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P2-10-02.

Abstract P2-09-04: Timing and acceptance of bilateral prophylactic salpingo-oophorectomy among BRCA1 and BRCA2 mutation carriers enrolled in an integrated community-based health care system

Abstract BACKGROUND Risk reducing bilateral salpingo-oophorectomy (rrBSO) can provide up to a 90% reduction in the risk of developing ovarian cancer in women who are carriers of pathogenic variants in the BRCA1 and BRCA2 genes. National guidelines recommend risk reducing rrBSO once childbearing is complete and/or between the ages of 35-45. Previous studies have found that a large percentage of women who are eligible for rrBSO do not undergo the procedure and surgery is often done at later ages than recommended in the national guidelines. Research on factors associated with the uptake and timing of rrBSO is limited. Our study describes the percentages of women who are BRCA1 or BRCA2 carriers who elected rrBSO and ascertains the timing of the surgery relative to recommended age guidelines. We also identify patient characteristics associated with uptake of rrBSO. METHODS We conducted a retrospective cohort study in a large, integrated healthcare system in Southern California. The study population included women who were identified as BRCA1 or BRCA2 carriers in our electronic health record by ICD 9 and ICD 10 codes, and by review of our internal Cancer DNA database. Inclusion criteria included adults 18 years and older who were members of Kaiser Permanente Southern California between 2008 - 2018. Exclusion criteria included patients with an established diagnosis of ovarian cancer, with rrBSO at the time of study entry, and who were KP members for less than 12 months. Crude logistic regression models were used to determine odds ratios and 95% confidence intervals for associations between patient variables and uptake of rrBSO. RESULTS Of the 2,592 patients in the cohort, 1,326 were BRCA1 carriers and 1,266 were BRCA2 carriers. 1,003 (38.6%) women underwent rrBSO at a median age of 48.0 years (IQR: 42.0, 57.0). For the entire cohort, 38.6% identified as Caucasian, 30% identified as Hispanic/Latin American/Caribbean, 9.4% identified as Ashkenazi Jewish, 8.6% identified as Asian/Pacific Islander, and 1.5% identified as Black/African, and 1.4% identified as Near East/Middle Eastern. The baseline characteristics of our cohort can be seen in Table 1. Ovarian malignancy was incidentally detected on pathology evaluation in 1.5% of patients who elected rrBSO. The odds of rrBSO were lower among those who had used oral contraceptives for more than one year compared to those who hadn’t (OR=0.18, 95% CI: 0.11-0.30). A family history of ovarian cancer or breast cancer were also associated with higher odds of rrBSO, (OR=1.45, 95% CI: 1.21-1.73) and (OR=1.75; 95% CI: 1.48-2.08), respectively. The odds of rrBSO were also higher for those with a personal history of breast cancer (OR=2.29, 95% CI: 1.95-2.70). CONCLUSIONS In this large cohort of women who were BRCA1 and BRCA2 carriers and who were eligible for rrBSO, only a third of patients underwent risk reducing surgery. Among those who did undergo surgery, the median age at the time of procedure was higher than what is recommended in national guidelines. Family history of breast cancer and/or ovarian cancer, as well as personal history of breast cancer were associated with women selecting rrBSO. Table 1.No Oophorectomy (N=1589)rrBSO (N=1003)Total (N=2592)p valueAge at BRCA diagnosis&amp;lt;0.00011 N158910032592 Mean (SD)43.9 (15.73)49.5 (11.11)46.1 (14.38) Median42.048.345.5 Range(18.1-95.7)(19.8-79.7)(18.1-95.7)Gene0.03522 BRCA1839 (52.8%)487 (48.6%)1326 (51.2%) BRCA2750 (47.2%)516 (51.4%)1266 (48.8%)Race/Ethnicity0.01002 African72 (4.5%)61 (6.1%)133 (5.1%) Ashkenazi Jewish134 (8.4%)110 (11%)244 (9.4%) Asian/Pacific Islander138 (8.7%)86 (8.6%)224 (8.6%) Black24 (1.5%)14 (1.4%)38 (1.5%) Hispanic/Latin American/Caribbean486 (30.6%)291 (29%)777 (30%) Multiple2 (0.1%)2 (0.2%)4 (0.2%) Native American/Alaskan2 (0.1%)0 (0%)2 (0.1%) Near East/Mideast24 (1.5%)13 (1.3%)37 (1.4%) White/Caucasian (Western/Northern/Central European)611 (38.5%)389 (38.8%)1000 (38.6%) Other77 (4.8%)37 (3.7%)114 (4.4%) Unknown19 (1.2%)0 (0%)19 (0.7%)Oral contraceptive use ≥ 1 year&amp;lt;0.00012 N1456 (91.6%)987 (98.4%)2443 (94.3%) Y133 (8.4%)16 (1.6%)149 (5.7%)Family history of ovarian cancer0.00012 N1236 (77.8%)710 (70.8%)1946 (75.1%) Y353 (22.2%)293 (29.2%)646 (24.9%)Family history of breast cancer&amp;lt;0.00012 N650 (40.9%)284 (28.3%)934 (36%) Y939 (59.1%)719 (71.7%)1658 (64%)Personal history of breast cancer&amp;lt;0.00012 N1094 (68.8%)492 (49.1%)1586 (61.2%) Y495 (31.2%)511 (50.9%)1006 (38.8%)Age at prophylactic surgery NN/A893893 Mean (SD)49.6 (10.36)49.6 (10.36) Median48.048.0 Q1, Q342.0, 57.042.0, 57.0 Range(21.0-80.0)(21.0-80.0)Ovarian cancer&amp;lt;0.00012 N1589 (100%)988 (98.5%)2577 (99.4%) Y0 (0%)15 (1.5%)15 (0.6%)1Kruskal Wallis 2Chi-Square Citation Format: Karen W Kwan, Stephanie W Morton, Joanie Chung. Timing and acceptance of bilateral prophylactic salpingo-oophorectomy among BRCA1 and BRCA2 mutation carriers enrolled in an integrated community-based health care system [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P2-09-04.

Feasibility of Risk Reducing Salpingo-Oophorectomy at the Time of Abdominal Surgery for Correction of Pelvic Organ Prolapse and Urinary Incontinence.

Objective:The objective of this study is to assess the perioperative outcomes when prophylactic bilateral salpingo-oophorectomy (BSO) is performed concomitantly with surgery to repair pelvic organ prolapse (POP) or stress urinary incontinence (SUI).Materials and Methods:This is a retrospective case–control study of patients who underwent abdominal surgery for the correction of POP and/or SUI with or without concomitant BSO at a tertiary care center. The primary outcome measures were postsurgery length of hospitalization, estimated blood loss, and 30-day readmission rate. The secondary outcome measure was detection of ovarian cancer precursor lesions.Results:We identified 734 patients who had surgery for POP and/or SUI. The control group contained 385 patients, and the BSO group contained 349 patients. There was no difference between the control and BSO groups in the postsurgery length of stay (LOS) (35.2 h vs. 34.1 h; P = 0.49), and all-cause 30-day readmission rate (14.2% vs. 11.6%; P = 0.3085). However, there was decreased blood loss (40.8 ml vs. 67.2 ml, P < 0.0001) in the BSO group compared to the control group. Sub-analysis of primary outcomes in postmenopausal women (age > 55) showed decreased postsurgery LOS (33.4 h vs. 37.4 h; P = 0.0208) and decreased blood loss (35.9 ml vs. 82.7 ml; P < 0.0001) in the BSO group compared to control.Conclusion:Secondary to the lack of additional complications, we recommend surgeons give more consideration to finding appropriate candidates for a risk reducing BSO at time of abdominal surgery to repair POP or SUI.

Barriers to hormone replacement therapy following prophylactic bilateral salpingo-oophorectomy in BRCA1/2 mutation carriers

Barriers to hormone replacement therapy following prophylactic bilateral salpingo-oophorectomy in BRCA1/2 mutation carriers

Patient reported experiences following laparoscopic prophylactic bilateral salpingo-oophorectomy or salpingectomy in an ambulatory care hospital.

Women at risk of developing ovarian cancer because of a BRCA1 or BRCA2 pathogenic variant are candidates for prophylactic bilateral salpingo-oophorectomy (BSO). While BSO surgeries are routinely performed, to our knowledge there are no studies that have examined patient-reported experiences following laparoscopic BSO performed in an ambulatory care setting. The objective of this study was to examine whether women undergoing prophylactic laparoscopic BSO felt they were adequately informed about post-operative outcomes. A telephone interview was conducted among 46 women undergoing laparoscopic BSO to collect detailed information regarding surgical outcomes, complications, symptoms, and time to return to daily activities. The average age at surgery was 45.0years (range 34-66) and 67% of women underwent BSO prior to age 50. The mean reported hospital stay was 7.2h (range 4-12h) and at time of discharge, 78% of the women felt well enough to go home. None of the women required a readmission to hospital. Forty-three percent (n = 20) of the women did not feel well informed about what to expect post-operatively. Most of the patient-reported outcomes (including pain, vaginal bleeding, and nausea/vomiting) were expected and patient-reported menopausal symptoms were more common among women who were premenopausal at surgery. In terms of returning to regular activities, premenopausal women (n = 36) resumed sexual activity on average at 43days (range 2-365), which is later than postmenopausal women (n = 15) at 19days (range 7-30). On average, women returned to full-time work in 16days (range 1-56days). Despite patients receiving pre-surgery counselling, our findings suggest that there is a need to provide supplemental, reinforcing patient materials in preparing patients for what to expect after surgery.

Tumores ginecológicos en pacientes portadoras de mutación BRCA1 y BRCA2

ObjectiveTo analyse the incidence of breast and ovarian cancer, and the characteristics of these tumours, in patients with BRCA1-2 mutations. Patients and methodsRetrospective observational study that included a total of 111 patients with a molecular diagnosis of mutation in BRCA1 (56) and / or BRCA2 (55) genes. ResultsIn 69.4% of the cases, genetic testing was performed after oncological diagnosis. The incidence of breast and ovarian cancer was 62.2% and 20.7%, respectively. The most frequent histological type of breast cancer was infiltrating ductal (89.7%). A total of 67.7% of breast tumours in BRCA1 patients had a triple negative phenotype and 80% of BRCA2 patients showed a luminal phenotype. Most (87%) ovarian cancers were high grade serous carcinomas. In 41.4% of the patients, prophylactic mastectomy was performed, with a coincidental pathological finding in 19.5% of the surgical specimens. In 41.4% of the patients, prophylactic bilateral salpingo-oophorectomy was performed, with 6.5% of surgical specimens showing pathological lesions. ConclusionsThe incidence of breast/ovarian cancer in patients harbouring BRCA 1-2 mutations is higher than in the general population, and the cancer develops in younger patients. However, the genetic diagnosis of the mutation is usually secondary to that of the oncological event. The early diagnosis of the mutation based on family history should be emphasised in order to initiate early screening and risk-reduction measures.

Abstract P6-08-34: Genetic testing for hereditary breast cancer in Brazilian public health system: The experience of tumor board reference in a cancer center

Abstract Introduction: In Brazil, genetic testing for hereditary cancer predisposition syndromes, including Hereditary Breast Cancer (HBC), is not covered by the public health system (SUS) and was only incorporated in most private health insurance (PHI) plans after 2013. Nonetheless, considering that only 22% of the Brazilian population has access to private health system and the high cost of genetic testing in private laboratories, the majority of Brazilian women at risk for HBC do not have access to a genetic diagnosis. In this context, we have implemented at A.C.Camargo Cancer Center (ACCCC – a reference Cancer Center in Brazil which serves both the private and public health systems) a pilot program that offers genetic testing for SUS patients at risk for HBC. The goal of this study is to present the adopted clinical criteria and the corresponding detection rate of pathogenic variants in HBC genes observed in our cohort in comparison to detection rates observed in private health scenario. Methods: Since 2018, 34 cases of breast cancer patients from SUS under medical follow-up at ACCCC and at risk for HBC were discussed in multidisciplinary Tumor Board meetings. The Tumor Board team consists of health care professionals from different specialties, including medical oncologists, surgeons, pathologists, molecular biologists, and clinical geneticists. The clinical criteria defined for referring patients to genetic testing were: (1) personal history of triple negative breast cancer (TNBC) in any age; (2) personal history of non-TNBC developed before 30 years old, positive family history of cancer, and a PENN II model prediction of &amp;gt;15% risk in carry a BRCA1/2 mutation; and (3) personal history of BC in any age and a PENN II model prediction of &amp;gt;30% risk in carry a BRCA1/2 mutation. Detection rates of SUS patients were compared to BRCA1/2 results obtained during the same period from the ACCCC Laboratory of Genomics Diagnostics that serves manly PHI and private patients. Genetic tests were performed using different gene panels containing 26 or 94 genes. Results: Pathogenic (P) and likely pathogenic (LP) variants were detected in 38% of SUS patients (13/34), with a higher proportion of BRCA1 carriers (69% - 9 patients) than of BRCA2 (1 patient). Aside BRCA1/2 mutations that were detected in 10 patients (29%), P/LP variants were also identified in BRIP1, CHEK2, and PALB2 (1 patient each). The rate for BRCA1/2 P/LP variants in PHI cohort was 9.8% (23/234 patients), with a lower proportion of BRCA1 carriers (22%) than of BRCA2 (40%). It was identified a high rate of P/LP variants in TNBC from SUS cohort (62% - 10/16 cases) and a marked association of BRCA1 and TNBC, with 80% (8/10) of hereditary TNBC having BRCA1 mutations. The mean turnaround time for genetic test results was 4 months, varying from 2 to 8 months. From 11 patients with P/LP variants that already received the genetic test result, 5 underwent prophylactic contralateral mastectomy and/or bilateral salpingo-oophorectomy. Conclusions: The introduction of genetic testing for HBC made possible to tailor preventative measures for women at high risk, including prophylactic surgery and screening protocols. However, in many developing countries, the high cost of genetic tests and the lack of national policies prevent its application in clinical practice for the majority of the population. By defining more stringent clinical criteria for HBC genetic test, we detected a mutation rate three times as high as that detected in the private health scenario. With the continuity our study, we expect to contribute to the development of national standards for HBC screening and to encourage the implementation of consistent and cost-effective genetic testing under the real-life conditions of our public health system, maximizing the benefit for the population with the available resources. Citation Format: Dirce M Carraro, Giovana T Torrezan, Karina M Santiago, Maria\ Nirvana da Cruz Formiga, Solange M Sanches, Fabiana BA Makdissi, Breast Cancer Tumor Board Team. Genetic testing for hereditary breast cancer in Brazilian public health system: The experience of tumor board reference in a cancer center [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P6-08-34.

The incidence of occult ovarian neoplasia and cancer in BRCA1/2 mutation carriers after the bilateral prophylactic salpingo-oophorectomy (PBSO): A single-center prospective study

BackgroundDue to ineffective ovarian cancer (OC) screening programs, prophylactic bilateral salpingo-oophorectomy (PBSO) is suggested for BRCA1/2 genes mutation carriers. The reported incidence of clinically occult neoplasia and OC detected during PBSO varies widely (2–17 %), reflecting differences in studies design. ObjectiveWe aimed to prospectively evaluate the incidence of occult neoplasia in specimens collected during PBSO performed in a single tertiary center and to determine the effectiveness of this procedure in BRCA1/2 mutation carriers. Study designBetween January 2010 and October 2016 a total of 564 new germline BRCA1/2 mutation positive women were identified and 71 carriers underwent laparoscopic PBSO. Patients were prospectively followed-up after the surgery and data on operation, age, complications, histological reports and BRCA1/2 gene mutation types were collected and analyzed. ResultsSerous tubal intraepithelial carcinoma (STIC) was diagnosed in 7 (9.85 %) and OC in 4 (5.6 %) women (one advanced (FIGO IIIC) and 3 early (FIGO IA/C) stages); total incidence 15.5 %. Women's mean age at the time of surgery was 46.5 years. The mean age of women diagnosed with STIC and OC was 45.9 years (42–64). The mean follow up time for women being diagnosed with OC/STIC was 3.72 years; no recurrence was observed. The median time to perform laparoscopic PBSO was 43 min. (ranging from 25 to 65 min.), no surgical complications occurred during this operation. Interestingly, we found statistically significant (P = 0.0105) enrichment of STIC lesions in BRCA1 c.4035delA (an established Baltic founder mutation) carriers group. ConclusionThe incidence of pathological findings in BRCA1/2 mutation carries after PBSO is sufficiently high and our prospective study data supports PBSO as the most effective measure for reducing the risk of OC in BRCA1/2 mutation carriers. A novel finding of the enrichment of STIC lesions in BRCA1 c.4035delA carriers may show important biological differences in OC tumorigenesis between different BRCA1 mutations, which warrant further investigations.

Videolaparoscopic propylactic salpingo-oophorectomy: initial experience

Introduction: The BRCA mutation substantially increases the risk of ovarian cancer, from 20% to 60% when the mutation is in BRCA1, and 10% to 20% in BRCA1. Bilateral salpingo-oophorectomy may be the most important intervention in these patients, with clear impact on the reduction of mortality caused by ovarian cancer, and about 85% to 50% of reduction in the incidence of breast cancer. Salpingo-oophorectomy should be performed from the ages of 35 to 40 in patients with BRCA1 mutation, and after the age of 40 for BRCA2 carriers. Objectives: To present our initial experience of prophylactic bilateral salpingo-oophorectomy in patients with BRCA mutation. Method: This is a retrospective study. We included all patients who had tested positive for the BRCA mutation assisted from 1999 to 2019. Seven patients were identified with BRCA mutation and underwent videolaparoscopic salpingo-oophorectomy. The procedure was classic. The pieces were removed in endobags and sent to histological analysis with serial sections. The study was approved by the Research Ethics Committee, report n. 2.817.502. Results: No tumor was found in the surgical piece. The mean age of patients when they underwent surgery was 45.8 years. The patients, together, added 21 cases of breast cancer and 4 cases of ovarian cancer among 1st, 2nd and 3rd degree relatives. Five (71.4%) patients presented with BRCA1 mutation. Three patients had been diagnosed with breast cancer, none with previous ovarian cancer. As to the surgery: 3 (42.8%) also underwent bilateral or contralateral risk-reducing mastectomy with reconstruction, and 4 (57.2%) only underwent bilateral salpingo-oophorectomy. All patients are alive and without an active oncologic disease, with mean follow-up of 32 months. Conclusions: In this sample, we did not find any occult tumor in patients submitted to bilateral salpingo-oophorectomy due to BRCA mutation.