Risk-reducing Oophorectomy Research Articles

Uptake of Risk-Reducing Measures, Cascade Testing, and Related Challenges Among Carriers of Breast Cancer-Associated Germline Pathogenic Variants in Mexico.

Genetic cancer risk assessment (GCRA) provides pathogenic variant (PV) carriers with the invaluable opportunity to undertake timely cancer risk-reducing (RR) measures and initiate cascade testing (CT). This study describes the uptake of these strategies and the related barriers among breast cancer-associated germline PV carriers in Mexico. Carriers who were at least 6 months after disclosure of genetic test results at two GCRA referral centers were invited to answer a survey assessing sociodemographic characteristics, awareness of their carrier status and its implications, uptake of RR measures according to international guidelines by PV, CT initiation, and associated challenges. Of the eligible carriers, 246/384 (64%) answered the survey (median age: 44 years). Most were female (88%), married/in domestic partnership (66%), and had personal breast/ovarian cancer history (61%). PVs included BRCA1/2 (75%), CHEK2 (10%), PALB2 (5%), ATM (5%), NF1 (2%), RAD51C (2%), PTEN (1%), and TP53 (1%). Most (87%) participants were aware of their carrier status. When recommended, 37% underwent RR bilateral mastectomy, 48% RR oophorectomy, 70% annual mammogram, and 20% breast magnetic resonance imaging. Challenges hindering the uptake of RR measures included financial limitations (67%), lack of recommendation by their physician (35%), and fear (24%). Nearly all (98%) claimed sharing their results with their relatives. CT was initiated in 63% of families and was associated with carriers being married/in domestic partnership (P = .04) and believing GCRA was useful (P < .001). Despite the resource-constrained setting, relevant rates of RR measures and CT were observed. Targeted interventions to reduce out-of-pocket expenses and improve patient-physician communication and patients' understanding on carrier status are warranted to enhance the overall benefit of GCRA and ultimately improve the provision of patient-centered care to both carriers and their at-risk relatives.

Survival outcomes of BRCA1/BRCA2 mutated breast cancers: Study from a tertiary care cancer centre in India.

e22546 Background: There exists a discrepancy amongst various studies over the years on survival outcomes of BRCA (Breast cancer susceptibility gene) mutated breast cancers. Prevalence of BRCA mutation varies from 10 to 18% among Indian population and there is a paucity of data on the survival outcomes of this population. Methods: This ambispective observational study assessed the survival outcomes of 71 BRCA mutated breast cancer patients, treated with uniform protocol at AIIMS New Delhi between January 2014 to December 2022, using survival analysis and cox regression methods. Results: Amongst the 71 patients, BRCA1 and BRCA2 mutated cases were 52 (73.2%) and 19 (26.8%) respectively. The median age was 39 years (24-63 years) in both the groups. Positive family history for malignancy (BRCA1- 69.2% vs BRCA2- 36.8%) and incidence of Triple negative histology (BRCA1-82.7% VS 36.8%) were more commonly associated with BRCA1 positivity. Eight patients (11.3%) had synchronous cancer, most common being a contralateral breast primary. 4 patients (5.6%) developed metachronous cancer. Eighty percent of patients were premenopausal at presentation. There was no difference in stage at presentation, incidence of synchronous and metachronous cancers across both the groups. Of 71 patients, 18 (25%) and 17 (24%) patients underwent risk reducing mastectomy and risk reducing oophorectomy respectively. Thirty five (49.3%) presented with stage I &amp; II disease, while 28 (34.4%) and 7 (9.9%) presented with stage III and metastatic disease respectively. Forty seven patients (67.1%) received neoadjuvant chemotherapy with pathologic complete response rate of 42.5% which was uniform among both the groups. Over the study period, 10 (14.1%) patients had disease relapse with 7 (70%) being metastatic and 3 patients died of the disease. With a median follow up of 36.9 months, 3-year disease free survival (DFS) was 84.2% (BRCA1: 81.1% vs BRCA2: 93.1%) and overall survival (OS) was 94.7% for both groups. Median DFS and OS were not achieved. BRCA type, receptor status, age and menopausal status were not predictors of survival in our study. Conclusions: In our study population of BRCA1/BRCA2 mutated breast cancer, survival outcomes were comparable to historical cohorts of Indian breast cancer patients. Thus, BRCA mutation positivity doesn’t seem to have any prognostic significance in breast cancer outcome.

Risk-Reducing Salpingectomy And Other Strategies For Prevention Of Ovarian And Tubal Carcinoma

Objective: To provide a review of most current evidence and data for risk-reducing strategies used in prevention of ovarian cancer. Methods of study selection: PubMed was used as a search tool for articles with key words focusing on current strategies on prevention of ovarian cancer such as “risk-reducing salpingectomy, “risk-reducing salpingo-oophorectomy, “salpingectomy with delayed oophorectomy”. General consensus and society guidelines from leading organizations such as Society of Gynecologic Oncology, American Cancer Society, and American College of Obstetricians and Gynecologists were reviewed and summarized in this review article with supporting evidence and research studies on most current riskreduction strategies for prevention of ovarian and tubal carcinoma. Result: There is growing evidence that high-grade serous ovarian carcinoma arises in the fallopian tube in the form of serous tubal intraepithelial carcinoma (STIC). Therefore, opportunistic salpingectomy has been increasingly offered at the time of routine benign gynecologic surgery. Risk-reducing bilateral salpingo-oophorectomy has been shown to reduce risk of ovarian cancer up to 90% and offered to women with high hereditary predisposition for ovarian cancer. Riskreducing salpingectomy with delayed oophorectomy (SDO) has been suggested in younger women to balance the effects of infertility and surgically induced menopause resulting from oophorectomy. Conclusion: Combined oral Contraceptive COCs confer long-term protection against ovarian cancer with reported 20% reduction for every 5 years of use, which have been cited as a confounding factor in most of the published studies. Women who used HRT (estrogen alone or combined estrogen and progesterone) carry 20% higher risk of ovarian cancer compared to never-users. The associated increased risk of cervical and breast cancer with COCs/HTR use, have recently let women prefer the RRSO over COCs for prevention of ovarian cancer. Bilateral risk reducing Salpingo-oophorectomy (RRSO) at the age of 40–45 in BRCA1 and 45–50 in BRCA2 mutation carriers is recommended to be the primary approach for risk reduction of ovarian cancer. There is well-supported evidence of lowering the risk of ovarian cancer in high-risk population by 90%. The American college of obstetrics and gynecology committee opinion, recommended opportunistic salpingectomy for the primary prevention of ovarian cancer in a woman already undergoing pelvic surgery for another indication. Bilateral salpingectomy at the time of cesarean delivery is recommended to replace the tubal ligation as the method of choice for sterilization performed with cesarean delivery. The novel alternative procedure of Risk-reducing Salpingectomy with delayed risk-reducing oophorectomy (RRSO-RRO) have growing attention as a better alternative to improve the menopause-related morbidity and quality of life.

Effect of Inquiry-Based Stress Reduction on Well-being and Views on Risk-Reducing Surgery Among Women With BRCA Variants in Israel

The high risk for breast and ovarian cancers conferred by being a carrier of BRCA1 or BRCA2 germline variant can negatively impact physical and psychological well-being. Novel nonpharmacological interventions on well-being in women with BRCA variants have rarely been reported. To determine the effect of a 12-week inquiry-based stress reduction (IBSR) program on psychological well-being, sleep quality, psychosocial variables, and attitudes toward risk-reducing surgical procedures among women in Israel who carried BRCA variants. This randomized clinical trial had a 12-week intervention period and a 12-week follow-up period. It was conducted between April 1, 2017, and July 31, 2020. Participants were recruited from the Meirav Breast Center at the Sheba Medical Center, Israel, and the intervention was conducted in Tel Aviv, Israel. The cohort included women with BRCA variants. Data were analyzed from August 1 to December 1, 2020. Women were randomly assigned to the 12-week IBSR program or standard care. The IBSR technique is based on the skills of mindfulness, inquiry, and cognitive reframing. The intervention included standardized, weekly group meetings conducted throughout 12 weeks. Standard care included semi-annual breast examinations and breast magnetic resonance imaging (alternating), a gynecological examination, a transvaginal ultrasonographic examination, and CA-125 serum determination. Differences between the groups were tested using mixed-effects models in an intent to treat analysis. The primary outcome was psychological well-being, including 6 parameters: autonomy, personal growth, positive relationships, control of the environment, goals in life, and self-acceptance. Secondary outcomes included sleep quality, attitudes toward risk-reducing surgical procedures, and psychosocial variables. Questionnaires were administered at baseline (T1), at completion of the 12-week intervention (T2), and 12 weeks after completion of the intervention (T3). Overall, 100 women (mean [SD] age, 41.37 [11.06] years) completed the study, with 50 randomized to the intervention group and 50 randomized to the control group. Mean (SD) time from variant discovery was 4.7 (3.3) years. There were no differences between the intervention and control groups in baseline mean (SD) scores of psychological well-being parameters (autonomy: 55.20 [11.12] vs 56.77 [9.90]; environmental control: 56.30 [11.98 vs 58.51 [11.41]; positive relationships: 63.10 [15.91] vs 68.10 [9.86]; goals in life: 60.00 [14.12] vs 64.82 [10.57]; self-acceptance: 55.02 [16.62] vs 60.32 [13.50]) except personal growth (63.70 [14.66] vs 68.85 [8.07]). The IBSR group, compared with the control group, experienced better mean (SD) scores on all psychological well-being parameters at T2 (autonomy: 63.64 [8.35] vs 54.73 [10.41]; environmental control: 63.95 [10.05] vs 57.45 [11.43]; personal growth: 73.00 [8.34] vs 65.76 [10.95]; positive relationships 71.17 [9.99] vs 65.06 [12.58]; goals in life: 67.57 [8.88] vs 61.18 [12.87]; self-acceptance: 66.93 [11.15] vs 58.09 [15.55]) and at T3 (autonomy: 62.68 [9.05] vs 56.12 [10.64]; environmental control: 64.55 [10.28] vs 59.35 [12.98]; personal growth: 72.00 [8.06] vs 67.15 [11.82]; positive relationships: 71.24 [9.78] vs 66.92 [12.37]; goals in life: 68.33 [8.54] vs 62.92 [13.24]; self-acceptance: 66.84 [11.35] vs 58.97 [17.03]). Individuals in the IBSR group also experienced statistically significant improvements in sleep quality (mean [SD]: T1, 7.35 [3.97]; T3, 4.63 [3.21], P < .001), whereas the control group experienced no statistically significant difference. Women in the intervention group had a more favorable consideration of risk-reducing oophorectomy, from 7 women (14%) who refused to consider oophorectomy at T1 to 1 woman (2%) who refused to consider it at T3 (P = .04), and similar change in consideration of mastectomy: from 23 women (46%) who refused to consider mastectomy at T1 to 13 women (29%) who refused to consider it at T3 (P < .001). This randomized clinical trial found that IBSR improved psychological well-being and led to a more favorable view on risk-reducing surgical procedures for at least 6 months among women in Israel who carried BRCA variants. These results suggest that IBSR may be implemented as a self-practice tool to enhance the well-being of individuals who carry BRCA variants and support them in their decision-making processes. ClinicalTrials.gov Identifier: NCT03162276.

The evolving role of the Women's Health Specialist in cancer prevention and survivorship.

This review provides a framework for primary care physicians, internists, family doctors, NP's, PA's, and oncologists caring for women-henceforth referred to as Women's Health Specialists-to identify and screen patients who may be at high risk for inherited cancer syndromes; an intervention referred to as previvorship care. For women who undergo risk-reducing oophorectomy, survivorship care is critical to optimizing quality of life thereafter. In this paper, we review management of the unique survivorship needs and management options for women at risk for or with a cancer diagnosis, highlighting the importance of interdisciplinary care. To review the available previvorship and survivorship management strategies, a Pub Med search was performed using keywords "survivorship," "genetics," "cancer," "menopause," "hormone therapy," "screening" in addition to review of guidelines, position statements and expert, and committee opinions from the American College of OBGYN, the American Society of Clinical Oncology, The North American Menopause Society, the National Comprehensive Cancer Network , and the American Society for Reproductive Medicine. Women's Health Specialists are in a unique position to identify and screen women who may be at risk for inherited cancer syndromes as well as provide necessary survivorship management following transition from their oncologists' care.

Selected Articles from This Issue

A prior cancer diagnosis is common among solid organ transplant candidates, and immunosuppressive medications administered to transplant recipients may increase recurrence risk. Engels and colleagues used data from the United States transplant registry and 13 cancer registries to assess cancer-specific survival among 10,524,326 cancer patients, 5425 of whom (0.05%) subsequently underwent transplantation. Transplantation was not associated with decreased cancer-specific survival for any cancer site. Protective associations were observed for patients with breast cancer, non-Hodgkin lymphoma, and myeloma. These results partly reflect careful transplant candidate selection and do not demonstrate a detrimental effect of immunosuppression on cancer-specific survival, supporting current management strategies.Chang and colleagues analyzed BOp. data across 3,460 adults in Wave 1 of the PATH Study, including current exclusive smokeless tobacco (ST) use among never smokers (primary ST users) and former smokers (secondary ST users), exclusive cigarette smokers, dual users of ST and cigarettes, former smokers, and never tobacco users. BOPH concentrations among primary ST users were similar to never tobacco users and former smokers. Dual users had significantly higher sICAM-1, IL-6, and F2-isoprostane compared to never tobacco users, but looked similar to exclusive smokers. ST use alone and in combination with smoking may affect levels of inflammatory and oxidative stress levels.Recruitment of stromal cells into the tumor microenvironment may influence disease progression and prognosis in breast cancer. By applying machine learning algorithms to digitized H&amp;E-stained sections for 2,084 breast cancer patients from China, Poland, and the United States, Abubakar and colleagues characterized tumor-associated stromal cellular density (SCD) as the percentage of tumor-stroma that is occupied by nucleated cells. The authors found increasing SCD to be independently predictive of poor clinical outcomes among patients with hormone receptor-positive breast cancer from all three study populations. The findings suggest that SCD assessment on H&amp;E-stained sections, which are routinely performed and widely available, could help refine prognostic assessment and treatment decision-making for patients with hormone receptor-positive breast cancer.Many women undergo risk-reducing oophorectomy (RRO) for ovarian cancer prevention at the time of hysterectomy. The abrupt decline in circulating hormones after RRO may impact body composition, particularly in premenopausal women. In this diverse national sample of women, Karia and colleagues observed higher total and regional (trunk, arms, legs) fat mass and lower lean mass among women with hysterectomy and RRO than those with hysterectomy alone or no surgery. Point estimates were stronger among women &lt;45 years at surgery and those with a normal BMI. Longitudinal studies are needed to assess changes in body composition after RRO and to test interventions to mitigate these effects.

Cancer risk management and family communication of genetic test results among women with inherited breast cancer genes.

1532 Background: Identification of inherited breast cancer may guide care, with benefits amplified through family testing. Methods: Females with a pathogenic/likely pathogenic (P/LP) variant in BRCA1/2, PALB2, CHEK2, and/or ATM were surveyed about cancer risk management, family communication of genetic test results, and family testing. Comparisons were made across genes. Results: The 235 participants with P/LP variants (186 BRCA1/2, 28 PALB2, 15 CHEK2, and 6 ATM) had a median age of 54 and 61% had a prior breast cancer diagnosis. For women with P/LP variants in BRCA1/2, PALB2, and ATM/CHEK2, bilateral mastectomy rates were 79%, 61%, and 52%, respectively; and risk-reducing oophorectomy rates were 89%, 30%, and 37%, respectively. All women with PALB2 and ATM/CHEK2 P/LP variants with a bilateral mastectomy had a personal or family history of breast cancer; however, only 27% of those with a risk-reducing oophorectomy had a family history of ovarian cancer. Family communication of genetic test results and family testing rates were higher for those with P/LP variants in BRCA1/2 compared to others. Conclusions: Bilateral mastectomy and risk-reducing oophorectomy were relatively common among women with PALB2 and ATM/CHEK2 P/LP variants in our study, suggesting overtreatment through risk-reducing surgery. Furthermore, strategies to improve family communication of genetic test results and family testing are needed to amplify testing benefits.

Risk-Reducing Oophorectomy and Breast Cancer Risk Across the Spectrum of Familial Risk.

There remains debate about whether risk-reducing salpingo-oophorectomy (RRSO), which reduces ovarian cancer risk, also reduces breast cancer risk. We examined the association between RRSO and breast cancer risk using a prospective cohort of 17 917 women unaffected with breast cancer at baseline (7.2% known carriers of BRCA1 or BRCA2 mutations). During a median follow-up of 10.7 years, 1046 women were diagnosed with incident breast cancer. Modeling RRSO as a time-varying exposure, there was no association with breast cancer risk overall (hazard ratio [HR] = 1.04, 95% confidence interval [CI] = 0.87 to 1.24) or by tertiles of predicted absolute risk based on family history (HR = 0.68, 95% CI = 0.32 to 1.47, HR = 0.94, 95% CI = 0.70 to 1.26, and HR = 1.10, 95% CI = 0.88 to 1.39, for lowest, middle, and highest tertile of risk, respectively) or for BRCA1 and BRCA2 mutation carriers when examined separately. There was also no association after accounting for hormone therapy use after RRSO. These findings suggest that RRSO should not be considered efficacious for reducing breast cancer risk.

Background parenchymal enhancement and fibroglandular tissue on breast MRI in women with high genetic risk: Are changes before and after risk-reducing salpingo-oophorectomy associated with breast cancer risk?

BackgroundParenchymal enhancement and fibroglandular tissue on breast MRI in women with high genetic risk: are changes before and after risk-reducing salpingo-oophorectomy associated with breast cancer risk? ObjectiveTo evaluate changes in the level of background parenchymal enhancement (BPE) and amount of fibroglandular tissue (FGT) on breast MRI before and after risk-reducing oophorectomy (RRSO), and to determine whether these changes correlate with ultimate breast cancer risk. Materials and methodsThe cohort included 146 women with high genetic risk who had undergone pre- and post-RRSO breast MRI. BPE level and FGT amount were retrospectively graded according to BI-RADS classification. Initial values and changes were compared in women with or without later breast cancer after RRSO. Hazard ratios (HR) were estimated using Cox univariate models. ResultsPatients with initial moderate (BI-RADS C category) BPE had a higher risk of subsequent breast cancer of HR = 3.9 (95% CI [1.1–14.3]; p = 0.04) compared to patients with initial minimal (BI-RADS A) BPE. A categorical BPE decrease after RRSO, versus no change, was associated with a higher cancer risk (HR 2.2, 95% CI [1.04–4.8]; p = 0.04). Initially dense (BI-RADS 3 category) FGT correlated with an increased cancer risk compared to fatty (BI-RADS 1 category) parenchyma (HR 8.3, 95% CI [1.1–64]; p = 0.04). After RRSO, there was a trend for higher cancer risk related to a categorical FGT decrease (HR 2.3, 95% CI [0.9–35.4]; p = 0.06). ConclusionPatients in whom BPE decreases after RRSO might be at higher risk of subsequent breast cancer compared to patients with stable BPE. This finding is consistent with the concept of increased risk associated with high initial BPE, which could be of higher clinical relevance than post-RRSO BPE reduction. A similar trend was observed with high initial FGT.

Challenging perspectives: Prescribing hormone replacement in premature ovarian insufficiency

The incidence of premature ovarian insufficiency (POI) is increasing in the general population with, among other reasons, more women surviving cancer treatments or having risk-reducing prophylactic oophorectomy due to BRCA status. The ovary is a vital endocrine gland and lost hormones need replacing to maintain system-wide health until the average age of the menopause (51 years). The combined oral contraceptive or hormone replacement therapy are recognised treatment choices for POI, but choosing the individual prescription may seen daunting. Through simple risk–benefit assessment and understanding modes of action, the nurse prescriber can guide effective decision-making and support long-term compliance.

Abstract P6-09-01: Risk-reducing oophorectomy and breast cancer risk across the spectrum of familial risk using a prospective family study cohort (ProF-SC)

Abstract Background: Whether risk-reducing salpingo oophorectomy (RRSO) reduces breast cancer risk in addition to reducing ovarian cancer risk is controversial with some arguing that the previous evidence of a reduction in breast cancer risk from RRSO was due to bias. Evidence from independent prospective cohorts of high-risk women is needed to resolve this controversy. Methods: Using a prospective family study cohort of 17,810 women unaffected with breast cancer at baseline, we examined the association between RRSO and breast cancer risk using Cox Proportional Hazards models. We compared results estimating RRSO as a non-time-dependent variable to results treating RRSO as a time-dependent variable, because failing to account for the time-varying nature of a covariate person- time prior to RRSO, should it exist, will incorrectly attribute the cancer-free person-time to RRSO. We separately examined the association with RRSO in BRCA1 and BRCA2 mutation carriers and non-carriers, and further performed gene-stratified analyses in women with BRCA1 and BRCA2 only. We also assessed multiplicative interactions with underlying familial risk profile (FRP), defined as total lifetime risk estimated from the Breast Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm (BOADICEA) model. Results: During a median 10.7 years of follow-up (maximum 23.7 years), we observed 1,040 incident cases of breast cancer with an average age at diagnosis of 55.8 years and average age at enrollment into the cohort of 46.8 years. A total of 2434 (14%) women reported at baseline having a RRSO. We observed decreased risk of breast cancer associated with RRSO for both BRCA1(N= 650) and BRCA2(N=557) mutation carriers when RRSO was treated as a fixed covariate (HR= 0.60, 95% CI=0.40-0.92 and HR= 0.40, 95%CI = 0.23-0.69, respectively). In contrast, when we treated RRSO as a time-varying covariate, for both BRCA1 and BRCA2 carriers, we no longer observed a decreased risk for BRCA1 and BRCA2 carriers (HR= 1.67, 95% CI=1.05-2.67 and HR= 0.97, 95%CI = 0.53-1.80, respectively). There was no association between RRSO and breast cancer risk for non-carriers (N=16,603), whether we treated RRSO as a fixed or time varying covariate (HR= 0.88, 95% CI=0.72-1.08 and HR= 1.06, 95%CI = 0.85-1.30, respectively). Conclusions: Our findings provide an independent replication that the reduced risk of breast cancer previously observed in BRCA1 and BRCA2 mutation carrier women may be from bias in counting person-time. Clinical management of high-risk women should counsel based on the reduced risk of ovarian cancer from RRSO, but not breast cancer. Citation Format: Terry MB, Phillips KA, Daly MB, Andrulis IL, Liao Y, Ma X, Zeinomar N, MacInnis RJ, Dite GS, John EM, Buys SS, Hopper JL. Risk-reducing oophorectomy and breast cancer risk across the spectrum of familial risk using a prospective family study cohort (ProF-SC) [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P6-09-01.

Abstract P4-06-14: Voice of cancer patients: Association of family history with genetic mutations in breast and ovarian cancer

Abstract There are specific guidelines for testing germline mutations in patients with breast cancer. Besides BRCA 1 and 2, germline mutations of multiple other genes are being recognized as risk factors for breast and ovarian cancers and hence more patients are being tested using multigene panels. Many patients share their experiences as freely shared messages in online forums. In this study, we use our automated system (VoCP) to analyze these messages to understand awareness of genetic testing in breast cancer patients and some factors that lead to their genetic testing. Method: We collected 15.13 million unique messages (by 987,189 users) from 37 unrestricted cancer forums that provide clinically relevant information. We built custom ontologies for genetic tests; breast, ovarian and other cancers; risk reducing mastectomy and oophorectomy; and screening. We then used VoCP that uses techniques from Big Data Science and Artificial Intelligence (e.g., deep learning, topic modeling, information retrieval, and natural language processing) to extract relevant information from these messages. Results: Out of 15.13 million, 30,074 messages from 7,838 distinct users were discussing genetic testing. Mutations that were discussed most include: · BRCA1/BRCA2 (28,130 messages); 954 patients were positive · PALB2 (218 messages); 114 were positive · CHEK2 (315 messages); 149 were positive · TP53 (180 messages); 55 were positive · BRIP1 (76 messages); 36 were positive · CDH1 (128 messages); 12 were positive · NBN (80 messages); 28 were positive · STK11 (48 messages); 2 were positive · RAD50/ RAD51C (39 messages/48 messages) Association with family history of cancer: 3,083 messages mentioned positive family history and some mentioned several cancers in their family; these messages discussed the following cancers: · Breast cancer: 2,243 massages · Ovarian cancer: 830 massages · Colon cancer: 247 messages · Pancreatic cancer: 121 massages · Prostate cancer: 206 massages · Lung cancer: 138 messages Out of 954 BRCA 1 and 2 positive patients, · 279 messages indicated their family members were tested for BRCA 1 and 2 · 156 messages indicated positive mutations were found in family members · 23 messages indicated that male members of family were also being tested Also, out of 954 BRCA 1 and 2 positive patients, · 333 mentioned opting for bilateral mastectomy and 117 talked about getting Prophylactic Bilateral Salpingo Oophorectomy · 309 messages talked about ovarian cancer once they found out that they have BRCA mutation Discussion:There is increasing awareness of genetic testing and germline mutations in addition to BRCA 1 and 2 in breast cancer. Positive family history of cancer is mentioned in 10% of patients seeking genetic testing. VoCP reliably provides meaningful insights from patients' point of view to their treatment and their concerns; it also gives insight into unmet needs where more resources and research should be focused. We plan to use VoCP for further segmenting these 30,074 messages to understand other attributes and awareness among such patients. Citation Format: Aggarwal S, Sharma R, Sharma R, Aggarwal A. Voice of cancer patients: Association of family history with genetic mutations in breast and ovarian cancer [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P4-06-14.

Abstract P6-12-08: Fertility interest, management and outcomes in young BRCA+ breast cancer survivors

Abstract Background: Young women with BRCA mutations may face fertility issues given the standard recommendation for risk-reducing oophorectomy after childbearing has been completed or before age 40. Potential transmission of the affected gene to future progeny may also be a concern. Little is known regarding the perspectives, management, and outcomes of young breast cancer survivors with BRCA mutations, who also face risks of recurrent disease and treatment effects on fertility. Methods: As part of a multi-center, prospective cohort study of newly diagnosed breast cancer (BC) at age ≤40 years enrolling between 2006-2016, we identified women with stage I-III BC who had self-reported results of genetic testing. Participants are surveyed at baseline then annually regarding their breast cancer treatment, genetic testing, fertility interest, pregnancy attempts, and pregnancies. Chi-square tests were used to compare proportions of carriers vs non-carriers who were interested in future biologic children, took steps to preserve fertility, underwent bilateral oophorectomy, attempted pregnancy, and became pregnant in the 5 years following diagnosis. Results: Carriers (n=104) and non-carriers (n=662) were similar in age and stage, but greater proportions of carriers had ER negative disease and received chemotherapy (Table 1). The proportion of carriers and non-carriers interested in future biologic children was similar prior to diagnosis (51% vs 38%; p=0.18), 1 year following diagnosis (30% vs 27%; p=0.44), and 5 years following diagnosis (14% vs 15%; p=0.26). Similar proportions of carriers (12%) and non-carriers (14%) took steps to prevent infertility prior to treatment. Greater proportions of carriers indicated that concern about having a child at higher risk of breast cancer affected their interest in future biologic children (15% vs 4%, p=0.02) and underwent bilateral oophorectomy (61% vs 9%, p&amp;lt;0.0001), but there was no difference in rates of pregnancy attempts (15% vs 11%, p=0.62), or pregnancies (12% vs 8%, p=0.36) in the five years following diagnosis. Conclusion: Young breast cancer survivors with known BRCA mutations have similar interest in future fertility and both attempt and become pregnant at similar rates to non-carriers in the five years following diagnosis. Impact of specific BRCA mutation (1 or 2), ER status of tumor, and timing of pregnancy attempts will be explored in future analyses. Table 1: BRCA mutation carriers, n (%)Non-carriers, n (%)X2 p-valueAge 0.47&amp;lt;3018 (17)86 (13) 31-3529 (28)201 (30) 36-4057 (55)375 (57) Stage 0.73I40 (39)260 (39) II46 (44)307 (46) III18 (17)95 (14) Partnered 0.44Yes77 (74)509 (77) No27 (26)148 (22) Missing0 (0)5 (1) Children pre-diagnosis 0.33Yes62 (60)427 (64) No42 (40)235 (36) Phenotype &amp;lt;0.0001ER and/or PR+48 (46)490 (74) ER and PR-56 (54)171 (26) Missing0 (0)1 (0) Adjuvant hormones &amp;lt;0.0001Yes44 (42)488 (74) No60 (58)174 (26) Chemotherapy 0.003Yes96 (92)529 (80) No8 (8)132 (2) Missing0 (0)1 (0) Citation Format: Poorvu PD, Gelber SI, Ruddy KJ, Seiger K, Tamimi RM, Peppercorn J, Schapira L, Borges VF, Come SE, Partridge AH, Rosenberg SM. Fertility interest, management and outcomes in young BRCA+ breast cancer survivors [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P6-12-08.

Adaptation of couples living with a high risk of breast/ovarian cancer and the association with risk-reducing surgery.

Women who carry BRCA1/2 mutations have a significantly elevated risk for breast and ovarian cancer. The positive test result and subsequent decisions about risk reducing behaviors can evoke distress, anxiety and worry. Psychological adaptation, or the process of coming to terms with the implications of a health threat, is an understudied construct in BRCA1/2 carriers. Little is known about adaptation and how it relates to other aspects of living at high risk for cancer. Even less is understood about adaptation among partners of BRCA1/2 carriers, and its relationship to adaptation in high risk individuals. Women at increased risk of breast/ovarian cancer (N = 103) and a subset of partners (N = 39) completed questionnaires that assessed risk management decisions (e.g. screening, risk-reducing surgery), dyadic coping, and the outcome of psychological adaptation. Women who had undergone risk-reducing mastectomy (RRM) had significantly higher levels of adaptation than those who had not (t = 5.5, p < 0.001, d = 1.10). Partners of women who had undergone RRM also had higher levels of adaptation than partners of women who had not undergone RRM (t = 3.7, p = 0.01, d = 0.96), though this association was not statistically significant when controlling for carriers' adaptation. Undergoing risk-reducing oophorectomy was not associated with adaptation for BRCA1/2 carriers or their partners. Risk-reducing mastectomy is a significant event in the process of adapting to life at risk for hereditary cancer. Further, adaptation among partners is highly related to adaptation in carriers. These results aid in the understanding of the experience of couples living with cancer risk and the medical decisions related to adaptation.

Lessons of Risk-Reducing Oophorectomy

Lessons of Risk-Reducing Oophorectomy

Disparities in cancer risk management among BRCA carriers across a diverse sample of young black, Hispanic, and non-Hispanic white breast cancer survivors.

LBA1504 Background: Rates of risk-reducing bilateral mastectomy (RRM) or risk-reducing prophylactic oophorectomy (RRSO) among BRCA carriers are based on studies of non-Hispanic whites (NHW), with little known among blacks or Hispanics. Methods: A population-based sample of NHW, black, and Hispanic women diagnosed with invasive BC &lt; age 50 in 2009-12 were recruited through the Florida State Cancer Registry and completed a baseline survey. Among the subset of BRCA carriers, we compared risk management for: 1) ovarian cancer (OC) through RRSO; and 2) BC through RRM or MRI screening, by calculating percentages and conducting logistic regression to control for other variables. Results: Of 1570 participants, 884 reported BRCA testing. Of the 91 BRCA carriers, 1) RRSO was 71% (36/51) among NHW, 32% (9/28) among blacks, and 83% (10/12) among Hispanics; 2) either breast MRI or RRM was 98% (50/51) among NHW, 85.7% (24/28) among blacks, and 100% (12/12) among Hispanics. BC risk management modality differed across groups, with lower rates of RRM among blacks (67%) compared to Hispanics (83%) and NHW (94%). After controlling for age at enrollment, time since diagnosis, income, family history of BC, family history of OC and private insurance at diagnosis: 1) Hispanics and NHW were significantly more likely than blacks to have RRSO (p = 0.01 and 0.02 respectively); and 2) NHW were also significantly more likely than blacks to have RRM (p = 0.03), although Hispanic race approached statistical significance (p = 0.10). Conclusions: The racial disparities in uptake of RRSO observed among blacks is particularly concerning given that RRSO is strongly recommended as the main OC prevention option due to the absence of effective OC early detection methods. The benefit from genetic testing comes from uptake of cancer risk management options, rather from testing itself. Future studies are needed to better understand and develop methods to improve cancer risk management practices across all populations.

Risk of contralateral breast cancer in BRCA1 and BRCA2 mutation carriers: a 30-year semi-prospective analysis.

BRCA1 and BRCA2 mutation carriers have an increased risk of contralateral breast cancer after primary breast cancer. Risk reduction strategies are discussed after assessment of risk factors for developing contralateral breast cancer. We assessed potential risk factors that could be of use in clinical practice, including the novel use of single nucleotide polymorphisms (SNP) testing. 506 BRCA1 and 505 BRCA2 mutation carriers with a diagnosis of breast cancer were observed for up to 30 years. The risk of a contralateral breast cancer is approximately 2-3% per year, remaining constant for at least 20 years. This was similar in both BRCA1 and BRCA2 carriers. Initial breast cancer before age 40-years was a significant risk factor, which was more pronounced in BRCA1 patients. The effect of risk-reducing oophorectomy on contralateral breast cancer risk may be overestimated because of bias. No significant association was found between overall breast cancer risk SNP score and contralateral breast cancer development. Young mutation carriers, particularly those with BRCA1 mutations, who develop breast cancer have a significantly higher risk of developing contralateral breast cancer, remaining constant for over 20 years. Contralateral risk-reducing mastectomy should be considered in this group, in particular as there is a survival benefit. Caution is advised when counselling women considering risk-reducing oophorectomy as, after accounting for statistical bias, the associated risk reduction was found to be non-significant, and potentially smaller than has been previously reported. SNP testing did not add any further discriminatory information when assessing contralateral breast cancer risk.

Intentions for risk-reducing surgery among high-risk women referred for BRCA1/BRCA2 genetic counseling.

Genetic testing for breast and ovarian cancer susceptibility is now part of routine clinical practice. Although rates of risk-reducing surgery following genetic testing have been increasing, little is known about attitudes toward risk-reducing surgery in women prior to genetic counseling and testing. This study examines correlates of patient intentions to undergo risk-reducing mastectomy (RRM) and risk-reducing oophorectomy (RRO). Participants were 696 women, ages 21-85, who sought breast cancer gene 1 and 2 (BRCA1/2) genetic counseling and had at least a 10% risk of carrying a mutation. The sample included women who were affected with breast or ovarian cancer and unaffected women with a known familial BRCA1/2 mutation. Participants completed a precounseling telephone questionnaire. Prior to receiving genetic counseling, 23.3% of participants were considering RRM and 42.5% were considering RRO. Variables that were independently associated with RRM intentions were cancer-specific distress (OR = 1.14, 95% CI = 1.03-1.26), perceived risk of breast cancer (OR = 1.16, 95% CI = 1.05-1.28), education (OR = 1.76, 95% CI = 1.03-2.99), and age (OR = 0.96, 95% CI = 0.95-0.98). Predictors of RRO intentions were perceived risk for ovarian cancer (OR = 1.25, 95% CI = 1.14-1.37), perceived risk of carrying a BRCA1/2 mutation (OR = 1.74, 95% CI = 1.15-2.62), marital status (OR = 1.92, 95% CI = 1.34-2.76), and age (OR = 1.02, 95% CI = 1.00-1.03). Because precounseling intentions predict subsequent risk-reducing surgery decisions, this study identified patient factors associated with surgical intentions. These factors reinforce the critical role for pretest genetic counseling in communicating accurate risk estimates and management options, and addressing psychosocial concerns, to facilitate informed decision making regarding RRM and RRO.

A Major Step Forward for BRCA1/2-Related Cancer Risk Management

A Major Step Forward for <i>BRCA1/2</i>-Related Cancer Risk Management

A pilot intervention addressing sexual dysfunction after risk-reducing oophorectomy.

9644 Background: Women at high risk for ovarian cancer due to BRCA1 or BRCA2 mutation or family history are recommended to undergo prophylactic bilateral salpingo-oophorectomy (PBSO) after age 35 or completion of childbearing. This potentially life-saving surgery leads to premature menopause, frequently resulting in profound sexual dysfunction. We developed and piloted the first psychoeducational intervention for managing sexual dysfunction in young women after PBSO. Methods: This single-arm multi-modal pilot intervention study included a single half day session with educational modules about sexual health education, relaxation training, and cognitive behavioral therapy (CBT) skills to manage symptoms, followed by tailored telephone counseling. Self-report assessments, including the 19-item Female Sexual Function Index (FSFI) and a 10-item measure of sexual knowledge after PBSO were completed at baseline and two months post-intervention. Eligible women had PBSO for risk-reduction, current age ≤ 49, and endorsed at least one symptom of sexual dysfunction. Study endpoints include feasibility and effectiveness. Results: 36 women enrolled and completed pre- and post- assessments. Median age was 44 years (range 36-49) and median time since PBSO was 3.2 years (range 0.75-12.3). FSFI scores improved significantly from baseline to post-intervention for the desire (p = 0.003), arousal (p = 0.001), and satisfaction (p = 0.031) domains, as well as on the full scale score (p = 0.005). In addition, 60% of participants demonstrated improved knowledge scores about managing sexual dysfunction after PBSO following the intervention. Conclusions: The current intervention builds upon recent advances in CBT and sexual health education to address this much-neglected problem after PBSO. Results from this promising pilot intervention provide compelling preliminary data to move toward conducting a randomized clinical trial. Reducing post-PBSO distress, a valuable goal in its own right, may ultimately improve uptake of this potentially life-saving procedure in a high-risk population, as loss of sexual functioning is one of the reasons mutation carriers give for rejecting surgical risk-reduction.