Development of an Electronic Decision Aid Tool to Facilitate Mainstream Genetic Testing in Ovarian Cancer Patients.

BACKGROUND: Multigene panel testing is an important component of cancer treatment plans and risk assessment, but there are many different panel options and choosing the most appropriate panel can be challenging for health care providers and patients. Electronic tools have been proposed to help patients make informed decisions about which gene panel to choose by considering their preferences and priorities. MATERIALS AND METHODS: An electronic decision aid (DA) tool was developed in line with the International Patient Decision Aids Standards collaboration. The multidisciplinary project team collaborated with an external health care communications agency and the MGH Cancer Center Patient and Family Advisory Council (PFAC) to develop the DA. Surveys of genetic counselors and patients were used to scope the content, and alpha testing was used to refine the design and content. RESULTS: Surveys of genetic counselors (n = 12) and patients (n = 228) identified common themes in discussing panel size and strategies for helping patients decide between panels and in identifying confusing terms for patients and distribution of patients' choices. The DA, organized into 2 major sections, provides educational text, graphics, and videos to guide patients through the decision-making process. Alpha testing feedback from the PFAC (n = 4), genetic counselors (n = 3) and a group of lay people (n = 8) identified areas to improve navigation, simplify wording, and improve layout. CONCLUSION: The DA developed in this study has the potential to facilitate informed decision-making by patients regarding cancer genetic testing. The distinctive feature of this DA is that it addresses the specific question of which multigene panel may be most suitable for the patient. Its acceptability and effectiveness will be evaluated in future studies.

Patient decisions regarding cancer gene panel testing: An exploratory study.

This study examined factors associated with the selection of a specific multi-gene panel test by patients in a cancer genetic counseling clinic. We surveyed patients who received pre-test genetic counseling at the Massachusetts General Hospital Center for Cancer Risk Assessment (CCRA) in 2019 and their genetic counselors to assess demographic and clinical characteristics, patient concerns, and session outcome. Ultimately, 228 eligible participants completed the survey, of whom 85.1% consented to genetic testing. Of those who chose testing, 56.2% selected the largest panel type available, a pan-cancer panel that included both actionable and inactionable genes. White patients were more likely than non-white patients to pursue testing. Among testers, number of testing options offered, participant educational attainment, age, and NCCN Guidelines status were associated with patient choice between four panel options. Some patient concerns, including impact of results on future cancer screening and family dynamics, were also linked to test choice. Several other participant characteristics including income, cancer diagnosis, and family structure did not appear to be predictive of testing choice. Our results confirmed the patient preference for large gene panels and identified a limited number of associations between patient characteristics and concerns and testing choice. We noted however that a significant number of participants did not choose the most commonly selected test, and that test choice is difficult to predict based on clinical and demographic factors. Our results also provide further evidence of well-documented disparities in cancer genetic testing. Study limitations do not allow our findings to be generalized to all cancer genetic counseling patients. Further research is needed to examine how and why patients choose between multiple genetic test options in the cancer setting. This study was one of the first to examine patient choice between a full spectrum of multi-gene panel options.

Mainstreamed genetic testing of breast cancer patients: experience from a single surgeon's practice in a large US Academic Center.

This study evaluated the impact of mainstreamed genetic testing (MGT) on the timing and uptake of testing in an academic breast surgeon's practice. Before September 2019 (pre-MGT phase), a breast surgery practice at Massachusetts General Hospital followed a traditional model of a pre-test consultation with a genetic counselor (GC) following a referral. After September 2019 (post-MGT phase), the same practice offered patients genetic testing in a single clinical encounter with a breast surgeon. We evaluated the waiting time between referral and GC visit in the pre-MGT phase and compared the uptake and positivity rates between both phases. In the pre-MGT phase (204 patients), the median waiting time for GC visit was seven days for patients with a newly diagnosed cancer, 211 days for patients with a personal history of cancer, and 224 days for non-cancer patients who had a family history. A total of 105 (51.5%) patients completed a GC appointment. In the post-MGT phase (202 patients), a significantly higher proportion of patients (88.1%, p < 0.001) consented to genetic testing, while the proportion of patients who tested positive was lower (pathogenic variant: 11.9% vs. 20.0%; variant of uncertain significance: 19.9% vs. 28.0%; p = 0.047). Implementing MGT can reduce the number of clinical visits, significantly shorten patients' wait time to test initiation, and increase the completion of genetic testing. Successful integration of this model relied on the genetic expertise of the breast surgeon involved and the support of the GC team.

Performance of the shared decision-making process scale for use in evaluation of hereditary cancer genetic testing decisions.

This study aimed to evaluate feasibility, acceptability, reliability, and validity of the existing four-item Shared Decision Making (SDM) Process Scale for use in evaluating genetic testing decisions. Patients from a large hereditary cancer genetics practice were invited to participate in a two-part survey after completing pre-test genetic counseling. The online survey included the SDM Process Scale and the SURE scale, a measure of decisional conflict. SDM Process scores were compared to SURE scores to test convergent validity, and respondents were sent a second survey 1 week later to assess retest reliability. The response rate was 65% (n = 259/398) and missing data was low (<1%). SDM scores ranged from zero to four with a mean of 2.3 (SD = 1.1). Retest reliability was good, with intraclass correlation of 0.84, 95% confidence interval (0.79, 0.88). No relationship was found between SDM Process scores and decisional conflict (p = 0.46), likely because 85% of participants reported no decisional conflict. The four-item SDM Process Scale demonstrated feasibility, acceptability, and retest reliability, but not convergent validity with decisional conflict. These findings provide initial evidence for use of this scale to measure patient perceptions of SDM in pre-test counseling for hereditary cancer genetic testing.

A Pooled Electronic Consultation Program to Improve Access to Genetics Specialists.

Innovative service delivery models are needed to increase access to genetics specialists. Electronic consultation (e-Consult) programs can connect clinicians with specialists. At Massachusetts General Hospital, an e-Consult service was created to address genomics-related questions. In its first year, the e-Consult service triaged 153 requests and completed 122 in an average of 3.2 days. Of the 95 e-Consults with actionable recommendations, there was documentation that most ordering clinicians followed through (82%). A variety of providers used the service, although the majority (77%) were generalists. E-Consult models should be considered as one way to increase access to genetics care.

ATM Variants in Breast Cancer: Implications for Breast Radiation Therapy Treatment Recommendations.

PURPOSE: Advances in germline genetic testing have led to a surge in identification of ataxia-telangiectasia mutated (ATM) variant carriers among breast cancer patients, raising numerous questions regarding use of breast radiation therapy (RT) in this population. METHODS: A literature search using PubMed identified articles assessing association(s) between the germline ATM variant status and the risk of toxicity after breast RT. An expert panel of breast radiation oncologists, genetic counselors, and basic scientists convened to review the association between ATM variants and radiation-induced toxicity or secondary malignancy risk and to determine any impact on breast RT recommendations. RESULTS: Carriers of pathogenic variants in ATM have a 2- to 4-fold increased risk for developing breast cancer. ATM variants do not consistently increase risks of toxicities after RT, except possibly among patients with the single nucleotide variant c5557G>A (rs1801516), in whom a small increased risk for the development of both acute and late radiation effects has been identified. In most breast cancer patients with ATM variants, the excess 5-year absolute risk of developing a secondary contralateral breast cancer (CBC) after radiation is extremely low. The exception is in women younger than 45 years old with deleterious rare ATM missense variants, who may be at higher risk for developing a radiation-induced CBC over time. CONCLUSIONS: Adjuvant radiation is safe for most breast cancer patients who harbor ATM variants. The possible exceptions are patients with the variant c5557G>A (rs1801516) and patients younger than 45 years old with certain rare deleterious ATM variants, who may be at higher risk for developing CBC. These latter patients should be counseled regarding this potential risk, and every effort should be made to minimize the contralateral breast dose. However, the inconsistency of published data limits precise recommendations, magnifying the need for further prospective studies and the development of a centralized database cataloging RT outcomes and genetic status.

Transition to telephone genetic counseling services during the COVID-19 pandemic.

The COVID-19 pandemic has significantly disrupted the delivery of healthcare services, including oncology. To ensure continuity of cancer genetic counseling at a large academic medical center while also promoting the safety of patients and staff, our team transitioned to fully remote telephone genetic counseling and testing services within 48 hr. We compare differences in the six weeks following the shift to telephone genetic counseling (post-COVID) to the six weeks preceding the pandemic (pre-COVID). We maintained 99% of our total visit capacity and saw a decrease in patient no-show rate from 9.5% to 7.3%. Of all patients who received telephone genetic counseling, fewer consented to genetic testing as compared to patients seen in-person prior to the pandemic (79% pre-COVID v. 72% post-COVID; p = .012). Four weeks after this cohort was closed for analysis, 96 out of 303 samples (32%) had not been received by the genetic testing laboratory, despite at least one reminder phone call to the patient. In 13 reported instances, a second sample was required (quality not sufficient, lost or mislabeled sample), thus delaying test results. We conclude that a rapid transition to remote genetic counseling and testing allowed uninterrupted access to cancer genetics services during to the COVID-19 pandemic. Patient compliance with sample return and higher rates of sample failure emerge as potential barriers to timely genetic testing under this service delivery model.

ATRAID regulates the action of nitrogen-containing bisphosphonates on bone.

Nitrogen-containing bisphosphonates (N-BPs), such as alendronate, are the most widely prescribed medications for diseases involving bone, with nearly 200 million prescriptions written annually. Recently, widespread use of N-BPs has been challenged due to the risk of rare but traumatic side effects such as atypical femoral fracture (AFF) and osteonecrosis of the jaw (ONJ). N-BPs bind to and inhibit farnesyl diphosphate synthase, resulting in defects in protein prenylation. Yet, it remains poorly understood what other cellular factors might allow N-BPs to exert their pharmacological effects. Here, we performed genome-wide studies in cells and patients to identify the poorly characterized gene, ATRAID Loss of ATRAID function results in selective resistance to N-BP-mediated loss of cell viability and the prevention of alendronate-mediated inhibition of prenylation. ATRAID is required for alendronate inhibition of osteoclast function, and ATRAID-deficient mice have impaired therapeutic responses to alendronate in both postmenopausal and senile (old age) osteoporosis models. Last, we performed exome sequencing on patients taking N-BPs that suffered ONJ or an AFF. ATRAID is one of three genes that contain rare nonsynonymous coding variants in patients with ONJ or an AFF that is also differentially expressed in poor outcome groups of patients treated with N-BPs. We functionally validated this patient variation in ATRAID as conferring cellular hypersensitivity to N-BPs. Our work adds key insight into the mechanistic action of N-BPs and the processes that might underlie differential responsiveness to N-BPs in people.

Finding a Balance: Reconciling the Needs of the Institution, Patient, and Genetic Counselor for Optimal Resource Utilization.

The current practice of cancer genetic counseling is undergoing widespread change and scrutiny. While there are clinical resources for genetic counselors (GCs) regarding the delivery of cancer genetic services, there is limited literature regarding effective management of a genetic counseling clinical program. We have developed administrative tools to manage a large team of GCs at a single academic medical center over a period of increasing demand for genetics services, with the initial aim of decreasing wait time for urgent genetic counseling visits. Here, we describe the three main elements of the clinical operations: Balancing patient volume between GCs, scheduling tracks for both routine and urgent appointments, and a team of triaging GCs to ensure appropriate patient referrals. For each of these elements, we describe how they have been modified over time and present data to support the utility of these strategies. The preliminary evidence offered here suggests that these tools allow for an equitable distribution of patient volume between team members, as well as the timely and accurate scheduling of urgent patients. As a result of the experiences presented here, other genetic counseling programs grappling with similar issues should be aware that it is possible to shift clinical operations to serve certain patient populations in a more timely fashion while keeping both providers and GC staff satisfied.

Universal screening of both endometrial and colon cancers increases the detection of Lynch syndrome.

BACKGROUND: Lynch syndrome (LS) is the most common hereditary cause of colorectal cancer (CRC) and endometrial cancer (EC). Screening of all CRCs for LS is currently recommended, but screening of ECs is inconsistent. The objective of this study was to determine the added value of screening both CRC and EC tumors in the same population. METHODS: A prospective, immunohistochemistry (IHC)-based screening program for all patients with newly diagnosed CRCs and ECs was initiated in 2011 and 2013, respectively, at 2 centers (primary and tertiary). Genetic testing was recommended for those who had tumors with absent mutS homolog 2 (MSH2), MSH6, or postmeiotoic segregation increased 2 (PMS2) expression and for those who had tumors with absent mutL homolog 1 (MLH1) expression and no v-Raf murine sarcoma viral oncogene homolog B (BRAF) mutation or MLH1 promoter methylation. Amsterdam II criteria, revised Bethesda criteria, and scores from prediction models for gene mutations (the PREMM1,2,6 and PREMM5 prediction models) were ascertained in patients with LS. RESULTS: In total, 1290 patients with CRC and 484 with EC were screened for LS, and genetic testing was recommended for 137 patients (10.6%) and 32 patients (6.6%), respectively (P = .01). LS was identified in 16 patients (1.2%) with CRC and in 8 patients (1.7%) with EC. Among patients for whom genetic testing was recommended, the LS diagnosis rate was higher among those with EC (25.0% vs 11.7%, P = .052). The Amsterdam II criteria, revised Bethesda criteria, and both PREMM calculators would have missed 62.5%, 50.0%, and 12.5% of the identified patients with LS, respectively. CONCLUSIONS: Expanding a universal screening program for LS to include patients who had EC identified 50% more patients with LS, and many of these patients would have been missed by risk assessment tools (including PREMM5 ). Universal screening programs for LS should include both CRC and EC. Cancer 2018. © 2018 American Cancer Society.

A Rapid Systematic Review of Outcomes Studies in Genetic Counseling.

As healthcare reimbursement is increasingly tied to value-of-service, it is critical for the genetic counselor (GC) profession to demonstrate the value added by GCs through outcomes research. We conducted a rapid systematic literature review to identify outcomes of genetic counseling. Web of Science (including PubMed) and CINAHL databases were systematically searched to identify articles meeting the following criteria: 1) measures were assessed before and after genetic counseling (pre-post design) or comparisons were made between a GC group vs. a non-GC group (comparative cohort design); 2) genetic counseling outcomes could be assessed independently of genetic testing outcomes, and 3) genetic counseling was conducted by masters-level genetic counselors, or non-physician providers. Twenty-three papers met the inclusion criteria. The majority of studies were in the cancer genetic setting and the most commonly measured outcomes included knowledge, anxiety or distress, satisfaction, perceived risk, genetic testing (intentions or receipt), health behaviors, and decisional conflict. Results suggest that genetic counseling can lead to increased knowledge, perceived personal control, positive health behaviors, and improved risk perception accuracy as well as decreases in anxiety, cancer-related worry, and decisional conflict. However, further studies are needed to evaluate a wider array of outcomes in more diverse genetic counseling settings.

A tailored approach to BRAF and MLH1 methylation testing in a universal screening program for Lynch syndrome.

To determine the correlation between BRAF genotype and MLH1 promoter methylation in a screening program for Lynch syndrome (LS), a universal screening program for LS was established in two medical centers. Tumors with abnormal MLH1 staining were evaluated for both BRAF V600E genotype and MLH1 promoter methylation. Tumors positive for both were considered sporadic, and genetic testing was recommended for all others. A total 1011 colorectal cancer cases were screened for Lynch syndrome, and 148 (14.6%) exhibited absent MLH1 immunostaining. Both BRAF and MLH1 methylation testing were completed in 126 cases. Concordant results (both positive or both negative) were obtained in 86 (68.3%) and 16 (12.7%) cases, respectively, with 81% concordance overall. The positive and negative predictive values for a BRAF mutation in predicting MLH1 promoter methylation were 98.9% and 41%, respectively, and the negative predictive value fell to 15% in patients ≥70 years old. Using BRAF genotyping as a sole test to evaluate cases with absent MLH1 staining would have increased referral rates for genetic testing by 2.3-fold compared with MLH1 methylation testing alone (31% vs 13.5%, respectively, P<0.01). However, a hybrid approach that reserves MLH1 methylation testing for BRAF wild-type cases only would significantly decrease the number of methylation assays performed and reduce the referral rate for genetic testing to 12.7%. A BRAF mutation has an excellent positive predictive value but poor negative predictive value in predicting MLH1 promoter methylation. A hybrid use of these tests may reduce the number of low-risk patients referred to genetic counseling and facilitate wider implementation of Lynch syndrome screening programs.

Perceptions of Cancer Risk, Cause, and Needs in Participants from Low Socioeconomic Background at Risk for Hereditary Cancer.

The purpose of this study was to describe perceptions of cancer risk, cause, and needs in participants from a low socioeconomic background at risk for hereditary cancer. We surveyed 307 individuals with the Cancer Awareness and Needs survey and received 128 responses (41.6% response rate). Family history, genetics, and tobacco use were selected most frequently as a cause of cancer; 36% (n = 46) selected fate and/or God's will. A total of 87.5% (n = 112) understood that having a close family member with breast cancer could increase personal risk; however responses were varied when asked if this was related to risk for other cancers. Most participants had undergone cancer screening, half reported undergoing breast magnetic resonance imaging, which was associated with personal (p < 0.01) and family cancer history (p = 0.03). An additional 76.6% (n = 98) felt informed about cancer screening and most received information from health care providers and family or friends. Ensuring that patients and clinicians are educated about hereditary cancer risk, detection, and prevention should be priorities for future research.

Pathologic Findings in Prophylactic and Nonprophylactic Hysterectomy Specimens of Patients With Lynch Syndrome.

Women with Lynch syndrome (LS) have a high risk of developing endometrial carcinoma (EC) and, less frequently, ovarian carcinoma. As EC not uncommonly is the first malignancy, prophylactic hysterectomy (PH) has been increasingly implemented. In this study, we report the clinicopathologic features of a series of 70 LS patients who underwent either PH (n=39) or nonprophylactic hysterectomy (NPH) (n=31) at 3 tertiary referral centers. Among the 39 patients with PH, 2 had endometrial tumors seen grossly, whereas 37 showed no macroscopic lesions. Total inclusion of the endometrium was performed in 24/39 (61.5%). Abnormal histologic findings were identified in 9/39 (23.1%) PHs: 3 endometrial endometrioid carcinomas (EECs), including the 2 macroscopic and 1 microscopic (0.6 cm), and 4 atypical and 6 nonatypical hyperplasias. NPH included those performed for endometrial and ovarian cancer treatment. Tumor sampling followed standard protocols. ECs comprised 26 EECs and 1 clear cell carcinoma, with a median size of 3.7 cm. Hyperplasia was observed in 10 (33.3%) as background in EC, in 4 showing atypia. Eight (29.6%) tumors were centered in the lower uterine segment (all EECs). EECs were predominantly well differentiated (53.8%) and FIGO stage I (77.8%). A papillary architecture was common (51.9%) and associated with microcystic elongated and fragmented foci in 4. Mucinous differentiation was observed in 25.9% of endometrial tumors, typically representing <10%. Most endometrial tumors (81.5%) showed tumor-infiltrating lymphocyte counts ≥42/10 high-power fields. Four tumors showed extensive necrosis. Eight patients had ovarian tumors (4 synchronous), including 2 endometrioid carcinomas, 2 clear cell carcinomas, 1 borderline clear cell adenofibroma, 1 Müllerian carcinoma of mixed cell types, 1 primitive neuroectodermal tumor, and 1 metastatic melanoma. Total inclusion of the endometrium should be done in all LS patients' surgical specimens without macroscopic lesions as some of these patients harbor preneoplastic or neoplastic conditions treatable at an early stage. The phenotype of LS-associated endometrial and ovarian tumors is variable and frequently includes features not commonly observed in sporadic cancers, but in our experience carcinomas were in general low grade and low stage.

Clinical Actionability of Multigene Panel Testing for Hereditary Breast and Ovarian Cancer Risk Assessment.

IMPORTANCE: The practice of genetic testing for hereditary breast and/or ovarian cancer (HBOC) is rapidly evolving owing to the recent introduction of multigene panels. While these tests may identify 40% to 50% more individuals with hereditary cancer gene mutations than does testing for BRCA1/2 alone, whether finding such mutations will alter clinical management is unknown. OBJECTIVE: To define the potential clinical effect of multigene panel testing for HBOC in a clinically representative cohort. DESIGN, SETTING, AND PARTICIPANTS: Observational study of patients seen between 2001 and 2014 in 3 large academic medical centers. We prospectively enrolled 1046 individuals who were appropriate candidates for HBOC evaluation and who lacked BRCA1/2 mutations. INTERVENTIONS: We carried out multigene panel testing on all participants, then determined the clinical actionability, if any, of finding non-BRCA1/2 mutations in these and additional comparable individuals. MAIN OUTCOMES AND MEASURES: We evaluated the likelihood of (1) a posttest management change and (2) an indication for additional familial testing, considering gene-specific consensus management guidelines, gene-associated cancer risks, and personal and family history. RESULTS: Among 1046 study participants, 40 BRCA1/2-negative patients (3.8%; 95% CI, 2.8%-5.2%) harbored deleterious mutations, most commonly in moderate-risk breast and ovarian cancer genes (CHEK2, ATM, and PALB2) and Lynch syndrome genes. Among these and an additional 23 mutation-positive individuals enrolled from our clinics, most of the mutations (92%) were consistent with the spectrum of cancer(s) observed in the patient or family, suggesting that these results are clinically significant. Among all 63 mutation-positive patients, additional disease-specific screening and/or prevention measures beyond those based on personal and family history alone would be considered for most (33 [52%] of 63; 95% CI, 40.3%-64.2%). Furthermore, additional familial testing would be considered for those with first-degree relatives (42 [72%] of 58; 95% CI, 59.8%-82.2%) based on potential management changes for mutation-positive relatives. This clinical effect was not restricted to a few of the tested genes because most identified genes could change clinical management for some patients. CONCLUSIONS AND RELEVANCE: In a clinically representative cohort, multigene panel testing for HBOC risk assessment yielded findings likely to change clinical management for substantially more patients than does BRCA1/2 testing alone. Multigene testing in this setting is likely to alter near-term cancer risk assessment and management recommendations for mutation-affected individuals across a broad spectrum of cancer predisposition genes.

Cowden syndrome and the PTEN hamartoma tumor syndrome: systematic review and revised diagnostic criteria.

BACKGROUND: PTEN hamartoma tumor syndrome (PHTS) refers to a spectrum of disorders caused by mutations in the phosphatase and tensin homolog (PTEN) gene. Diagnostic criteria for Cowden syndrome, the principal PTEN-related disorder, were first established in 1996 before the identification of the PTEN gene and the ability to molecularly confirm a clinical diagnosis. These consortium criteria were based on clinical experience and case reports in the existing literature, with their inherent selection biases. Although it was initially reported that approximately 80% of patients with Cowden syndrome had an identifiable germline PTEN mutation, more recent work has shown these diagnostic criteria to be far less specific. In addition, increasing evidence has documented the association of a broader spectrum of clinical features with PTEN mutations. Our goal was to develop revised, evidence-based diagnostic criteria and to include features of the broader spectrum of PTEN-related clinical syndromes. METHODS: We performed a systematic search and review of the medical literature related to clinical features reported in individuals with a PTEN mutation and/or a related clinical diagnosis. RESULTS: We found no sufficient evidence to support inclusion of benign breast disease, uterine fibroids, or genitourinary malformations as diagnostic criteria. There was evidence to include autism spectrum disorders, colon cancer, esophageal glycogenic acanthosis, penile macules, renal cell carcinoma, testicular lipomatosis, and vascular anomalies. CONCLUSIONS: We propose revised, evidence-based criteria covering the spectrum of PTEN-related clinical disorders. Additional research on clinical features associated with PTEN mutations is warranted.

Impact of genetic testing on endometrial cancer risk-reducing practices in women at risk for Lynch syndrome.

OBJECTIVE: Due to the increased lifetime risk of endometrial cancer (EC), guidelines recommend that women with Lynch syndrome (LS) age ≥ 35 undergo annual EC surveillance or prophylactic hysterectomy (PH). The aim of this study was to examine the uptake of these risk-reducing strategies. METHODS: The study population included women meeting clinical criteria for genetic evaluation for LS. Data on cancer risk-reducing behaviors were collected from subjects enrolled in two distinct studies: (1) a multicenter cross-sectional study involving completion of a one-time questionnaire, or (2) a single-center longitudinal study in which subjects completed questionnaires before and after undergoing genetic testing. The main outcome was uptake of EC risk-reducing practices. RESULTS: In the cross-sectional cohort, 58/77 (75%) women at risk for LS-associated EC reported engaging in EC risk-reduction. Personal history of genetic testing was associated with uptake of EC surveillance or PH (OR 17.1; 95% CI 4.1-70.9). Prior to genetic testing for LS, 26/40 (65%) women in the longitudinal cohort reported engaging in EC risk-reduction. At one-year follow-up, 16/16 (100%) mismatch repair (MMR) gene mutation carriers were adherent to guidelines for EC risk-reduction, 9 (56%) of whom had undergone PH. By three-year follow-up, 11/16 (69%) MMR mutation carriers had undergone PH. Among women with negative or uninformative genetic test results, none underwent PH after testing. CONCLUSIONS: Genetic testing for LS is strongly associated with uptake of EC risk-reducing practices. Women found to have LS in this study underwent prophylactic gynecologic surgery at rates comparable to those published for BRCA1/2 mutation carriers.