Genetic testing and referral patterns of non-BRCA mutation carriers at increased or uncertain risk of ovarian cancer.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 1585-1585
Author(s):  
Sarah S. Lee ◽  
Katherine Baumann ◽  
Bhoomi Bhuptani ◽  
Sarah Turecamo ◽  
Julia Anne Smith ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Genetic Testing ◽  
Brca Mutation ◽  
Genetic Counselor ◽  
Brca Mutations ◽  
Chi Square ◽  
Increased Risk ◽  
Uncertain Significance ◽  
Brca Mutation Carriers ◽  
Icd 10

1585 Background: While the management of BRCA1/2 is clear, management of non-BRCA mutations with increased risk or uncertain risk of ovarian cancer (OC) is not well established. Previously, we reported that referral to a gynecologic oncologist (GO) resulted in a 30-fold increased uptake of risk reducing surgery (RRS). We aimed to identify trends in genetic testing (GT) and referral to a GO of patients (pts) with such mutations. Methods: In this retrospective cohort study at 3 satellite sites within 1 institution from 2014 to 2018, pts were identified by ICD-10 codes Z15.01, Z15.02, Z15.09, Z15.89, C50.919, Q99.8, and C54.1. Pts with mutations with increased risk of OC ( MLH1, MSH2/6, PMS2, EPCAM (LS genes) , RAD51C/D, BRIP1, STK11) and uncertain risk of OC ( PALB2, ATM, BARD1, NBN) were included; BRCA1/2 and variants of uncertain significance were excluded . Outcomes of interest were patterns of GT and referral to a GO. Chi square and logistic regression were used with p < 0.05. Results: Of 20,000 pts with above ICD-10 codes, 240 pts had genes of interest. Mutations in increased risk of OC included: LS genes, 131; BRIP1, 14; RAD51D, 8; RAD51C, 5; STK11, 1. Mutations associated with uncertain risk of OC were: ATM, 43; PALB2, 23; NBN, 10; BARD1, 5. Pts with known mutations prior establishing care at our institution (N = 69) were less likely to be referred to a GO (22% vs 78%, p = 0.015). Pts with LS genes were more likely to be referred to a GO (52% vs. 25%, p < 0.001), to be tested by a GC (52% vs 25%, p < 0.001), and to be tested for family history (FH) of known mutation (69% vs 30%, p < 0.001). Provider performing GT included: genetic counselor (GC), 66 (28%); medical oncologist, 44 (18%); general obstetrician-gynecologist, 44 (18%); breast surgeon, 6 (3%), and primary care provider, 5 (2%). Of 66 pts tested by a GC, 46 (70%) were referred to GO, vs 48/105 (45%) pts who underwent GT by non-GC (p = 0.001). Reasons for GT among pts were: FH of cancer, 113 (47%); personal history of cancer, 56 (23%); known FH of a mutation, 49 (20%); and unknown indication, 22 (9%). When controlling for age, parity, race, insurance, GT provider, and reasons for GT, mutations with increased risk of OC were associated with referral to a GO (OR 3.55, 95% CI 1.88-6.72), along with pts who were tested by a GC (OR 2.65, 95% CI 1.27-5.51). Conclusions: Only ~30% of pts underwent GT by a GC, which was associated with increased referral to a GO. LS genes are better known and were associated with higher uptake of GO referral. Education of OC risks of these newer mutations among providers performing GT may increase referral to a GO and uptake of RRS.

scholarly journals Tailoring Ovarian Cancer Treatment: Implications of BRCA1/2 Mutations

Cancers ◽  
2019 ◽  
Vol 11 (3) ◽  
pp. 416 ◽  
Author(s):  
Ainhoa Madariaga ◽  
Stephanie Lheureux ◽  
Amit Oza
Keyword(s):  
Ovarian Cancer ◽  
Brca Mutation ◽  
Repair Process ◽  
Resistance Mechanisms ◽  
Tumour Suppressor Genes ◽  
Brca1 And Brca2 ◽  
Brca Mutations ◽  
Damage Repair ◽  
Brca Mutation Carriers ◽  
Drug Efflux Pumps

High grade serous ovarian cancer (HGSOC) is the most common epithelial ovarian cancer, harbouring more than 20% germline or somatic mutations in the tumour suppressor genes BRCA1 and BRCA2. These genes are involved in both DNA damage repair process via homologous recombination (HR) and transcriptional regulation. BRCA mutation confers distinct characteristics, including an increased response to DNA-damaging agents, such us platinum chemotherapy and poly-ADP ribose polymerase inhibitors (PARPi). However, several mechanisms of resistance to these agents have been described, including increased HR capacity through reverse BRCA mutations, non-homologous end-joint (NHEJ) repair alterations and drug efflux pumps. Current treatments of ovarian cancer including surgery, chemotherapy, targeted treatment and maintenance strategies, as well as resistance mechanisms will be reviewed, focusing on future trends with respect to BRCA mutation carriers.

Comparison of risk-reducing surgery in women with BRCA and non-BRCA ovarian cancer susceptibility genes.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 1547-1547
Author(s):  
Zachary Phillip Schwartz ◽  
Mae Zakhour ◽  
Andrew John Li ◽  
Christine S. Walsh ◽  
Bj Rimel ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Susceptibility ◽  
Brca Mutation ◽  
Susceptibility Genes ◽  
Brca Mutations ◽  
Cancer Susceptibility Genes ◽  
Mutation Carriers ◽  
Brca Mutation Carriers ◽  
History Of ◽  
Risk Reducing

1547 Background: Risk reducing gynecologic surgery (RRSO) is standard of care for women with BRCA mutations. The optimal management for women with non-BRCA ovarian cancer susceptibility mutations remains unclear. We sought to characterize the practice patterns for these women at our two institutions. Methods: Women with germline ovarian cancer susceptibility genes who had a RRSO were identified from 1/2000-1/2019 in an IRB approved study. All patients were asymptomatic with no suspicion for malignancy at time of RRSO. Clinico-pathologic characteristics were extracted from the medical records. Continuous variables were analyzed with Kruskal-Wallis and categorical variables analyzed with chi square and t-tests. Results: 152 BRCA1, 95 BRCA2, and 63 Non-BRCA mutation carriers were identified—50 Lynch (22 MLH1, 13 MSH2, 13 MSH6, 2 PMS2) and 13 Other (6 BRIP1, 2 RAD51C, 5 RAD51D). There was no difference between age at testing, age at RRSO, and interval between testing and RRSO between groups. Genetic counseling was higher in Non-BRCA patients. Family history of ovarian cancer was more common in women with BRCA1 and Other germline mutations compared to BRCA2 and Lynch. Family and personal history of breast cancer was high in all groups except Lynch carriers. Prophylactic mastectomy was seen mostly in BRCA mutation carriers. Concomitant hysterectomy was performed in the majority of women (BRCA1 59%, BRCA2 57%, and Other 62%), with the highest frequency in Lynch carriers (86%, p<.01). Occult cancer was only seen in BRCA mutation carriers: BRCA1 (7%), BRCA2 (2%), Lynch (0%), Other (0%). Conclusions: In this cohort, women with Non-BRCA mutations are managed similarly to women with BRCA mutations. We observed no occult cancers in Non-BRCA patients. The optimal role of surgery as a risk reducing strategy in this group requires further study. [Table: see text]

scholarly journals Biological Role and Clinical Implications of microRNAs in BRCA Mutation Carriers

2021 ◽  
Vol 11 ◽  
Author(s):  
Chiara Tommasi ◽  
Benedetta Pellegrino ◽  
Daniela Boggiani ◽  
Angelica Sikokis ◽  
Maria Michiara ◽  
...  
Keyword(s):  
Brca Mutation ◽  
Scientific Evidence ◽  
Clinical Implications ◽  
Brca Mutations ◽  
Small Noncoding Rnas ◽  
Mutation Carriers ◽  
Increased Risk ◽  
Modifiable Factors ◽  
Brca Mutation Carriers

Women with pathogenic germline mutations in BRCA1 and BRCA2 genes have an increased risk to develop breast and ovarian cancer. There is, however, a high interpersonal variability in the modality and timing of tumor onset in those subjects, thus suggesting a potential role of other individual’s genetic, epigenetic, and environmental risk factors in modulating the penetrance of BRCA mutations. MicroRNAs (miRNAs) are small noncoding RNAs that can modulate the expression of several genes involved in cancer initiation and progression. MiRNAs are dysregulated at all stages of breast cancer and although they are accessible and evaluable, a standardized method for miRNA assessment is needed to ensure comparable data analysis and accuracy of results. The aim of this review was to highlight the role of miRNAs as potential biological markers for BRCA mutation carriers. In particular, biological and clinical implications of a link between lifestyle and nutritional modifiable factors, miRNA expression and germline BRCA1 and BRCA2 mutations are discussed with the knowledge of the best available scientific evidence.

Adherence to referral guidelines

2019 ◽  
Vol 24 (1) ◽  
pp. 6-18 ◽  
Author(s):  
Michel Lu ◽  
Allan D. Spigelman
Keyword(s):  
Genetic Testing ◽  
Brca Mutation ◽  
Evidence Based ◽  
Brca Mutations ◽  
Content Type ◽  
Gene Testing ◽  
South Wales ◽  
Brca Mutation Carriers ◽  
Evidence Based Guidelines ◽  
Referral Practice

Purpose A significant subset of patients (12 per cent) with triple negative breast cancer (TNBC) is BRCA mutation carriers, which can be identified through genetic testing. The purpose of this paper is to evaluate the referral practice for TNBC patients with reference to New South Wales (NSW) referral guidelines at the time of diagnosis and to assess the effectiveness of such guidelines in identifying BRCA mutations. Robust health governance requires monitoring of adherence to evidence-based guidelines such as those that underpin referral for cancer genetic testing in this clinical scenario. Design/methodology/approach The authors conducted a retrospective clinical audit of identified TNBC patients at St Vincent’s Hospital (SVH) between 2006 and 2016 in NSW, comparing referral practice to guidelines extant at the time of diagnosis. Family history was considered for age guideline-inappropriate referrals to SVH while the results of BRCA gene testing were assessed for all referred. Findings Overall, of the 17 patients eligible for referral based on the age criterion, 10 (58.5 per cent) were referred appropriately; however, there were substantial improvements from 2012 with 100 per cent referred. Of note, 12 (33.4 per cent) of 36 patients referred to SVH were referred outside of guidelines, pointing to other reasons for referral, such as patient age (OR 0.945; 95% CI 0.914–0.978) and calendar year (OR: 1.332; 95% CI: 1.127–1.575) at TNBC diagnosis. Referral guidelines captured 66.67 per cent of identified deleterious BRCA mutations in those tested. Originality/value Substantial under-referral of guideline-eligible patients was identified, with evidence-based guidelines effective in identifying high-risk individuals for BRCA mutation testing. There was, however, a substantial proportion of guideline-inappropriate referrals.

scholarly journals Insights into BRCA Cancer Predisposition from Integrated Germline and Somatic Analyses in 7632 Cancers

2019 ◽  
Vol 3 (2) ◽  
Author(s):  
Shawn Yost ◽  
Elise Ruark ◽  
Ludmil B Alexandrov ◽  
Nazneen Rahman
Keyword(s):  
Ovarian Cancer ◽  
Statistical Tests ◽  
Brca Mutation ◽  
Pathogenic Mutation ◽  
Brca Mutations ◽  
Variant Of Uncertain Significance ◽  
Allele Loss ◽  
Ovarian Cancers ◽  
Pathogenic Mutations ◽  
Uncertain Significance

Abstract Background It is often assumed any cancer in a germline BRCA1 or BRCA2 (collectively termed BRCA) mutation carrier was caused by that mutation. It is also often assumed the occurrence of breast or ovarian cancer in an individual with a variant of uncertain significance (VUS) suggests the VUS is pathogenic. These assumptions have profound management implications for cancer patients and healthy individuals. Methods We compared the frequency of BRCA mutations, allele loss, and Signature 3 in 7632 individuals with 28 cancers and 1000 population controls. Because only increased frequency was the focus of the study, all statistical tests were one-sided. Results Individuals with breast or ovarian cancer had increased germline BRCA pathogenic mutation frequencies compared to controls (P = 1.0x10−10 and P = 1.4x10−34, respectively). There was no increase in other cancer types. Wild-type allele loss and Signature 3 were statistically significantly higher in breast and ovarian cancers with BRCA mutations compared with other cancers with BRCA mutations (P = 5.1x10−10 and P = 3.7x10−9) and cancers without BRCA mutations (P = 2.8x10−53 and P = 1.0x10−134). There was no difference between non-breast and non-ovarian cancers with BRCA mutations and cancers without BRCA mutations. Allele loss and Signature 3 were statistically significantly higher in breast and ovarian cancers in individuals with BRCA pathogenic mutations compared to those with VUS (P = 3.8x10−17 and P = 1.6x10−8) or benign variants (P = 1.2x10−28 and P = 2.2x10−10). There was no difference between individuals with BRCA VUS and those with benign variants. Conclusions These data show that non-breast and non-ovarian cancers in individuals with germline BRCA pathogenic mutations are often not causally related to the mutation and that BRCA VUS are highly unlikely to be pathogenic. These results should reduce inappropriate management of germline BRCA information.

Practical assessment of psychosocial concerns associated with genetic testing in ovarian cancer patients using the MICRA questionnaire.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 9569-9569
Author(s):  
Merete Bjørnslett ◽  
Alv A. Dahl ◽  
Øystein Sørebø ◽  
Anne Dørum
Keyword(s):  
Ovarian Cancer ◽  
Genetic Testing ◽  
Cancer Patients ◽  
Brca Mutation ◽  
Mutation Carriers ◽  
Brca Mutation Carriers ◽  
History Of ◽  
Positive Experiences ◽  
Explained Variance

9569 Background: Ten to 15% of ovarian cancer patients are BRCA mutation carriers. By offering genetic testing, families at risk and healthy female mutation carriers will be identified and offered clinical follow-up. The MICRA questionnaire was developed as a brief, practical, and targeted assessment of concerns and psychosocial issues associated with genetic testing. This study evaluates the practical and psychometric properties of the MICRA (Norwegian translation) in tested ovarian cancer patient. Methods: Since 2002, ovarian cancer patients at Oslo University Hospital, Norwegian Radium Hospital are offered genetic counseling and testing. By the end of 2009, 1,032 were included. The 530 (51%) patients still alive, were mailed the MICRA and three other instruments relevant for mental distress. 354 (67%) patients responded. Among them 9% were BRCA mutation carriers, 7% had a personal history of breast cancer, 29% had a family history of breast and/or ovarian cancer, and 55% had no such family history. Results: In the BRCA mutation carrier group, the total MICRA score and its subscale scores of distress, uncertainty, and positive experiences were all significantly higher than in the other groups. Confirmatory factor analyses of the three subscales of MICRA showed inadequate fit indices, while a four factors solution including the new factor of Support from family (items #18 and #19), showed adequate fit. The Positive Experiences subscale showed a maximum of 4% explained variance in relation to the Hospital Anxiety and Depression Scale total score, the Impact of Event Avoidance and Intrusion scores, and the Eysenck’s Neuroticism score. The subscales of Distress and Uncertainty showed maximum 12% and 41% explained variance, respectively, while the total MICRA score showed 22% explained variance. Conclusions: Our study supports the feasibility of the MICRA in ovarian cancer patients. Frail women may be identified for closer follow-up by using MICRA. Discrimant, content and construct validities of the MICRA were supported, while the factor structure still is open to further investigation.

Survival in advanced-stage ovarian cancer patients with non-Ashkenazi Jewish BRCA mutations

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 5514-5514
Author(s):  
R. A. Lacour ◽  
S. N. Westin ◽  
M. S. Daniels ◽  
M. R. Milam ◽  
C. C. Sun ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Overall Survival ◽  
Cancer Patients ◽  
Initial Treatment ◽  
Brca Mutation ◽  
Complete Response ◽  
Advanced Stage ◽  
Ashkenazi Jewish ◽  
Brca Mutations ◽  
Brca Mutation Carriers

5514 Background: Previous studies have shown a survival advantage in ovarian cancer patients with Ashkenazi-Jewish BRCA founder mutations compared to sporadic ovarian cancer patients. The purpose of this study is to determine if this association exists in ovarian cancer patients with non- Ashkenazi Jewish (non-AJ) BRCA1 or BRCA2 mutations. Methods: Patients with stage III or IV ovarian, fallopian tube, or primary peritoneal cancer and a BRCA1 or BRCA2 mutation, seen for genetic testing between January 1996 and October 2006, were identified from the institutional and genetics databases. Medical records were reviewed for clinical factors including response to initial chemotherapy. Response is defined as no clinical evidence of disease with normalization of serum CA-125 and no radiographic evidence of disease or a negative second-look surgery. Patients with sporadic ovarian cancer, without a family history of breast or ovarian cancer, were compared to similar cases, matched by age, stage, and year of diagnosis. Progression-free and overall survival were calculated by the method of Kaplan-Meier. Chi-square tests and univariate logistic regression were also used in the data analysis. Results: Thirty-nine advanced-stage ovarian cancer patients with non-AJ BRCA mutations and 47 matched, advanced-stage sporadic ovarian cancer patients have been analyzed. Compared to patients with sporadic ovarian cancer, non-AJ BRCA mutation carriers had a longer progression-free survival (PFS, 32.4 mos. vs. 22.1 mos., p = 0.0303) and overall survival (OS, 101.4 mos. vs. 51.3 mos., p < 0.001). Similarly, 72% of the non-AJ BRCA mutation carriers had a complete response to initial treatment, compared to 45% of the sporadic ovarian cancer patients (p = 0.01). The odds of complete response to initial treatment were 3.2 times greater in the non-AJ BRCA group than in the sporadic group (OR 3.2; 95% CI 1.27 - 8.15). Conclusions: This study demonstrates a significant survival advantage in advanced-stage ovarian cancer patients with non-AJ BRCA mutations when compared to similar patients with sporadic ovarian cancer. Response to initial treatment appears to impact this improved survival. No significant financial relationships to disclose.

American BRCA outcomes and utilization of testing (ABOUT) study.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 1608-1608
Author(s):  
Rebecca Sutphen ◽  
Joseph E. Bauer ◽  
Katherine S. Virgo ◽  
Carolina Casares ◽  
Gregg Walker ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Genetic Testing ◽  
Community Setting ◽  
Healthcare Services ◽  
High Risk Group ◽  
Breast And Ovarian Cancer ◽  
Chi Square ◽  
Services Delivery ◽  
Increased Risk ◽  
The U.S

1608 Background: An estimated 100,000 individuals currently undergo genetic testing for hereditary susceptibility to breast and ovarian cancer annually in the U.S., yet little is known about their characteristics, testing experience or outcomes. Research in this high-risk group has been limited to patients recruited at academic medical centers where case ascertainment, health services delivery, decision-making and, quite likely, outcomes are different from those in the community setting where the majority of individuals currently receive healthcare services. Methods: Eligible subjects include 10,000 consecutive individuals requesting BRCA testing through the nation’s third-largest health insurer, Aetna, beginning in December, 2011. De-identified data are analyzed from each test request form submitted by the ordering provider. Each eligible subject is mailed a study packet inviting them to complete a questionnaire (by mail, online or telephone) designed to investigate informational and healthcare services, test results, knowledge, risk perception and medical intentions. Results: Of 442 subjects contacted during the first two weeks of accrual, 143 (32%) have completed the questionnaire to date. Similar to Aetna member demographics, 7% are African-American and 7% report Hispanic ethnicity. Based on Chi-Square tests, there were no differences between respondents and non-respondents with regard to age (51% under age 50), race, ethnicity or personal history of cancer (58%). Among respondents, deleterious mutations were identified in 8%. Testing for a known familial mutation was performed in 8%. Among women with breast cancer, 13% were undergoing testing prior to initial surgical treatment. Updated results from 3000 eligible subjects will be presented. Conclusions: This innovative, academic-industry collaboration enables an unprecedented investigation of significant issues surrounding individuals at increased risk for hereditary breast and ovarian cancer and undergoing genetic testing in the U.S. The results will guide the development and dissemination of more targeted decision-support tools and strategies to improve medical outcomes for such individuals.

scholarly journals Reliability of Tumor Testing Compared to Germline Testing for Detecting BRCA1 and BRCA2 Mutations in Patients with Epithelial Ovarian Cancer

2021 ◽  
Vol 11 (7) ◽  
pp. 593
Author(s):  
Christine Bekos ◽  
Christoph Grimm ◽  
Marlene Kranawetter ◽  
Stephan Polterauer ◽  
Felicitas Oberndorfer ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Brca Mutation ◽  
Treatment Decision ◽  
Concordance Rate ◽  
Brca1 And Brca2 ◽  
Brca Mutations ◽  
Uncertain Significance ◽  
Brca1 And Brca2 Mutations ◽  
Germline Testing

Background: BRCA 1/2 mutation status has become one of the most important parameters for treatment decision in patients with epithelial ovarian cancer (EOC). The aim of this study was to compare tumor DNA with blood DNA sequencing to evaluate the reliability of BRCA tumor testing results. Methods: Patients who were treated for EOC between 2003 and 2019 at the Medical University of Vienna and underwent both germline (gBRCA) and tumor (tBRCA) testing for BRCA mutations were identified. We calculated the concordance rate and further analyzed discordant cases. Results: Out of 140 patients with EOC, gBRCA mutation was found in 47 (33.6%) and tBRCA mutation in 53 (37.9%) patients. Tumor testing identified an additional 9/140 (6.4%) patients with somatic BRCA mutation and negative germline testing. The comparison of germline testing with tumor testing revealed a concordance rate of 93.5% and a negative predictive value of tumor testing of 96.0%. After BRCA variants of uncertain significance were included in the analysis, concordance rate decreased to 90.9%. Conclusion: Tumor testing identified the majority of pathogenic germline BRCA mutations but missed three (2.1%) patients. In contrast, nine (6.4%) patients harboring a somatic BRCA mutation would have been missed by gBRCA testing only.

Sign in / Sign up

Export Citation Format

Share Document