scholarly journals FLABRA, frontline approach for BRCA testing in an ovarian cancer population: a Latin America epidemiologic study

2021 ◽  
Author(s):  
Gonzalo Giornelli ◽  
Dolores Gallardo ◽  
Roberto Hegg ◽  
Gonzalo Gomez Abuin ◽  
Maximo De La Vega ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Latin America ◽  
Genetic Counseling ◽  
Latin American ◽  
Treatment Plan ◽  
Epidemiologic Study ◽  
Brca Mutations ◽  
Clinical Trial Registration ◽  
Uncertain Significance ◽  
Management Approaches

Aim: FLABRA (NCT02984423) evaluated prevalence of BRCA mutations, genetic counseling and management approaches in patients with ovarian cancer in Latin America. Patients & methods: Patients with ovarian cancer from six Latin American countries were enrolled. Tumor samples were tested for BRCA mutations. In cases with BRCA mutations ( BRCA mut), blood samples were analyzed to determine germline versus somatic mutations. Medical records were reviewed for counseling approach and treatment plan. Results: From 472 patients enrolled, 406 samples yielded conclusive results: 282 were BRCA wild-type ( BRCA wt), 115 were  BRCA mut and nine were variants of uncertain significance. In total, 110/115 were tested for germline mutations (77 germline and 33 somatic). Conclusion: Tumor testing to identify mutations in BRCA1/2 in ovarian cancer can help optimize treatment choices, meaning fewer patients require germline testing and genetic counseling, a scant resource in Latin America. Clinical trial registration: NCT02984423 (https://ClinicalTrials.gov)

FLABRA, frontline approach for BRCA testing in ovarian cancer (OC) treatment naïve population: A Latin America (LA) epidemiologic study.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e17050-e17050
Author(s):  
Susana Beatriz Goncalves ◽  
Gonzalo Giornelli ◽  
Marcelo Horacio Pereira ◽  
Dolores Gallardo-Rincon ◽  
Maria Del Pilar Estevez-Diz
Keyword(s):  
Genetic Counseling ◽  
Latin American ◽  
Somatic Mutations ◽  
Significant Proportion ◽  
Epidemiologic Study ◽  
Parp Inhibitors ◽  
Brca Testing ◽  
Brca Mutations ◽  
Cross Sectional ◽  
Preliminary Results

e17050 Background: The majority of OC cases are sporadic, but it is estimated that in 17%, germline mutations in BRCA1 or BRCA2 genes can be identified. BRCA mutated OC has distinct clinical characteristics, increased sensitivity to platinum and non-platinum agents, and to DNA damage repair (DDR) targeting agents like PARP inhibitors. Additionally, somatic BRCA mutations could be identified in tumor tissue. The prevalence of germline BRCA mutations (gBRCAm) and somatic mutations (sBRCAm) has been not been characterized in Latin-american population, which is a paradigm of poly-ethnicity, where prevalence of germline, but especially somatic BRCA mutations in OC, has not been studied. Furthermore, tumor testing as first step may be a new option in BRCA testing algorithm that could avoid the necessity for double testing (gBRCA, then sBRCA testing), in case of gBRCAm negative result. Methods: FLABRA is a cross-sectional, multi-center, study designed to determine the prevalence of sBRCAm in newly diagnosed OC patients versus gBRCAm, and to describe different treatment approaches at front line in LA, as well as current OC genetic counselling. We enrolled 400 consecutive patients from 40 institutions in Argentina, Brazil, Colombia, Mexico, Peru and Panama, diagnosed with OC. Tumor blocks were tested for sBRCA (Myriad Tumor BRACAnalysis CDx™). In sBRCA positive patients, blood samples were analyzed to confirm if the mutation was germline or somatic in origin. In gBRCAm, genetic counseling was advised. Medical records were reviewed for data relevant to medical history, surgery results, treatment approach and genetic counseling. Results: We present the preliminary results with 291 patients already tested. For this first subset of patients, 85/291 (29%) had BRCA mutations identified in their tumors. Preliminary results confirm that starting with tumor testing enlarges the population eligible for PARP inhibitors, by identifying additional patients with somatic mutations only detectable in the tumor. Although preliminary, our data confirms the possibility of identifying additional patients with sBRCA mutations by testing in tumor, with a more cost-effective approach, avoiding a second round of gBRCA testing in patients with BRCA negative results in tumor. Conclusions: In this preliminary analysis we found that somatic BRCA mutations account for a significant proportion from total BRCA mutations within LA population studied.

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 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.

Impact of Clinical Genetics Attendance at a Gynecologic Oncology Tumor Board on Referrals for Genetic Counseling and BRCA Mutation Testing

2016 ◽  
Vol 26 (5) ◽  
pp. 892-897 ◽  
Author(s):  
Paul A. Cohen ◽  
Cassandra B. Nichols ◽  
Lyn Schofield ◽  
Steven Van Der Werf ◽  
Nicholas Pachter
Keyword(s):  
Ovarian Cancer ◽  
Genetic Counseling ◽  
Brca Mutation ◽  
Gynecologic Oncology ◽  
Mutation Testing ◽  
High Rate ◽  
Tumor Board ◽  
Clinical Genetics ◽  
Brca Mutations ◽  
Referral Rates

ObjectivesThe objectives of this work were to determine the proportion of eligible patients with ovarian cancer discussed at a gynecologic oncology tumor board who were referred for counseling and BRCA mutation testing; to compare referral rates before genetics attendance at the tumor board to referral rates after genetics attendance; and to ascertain the proportions of women with germline BRCA mutations.Materials and MethodsEligible cases were identified from the minutes of the weekly Western Australian gynecologic oncology tumor board from July 1, 2013 to June 30, 2015.Patients with ovarian cancer who met eligibility criteria for genetics referral were identified and checked against the records of the genetic services database to ascertain whether a referral was received. Outcomes including attendance for counseling and results of mutation testing were analyzed.ResultsTwo hundred sixty-one patients were eligible for referral during the 24-month study period. One hundred six patients (40.6%) were referred for counseling and germline mutation testing. Of the eligible patients, 26.7% were referred in the 12 months before genetics attendance at the tumor board compared to 51.7% of the eligible patients in the 12 months after genetics attendance (P ≤ 0.0001). Ninety-seven patients were offered BRCA mutation testing, and 73 underwent testing with 65 results reported to date. Twenty-two patients (33.8 %) tested positive for a germline BRCA mutation.ConclusionsPatients with ovarian cancer had a high rate of BRCA mutations. Attendance of a genetics service at a tumor board was associated with an improved rate of referral of patients for genetic counseling and BRCA mutation testing.

Olaparib maintenance monotherapy in platinum-sensitive, relapsed ovarian cancer without germline BRCA mutations: OPINION Phase IIIb study design

2019 ◽  
Vol 15 (32) ◽  
pp. 3651-3663
Author(s):  
Andres M Poveda ◽  
Richard Davidson ◽  
Christopher Blakeley ◽  
Alvin Milner
Keyword(s):  
Ovarian Cancer ◽  
Brca2 Mutation ◽  
Progression Free Survival ◽  
Open Label ◽  
Brca Mutations ◽  
Clinical Trial Registration ◽  
Free Survival ◽  
Platinum Sensitive ◽  
Platinum Based Chemotherapy ◽  
Phase Iiib

The poly(ADP-ribose) polymerase inhibitor olaparib (Lynparza™) is approved for maintenance treatment of platinum-sensitive relapsed ovarian cancer. OPINION is a single-arm, open-label, multicenter, Phase IIIb study to assess the efficacy and safety of olaparib tablet maintenance therapy in women with high-grade serous or endometrioid platinum-sensitive relapsed ovarian cancer without a germline BRCA1 or BRCA2 mutation. Eligible patients should have received ≥2 prior lines of platinum-based chemotherapy and be in complete or partial response following their most recent course or have no evidence of disease. Patients will receive olaparib tablets (300 mg twice daily) until disease progression, unacceptable toxicity or another discontinuation criterion. The primary end point is investigator-assessed progression-free survival; secondary end points include progression-free survival according to tumor homologous recombination deficiency status. Clinical trial registration: NCT03402841.

scholarly journals Traceback: A Proposed Framework to Increase Identification and Genetic Counseling of BRCA1 and BRCA2 Mutation Carriers Through Family-Based Outreach

2017 ◽  
Vol 35 (20) ◽  
pp. 2329-2337 ◽  
Author(s):  
Goli Samimi ◽  
Marcus Q. Bernardini ◽  
Lawrence C. Brody ◽  
Charlisse F. Caga-anan ◽  
Ian G. Campbell ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Genetic Counseling ◽  
Brca2 Mutation ◽  
Gynecologic Oncology ◽  
Cancer Control ◽  
Brca1 And Brca2 ◽  
Brca Mutations ◽  
Pilot Studies ◽  
Mutation Carriers ◽  
Family Based

In May 2016, the Division of Cancer Prevention and the Division of Cancer Control and Population Sciences, National Cancer Institute, convened a workshop to discuss a conceptual framework for identifying and genetically testing previously diagnosed but unreferred patients with ovarian cancer and other unrecognized BRCA1 or BRCA2 mutation carriers to improve the detection of families at risk for breast or ovarian cancer. The concept, designated Traceback, was prompted by the recognition that although BRCA1 and BRCA2 mutations are frequent in women with ovarian cancer, many such women have not been tested, especially if their diagnosis predated changes in testing guidelines. The failure to identify mutation carriers among probands represents a lost opportunity to prevent cancer in unsuspecting relatives through risk-reduction intervention in mutation carriers and to provide appropriate reassurances to noncarriers. The Traceback program could provide an important opportunity to reach families from racial, ethnic, and socioeconomic groups who historically have not sought or been offered genetic counseling and testing and thereby contribute to a reduction in health disparities in women with germline BRCA mutations. To achieve an interdisciplinary perspective, the workshop assembled international experts in genetics, medical and gynecologic oncology, clinical psychology, epidemiology, genomics, cost-effectiveness modeling, pathology, bioethics, and patient advocacy to identify factors to consider when undertaking a Traceback program. This report highlights the workshop deliberations with the goal of stimulating research and providing a framework for pilot studies to assess the feasibility and ethical and logistical considerations related to the development of best practices for implementation of Traceback studies.

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.

Migration vs. development? The case of poverty and inequality in Mexico

2012 ◽  
Vol 9 (1) ◽  
pp. 65-74 ◽  
Author(s):  
Agustín Escobar Latapi
Keyword(s):  
Latin America ◽  
International Migration ◽  
Latin American ◽  
Opportunity Cost ◽  
Inequality Index ◽  
Poverty And Inequality ◽  
And Migration

Although the migration – development nexus is widely recognized as a complex one, it is generally thought that there is a relationship between poverty and emigration, and that remittances lessen inequality. On the basis of Latin American and Mexican data, this chapter intends to show that for Mexico, the exchange of migrants for remittances is among the lowest in Latin America, that extreme poor Mexicans don't migrate although the moderately poor do, that remittances have a small, non-significant impact on the most widely used inequality index of all households and a very large one on the inequality index of remittance-receiving households, and finally that, to Mexican households, the opportunity cost of international migration is higher than remittance income. In summary, there is a relationship between poverty and migration (and vice versa), but this relationship is far from linear, and in some respects may be a perverse one for Mexico and for Mexican households.

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