scholarly journals Analysis of Pathogenic Variants in BRCA1 and BRCA2 Genes using Next-Generation Sequencing in Women with Triple Negative Breast Cancer from South India

2021 ◽  
Author(s):  
Taruna Rajagopal ◽  
Arun Seshachalam ◽  
Arunachalam Jothi ◽  
Krishna Kumar Rathnam ◽  
Srikanth Talluri ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Brca Mutation ◽  
Mutation Screening ◽  
Preventive Therapy ◽  
Brca1 And Brca2 ◽  
Indian Women ◽  
Pathogenic Variants ◽  
South Indian

Abstract The frequency of triple-negative breast cancer (TNBC) incidence varies among different populations, suggesting the involvement of genetic component towards TNBC development. Previous studies have reported that BRCA1/2 germline mutations confer a lifetime risk of developing TNBC. However, there is hardly any information regarding the common pathogenic variants (PVs) in BRCA1/2 genes that contribute to TNBC in the Indian population. Hence, we screened for PVs in BRCA1/2 and their association with clinico-pathological features in TNBC patients. Among the 59 TNBC genomic DNA samples sequenced, 8 BRCA mutations were detected in 59 TNBC patients (13.6%). Almost 50% pre-menopausal TNBC patients had a BRCA mutation. Of the 8 BRCA mutations, we observed BRCA1 mutations in 6 TNBC patients, and BRCA2 mutations in 2 TNBC patients. Among the 6 BRCA1 mutations, three were c.68_69delAG (185delAG) mutation. Remarkably, all the TNBC patients with BRCA mutations exhibited higher-grade tumors (grade 2 or 3). However, among the BRCA mutation carriers, only one patient with a BRCA2 mutation (p.Glu1879Lys) developed metastasis in the observed cohort. Our data advocates that South Indian women with higher grade TNBC tumors and without hereditary breast and ovarian cancer should be considered for BRCA mutation screening, thereby enabling enhanced decision-making and preventive therapy.

scholarly journals Associations of pathogenic mutations responsible for breast cancer risk with histology and immunohistochemistry in Romanian population

2018 ◽  
Vol 26 (2) ◽  
pp. 165-175 ◽  
Author(s):  
Iulian Gabriel Goidescu ◽  
Dan Tudor Eniu ◽  
Gabriela Valentina Caracostea ◽  
Gheorghe Cruciat ◽  
Florin Stamatian
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Ductal Carcinoma ◽  
Breast Cancer Patients ◽  
Brca1 And Brca2 ◽  
Pathogenic Variants ◽  
Romanian Population ◽  
First Time ◽  
Histology And Immunohistochemistry

Abstract Introduction: Breast cancer is the most common cancer in women worldwide, and Romania makes no exception from this trend. Genetic screening for Hereditary Breast and Ovarian Cancer began to be used on a larger scale after the introduction of Next Generation Sequencing. The aim of this study was to assess the association of deleterious mutations responsible for breast cancer with histopathological and immunohistochemical prognostic factors and to identify some genetic variants in the BRCA1 and BRCA2 genes. Method: 80 patients with breast cancer and negative genetic test or pathogenic variants on BRCA1/2, TP53, PALB2, CHEK2, ATM genes were included. All the cases had a prior histological diagnosis and complete immunohistochemical features. The genetic testing was conducted through a multigene panel. Results: 65% of patients had a deleterious mutation on BRCA genes. In 97.5% of cases the histology was invasive ductal carcinoma. Significant differences were identified between BRCA1 group and negative mutation group regarding estrogen receptor (ER) (p=0.0051), progesterone receptor (PR) (p=0.0004) and Ki67 (p=0.001). Seven breast cancer patients had BRCA1 c.3607C>T variant, which was statistically significantly associated with triple- negative breast cancer (p <0.0001). Of the 7 cases diagnosed with BRCA 2 mutations we identified the c.8755-1G>A variant in 3 cases and the c.9371A>T variant in 3 cases. Discussion and conclusion: Our study confirmed the association of BRCA1 mutations with negative ER, PR or triple negative breast cancer (TNBC). Description of BRCA1 c.3607C>T mutation for the first time in Romanian population and its association with TNBC will need further investigation.

scholarly journals Assessment of genetic referrals and outcomes for women with triple negative breast cancer in regional cancer centres in Australia

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Lucie G. Hallenstein ◽  
Carol Sorensen ◽  
Lorraine Hodgson ◽  
Shelly Wen ◽  
Justin Westhuyzen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Genetic Testing ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Cancer Genetics ◽  
Eligibility Criteria ◽  
Pathogenic Variants ◽  
Genetics Services ◽  
Age Of Diagnosis ◽  
Over Time

Abstract Background Guidelines for referral to cancer genetics service for women diagnosed with triple negative breast cancer have changed over time. This study was conducted to assess the changing referral patterns and outcomes for women diagnosed with triple negative breast cancer across three regional cancer centres during the years 2014–2018. Methods Following ethical approval, a retrospective electronic medical record review was performed to identify those women diagnosed with triple negative breast cancer, and whether they were referred to a genetics service and if so, the outcome of that genetics assessment and/or genetic testing. Results There were 2441 women with newly diagnosed breast cancer seen at our cancer services during the years 2014–2018, of whom 237 women were diagnosed with triple negative breast cancer. Based on age of diagnosis criteria alone, 13% (31/237) of our cohort fulfilled criteria for genetic testing, with 81% (25/31) being referred to a cancer genetics service. Of this group 68% (21/31) were referred to genetics services within our regions and went on to have genetic testing with 10 pathogenic variants identified; 5x BRCA1, 4x BRCA2 and × 1 ATM:c.7271 T > G. Conclusions Referral pathways for women diagnosed with TNBC to cancer genetics services are performing well across our cancer centres. We identified a group of women who did not meet eligibility criteria for referral at their time of diagnosis, but would now be eligible, as guidelines have changed. The use of cross-discipline retrospective data reviews is a useful tool to identify patients who could benefit from being re-contacted over time for an updated cancer genetics assessment.

scholarly journals Influence of Germline BRCA Genotype on the Survival of Patients with Triple-Negative Breast Cancer

2021 ◽  
Vol 1 (3) ◽  
pp. 140-147
Author(s):  
Cynthia Villarreal-Garza ◽  
Ana S. Ferrigno ◽  
Alejandro Aranda-Gutierrez ◽  
Paul H. Frankel ◽  
Nora H. Ruel ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Point Mutations ◽  
Treatment Resistance ◽  
Cancer Center ◽  
Breast Cancers ◽  
Entire Cohort ◽  
Pathogenic Variants ◽  
Mutational Status

The presence of BRCA pathogenic variants (PV) in triple-negative breast cancer (TNBC) is associated with a distinctive genomic profile that makes the tumor particularly susceptible to DNA-damaging treatments. However, patients with BRCA PVs can develop treatment resistance through the appearance of reversion mutations and restored BRCA expression. As copy-number variants (CNV) could be less susceptible to reversion mutations than point mutations, we hypothesize that carriers of BRCA CNVs may have improved survival after treatment compared with carriers of other BRCA PVs or BRCA wild-type. Women diagnosed with stage I–III TNBC at ≤50 years at a cancer center in Mexico City were screened for BRCA PVs using a recurrent PV assay (HISPANEL; 77% sensitivity). Recurrence-free survival (RFS) and overall survival (OS) were compared according to the mutational status. Among 180 women, 17 (9%) were carriers of BRCA1 ex9–12del CNVs and 26 (14%) of other BRCA PVs. RFS at ten years for the whole cohort was 79.2% [95% confidence interval (CI), 72.3–84.6], with no significant differences according to mutational status. 10-year OS for the entire cohort was 85.3% (95% CI, 78.7–90.0), with BRCA CNV carriers demonstrating numerically superior OS rates other PV carriers and noncarriers (100% vs. 78.6% and 84.7%; log-rank P = 0.037 and P = 0.051, respectively). This study suggests that BRCA1 ex9–12del CNV carriers with TNBC may have a better OS, and supports the hypothesis that the genotype of BRCA PVs may influence survival by limiting treatment resistance mediated by reversion mutations among CNV carriers. Significance: Large CNV BRCA carriers in a cohort of young Mexican patients with TNBC had superior OS rates than carriers of other BRCA pathogenic variants (i.e., small indels or point mutations). We hypothesize that this is due to the resistance of CNVs to reversion mutations mediating resistance to therapy. If validated, these findings have important prognostic and clinical treatment implications for BRCA-associated breast cancers.

scholarly journals Triple-negative breast cancer and BRCA mutation: looking at the future

2016 ◽  
Vol 27 ◽  
pp. iv66
Author(s):  
Z. Ballatore ◽  
M. Pistelli ◽  
R. Bracci ◽  
F. Bianchi ◽  
E. Maccaroni ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Brca Mutation ◽  
The Future

scholarly journals PARP Inhibitor Olaparib Use in a BRCA1-Positive Patient With Metastatic Triple-Negative Breast Cancer, Without the Initial Use of Platinum-Based Chemotherapy, Showing Significant Rapid Near Resolution of Large Liver Metastasis While Patient Experienced Gout-Like Symptoms

2019 ◽  
Vol 7 ◽  
pp. 232470961986498 ◽  
Author(s):  
Trevanne Matthews Hew ◽  
Lara Zuberi
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Brca Mutation ◽  
Parp Inhibitor ◽  
Parp Inhibitors ◽  
Management Options ◽  
Federal Drug Administration ◽  
Platinum Based Chemotherapy ◽  
Metastatic Setting

Triple-negative breast cancer (TNBC) accounts for 20% of breast cancers diagnosed worldwide. This subtype of breast cancer tends to behave more aggressively, and unlike other breast cancer subtypes, there are no standard targeted treatments for most patients. However, up to 20% of patients with TNBC harbor a breast cancer gene (BRCA) mutation, particularly in BRCA1. For patients who carry this gene mutation, this opens the door for new management options by the use of newer agents such as polyadenosine diphosphate-ribose polymerase (PARP) inhibitors in the metastatic setting. Given that this is uncommon and that PARP inhibitors have only recently received Federal Drug Administration approval, the experience with these drugs is relatively new. In this article, we present a case of a patient treated in this setting with olaparib who developed an unanticipated side effect as a result of the high efficacy of the drug.

scholarly journals Phase I Study of Veliparib (ABT-888) Combined with Cisplatin and Vinorelbine in Advanced Triple-Negative Breast Cancer and/or BRCA Mutation–Associated Breast Cancer

2016 ◽  
Vol 22 (12) ◽  
pp. 2855-2864 ◽  
Author(s):  
Eve T. Rodler ◽  
Brenda F. Kurland ◽  
Melissa Griffin ◽  
Julie R. Gralow ◽  
Peggy Porter ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Phase I ◽  
Triple Negative Breast Cancer ◽  
Phase I Study ◽  
Triple Negative ◽  
Brca Mutation

Breast cancer associated pathogenic variants among women 61 years and older with triple negative breast cancer

2020 ◽  
Author(s):  
Yanin Chávarri-Guerra ◽  
Catherine A. Marcum ◽  
Carolyn B. Hendricks ◽  
Deborah Wilbur ◽  
Terrence Cescon ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Pathogenic Variants

scholarly journals BRCA1/2 Mutations and Bevacizumab in the Neoadjuvant Treatment of Breast Cancer: Response and Prognosis Results in Patients With Triple-Negative Breast Cancer From the GeparQuinto Study

2018 ◽  
Vol 36 (22) ◽  
pp. 2281-2287 ◽  
Author(s):  
Peter A. Fasching ◽  
Sibylle Loibl ◽  
Chunling Hu ◽  
Steven N. Hart ◽  
Hermela Shimelis ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Strong Predictor ◽  
Pathologic Complete Response ◽  
Neoadjuvant Treatment ◽  
Disease Free Survival ◽  
Hazard Ratio ◽  
Brca1 And Brca2 ◽  
Mutation Carriers

Purpose BRCA1/2 mutations are frequent in patients with triple-negative breast cancer (TNBC). These patients are often treated with primary systemic chemotherapy. The aim of this study was to analyze the effects of BRCA1/2 mutations on pathologic complete response (pCR) and disease-free survival (DFS) in a cohort of patients with TNBC treated with anthracycline and taxane–containing chemotherapy, with or without bevacizumab. Patients and Methods Germline DNA was sequenced to identify mutations in BRCA1 and BRCA2 in 493 patients with TNBC from the GeparQuinto study. The pCR rates were compared in patients with and without mutation, as well as in patients treated with and without bevacizumab. In addition, the influence of BRCA1/2 mutation status and pCR status on DFS was evaluated relative to treatment. Results BRCA1/2 mutations were detected in 18.3% of patients with TNBC. Overall, patients with mutations had a pCR rate of 50%, compared with 31.5% in patients without a mutation (odds ratio [OR], 2.17; 95% CI, 1.37 to 3.46; P = .001). The pCR rate among patients treated with bevacizumab was 61.5% for BRCA1/2 mutation carriers and 35.6% for those without mutations (OR, 2.90; 95% CI, 1.43 to 5.89; P = .004). pCR was a strong predictor of DFS for patients without BRCA1/2 mutations (hazard ratio, 0.18; 95% CI, 0.11 to 0.31) but not for patients with BRCA1/2 mutations (hazard ratio, 0.74; 95% CI, 0.32 to 1.69). Conclusion The addition of bevacizumab may increase the pCR after standard neoadjuvant chemotherapy for patients with TNBC with BRCA1/2 mutations. In patients treated with anthracycline and taxane–based chemotherapy (with or without bevacizumab), pCR was a weaker predictor of DFS for BRCA1/2 mutation carriers than for patients without mutations.

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