scholarly journals Triple-negative breast cancer and PTEN (phosphatase and tensin homologue)loss are predictors of BRCA1 germline mutations in women with early-onset and familial breast cancer, but not in women with isolated late-onset breast cancer

2012 ◽  
Vol 14 (6) ◽  
Author(s):  
Sze-Yee Phuah ◽  
Lai-Meng Looi ◽  
Norhashimah Hassan ◽  
Anthony Rhodes ◽  
Sarah Dean ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Early Onset ◽  
Familial Breast Cancer ◽  
Triple Negative ◽  
Late Onset ◽  
Germline Mutations ◽  
Phosphatase And Tensin Homologue

BRCA1 deficiency is a recurrent event in early-onset triple-negative breast cancer: a comprehensive analysis of germline mutations and somatic promoter methylation

2017 ◽  
Vol 167 (3) ◽  
pp. 803-814 ◽  
Author(s):  
Rafael Canfield Brianese ◽  
Kivvi Duarte de Mello Nakamura ◽  
Fernanda Gabriella dos Santos Ramos Almeida ◽  
Rodrigo Fernandes Ramalho ◽  
Bruna Durães de Figueiredo Barros ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Promoter Methylation ◽  
Early Onset ◽  
Triple Negative ◽  
Germline Mutations ◽  
Comprehensive Analysis ◽  
Recurrent Event

scholarly journals BRCA Detection Rate in an Italian Cohort of Luminal Early-Onset and Triple-Negative Breast Cancer Patients without Family History: When Biology Overcomes Genealogy

Cancers ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 1252 ◽  
Author(s):  
Angela Toss ◽  
Eleonora Molinaro ◽  
Marta Venturelli ◽  
Federica Domati ◽  
Luigi Marcheselli ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Genetic Testing ◽  
Family History ◽  
Triple Negative Breast Cancer ◽  
Early Onset ◽  
Detection Rate ◽  
Triple Negative ◽  
Brca2 Mutation ◽  
Brca Testing ◽  
Brca Genetic Testing

NCCN Guidelines recommend BRCA genetic testing in individuals with a probability >5% of being a carrier. Nonetheless, the cost-effectiveness of testing individuals with no tumor family history is still debated, especially when BRCA testing is offered by the national health service. Our analysis evaluated the rate of BRCA pathogenic or likely-pathogenic variants in 159 triple-negative breast cancer (TNBC) patients diagnosed ≤60 years, and 109 luminal-like breast cancer (BC) patients diagnosed ≤35 without breast and/or ovarian family histories. In TNBC patients, BRCA mutation prevalence was 22.6% (21.4% BRCA1). Mutation prevalence was 64.2% ≤30 years, 31.8% in patients aged 31–40, 16.1% for those aged 41–50 and 7.9% in 51–60 s. A total of 40% of patients with estrogen receptors (ER) 1–9% were BRCA1 carriers. BRCA detection rate in early-onset BCs was 6.4% (4.6% BRCA2). Mutation prevalence was 0% between 0–25 years, 9% between 26–30 years and 6% between 31–35 years. In conclusion, BRCA testing is recommended in TNBC patients diagnosed ≤60 years, regardless of family cancer history or histotype, and by using immunohistochemical staining <10% for both ER and/PR. In luminal-like early-onset BC, a lower BRCA detection rate was observed, suggesting a role for other predisposing genes along with BRCA genetic testing.

scholarly journals Integrating Germline and Somatic Mutation Information for the Discovery of Biomarkers in Triple-Negative Breast Cancer

2019 ◽  
Vol 16 (6) ◽  
pp. 1055 ◽  
Author(s):  
Jiande Wu ◽  
Tarun Mamidi ◽  
Lu Zhang ◽  
Chindo Hicks
Keyword(s):  
Breast Cancer ◽  
Somatic Mutation ◽  
Triple Negative Breast Cancer ◽  
Somatic Mutations ◽  
Triple Negative ◽  
Germline Mutations ◽  
Biological Pathways ◽  
Molecular Networks ◽  
Increased Risk ◽  
Mutation Information

Recent advances in high-throughput genotyping and the recent surge of next generation sequencing of the cancer genomes have enabled discovery of germline mutations associated with an increased risk of developing breast cancer and acquired somatic mutations driving the disease. Emerging evidence indicates that germline mutations may interact with somatic mutations to drive carcinogenesis. However, the possible oncogenic interactions and cooperation between germline and somatic alterations in triple-negative breast cancer (TNBC) have not been characterized. The objective of this study was to investigate the possible oncogenic interactions and cooperation between genes containing germline and somatic mutations in TNBC. Our working hypothesis was that genes containing germline mutations associated with an increased risk developing breast cancer also harbor somatic mutations acquired during tumorigenesis, and that these genes are functionally related. We further hypothesized that TNBC originates from a complex interplay among and between genes containing germline and somatic mutations, and that these complex array of interacting genetic factors affect entire molecular networks and biological pathways which in turn drive the disease. We tested this hypothesis by integrating germline mutation information from genome-wide association studies (GWAS) with somatic mutation information on TNBC from The Cancer Genome Atlas (TCGA) using gene expression data from 110 patients with TNBC and 113 controls. We discovered a signature of 237 functionally related genes containing both germline and somatic mutations. We discovered molecular networks and biological pathways enriched for germline and somatic mutations. The top pathways included the hereditary breast cancer and role of BRCA1 in DNA damage response signaling pathways. In conclusion, this is the first large-scale and comprehensive analysis delineating possible oncogenic interactions and cooperation among and between genes containing germline and somatic mutations in TNBC. Genetic and somatic mutations, along with the genes discovered in this study, will require experimental functional validation in different ethnic populations. Functionally validated genetic and somatic variants will have important implications for the development of novel precision prevention strategies and discovery of prognostic markers in TNBC.

scholarly journals Insights Into the Impacts of BRCA Mutations on Clinicopathology and Management of Early-Onset Triple-Negative Breast Cancer

2021 ◽  
Vol 10 ◽  
Author(s):  
Fugui Ye ◽  
Min He ◽  
Liang Huang ◽  
Guantian Lang ◽  
Xin Hu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Early Onset ◽  
Triple Negative ◽  
Brca Mutation ◽  
Oncologic Outcomes ◽  
Treatment Modalities ◽  
Brca Mutations ◽  
Clinicopathologic Characteristics ◽  
Cancer Specific Survival

BackgroundLittle is known regarding the clinicopathologic characteristics, oncologic outcomes, and treatment strategies that could be ascribed to BRCA mutation in early-onset triple-negative breast cancer (eTNBC).MethodseTNBC patients who underwent BRCA genetic testing were derived from our clinical database between 2012 and 2018. Differences in clinical features and pathologic characteristics were examined in groups divided by BRCA mutation status, and the contribution of germline mutations in conjunction with treatment modalities to survival outcomes was determined.ResultsOf the 355 qualifying eTNBC patients, 67 (18.87%) were BRCA mutated and 288 (81.13%) were BRCA wild. Overall, median age at diagnosis was 34 years (range, 24–40 years) in the BRCA mutated subgroup and 35 years (range, 21–40 years) in BRCA wild. The majority of clinicopathologic parameters were parallel; however, tumor size (P = 0.07) and nuclear grade (P =0.08) tend to be more aggressive in the BRCA mutated subgroup. Compared with BRCA wild patients, BRCA mutated patients had a higher likelihood of receiving anthracyclines and taxane-based combination chemotherapy (P = 0.04) and tend to be lower tumor burden (P =0.01). After approximately 5-year median follow-up, the overall survival (OS) (P = 0.021) and breast cancer-specific survival (BCSS) (P = 0.004) in BRCA mutated patients were superior to those in their BRCA wild counterparts. Intriguingly, the clinical outcomes were comparable in patients with breast conserving surgery (BCS) regardless of BRCA mutations and in patients with BRCA mutations in spite of surgical schedules.ConclusionsThese results suggest that eTNBC patients with BRCA mutations are prone to better OS and BCSS, which might be largely attributed to more benefit from anthracyclines and taxane-based chemotherapy. The BCS procedure could be a safe alternative surgical option for eTNBC patients with BRCA mutations. Future studies with substantial numbers of participants are urgently needed to validate whether BRCA mutation eTNBC patients are more sensitive to chemotherapy.

scholarly journals Early‐onset triple‐negative breast cancer in multiracial/ethnic populations: Distinct trends of prevalence of truncation mutations

2019 ◽  
Vol 8 (4) ◽  
pp. 1845-1853 ◽  
Author(s):  
Qian Liu ◽  
Song Yao ◽  
Hua Zhao ◽  
Qiang Hu ◽  
Marilyn L. Kwan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Early Onset ◽  
Triple Negative ◽  
Ethnic Populations

scholarly journals Screening of BRCA1 and BRCA2 germline mutations in unselected triple‐negative breast cancer patients: A series from north of Morocco

2020 ◽  
Vol 9 (1) ◽  
pp. 43-48
Author(s):  
Mohammed Mansouri ◽  
Touria Derkaoui ◽  
Joaira Bakkach ◽  
Ali Loudiyi ◽  
Naima Ghailani Nourouti ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Germline Mutations ◽  
Breast Cancer Patients ◽  
Brca1 And Brca2

Molecular Features and Functional Implications of Germline Variants in Triple-Negative Breast Cancer

2020 ◽  
Author(s):  
Ding Ma ◽  
Si-Yu Chen ◽  
Jin-Xiao Ren ◽  
Yu-Chen Pei ◽  
Cong-Wei Jiang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Early Onset ◽  
Triple Negative ◽  
Parp Inhibitors ◽  
Chinese Patients ◽  
Molecular Characteristics ◽  
Germline Variants ◽  
Molecular Features ◽  
Germline Variant

Abstract Background The germline variant spectrum of triple-negative breast cancer (TNBC) is different from that of other subtypes and has demonstrated ethnic differences. However, the germline variants of TNBC among Chinese patients and its clinical significance remain unclear. Methods Using our multi-omics TNBC cohort (n = 325), we determined the spectrum of germline variants in TNBC and aimed to illustrate their biological and clinical implications. Results Overall, 16.0% (52 of 325) of TNBC patients harbored at least 1 pathogenic or likely pathogenic germline variant. These germline variants were associated with early onset of TNBC, the occurrence of contralateral breast cancer, the basal-like immune-suppressed mRNA subtype, and the homologous recombination deficiency (HRD) mutation subtype. Somatic allele-specific imbalance was observed in 54.1% of these germline variants, which was correlated with early onset of breast cancer and elevated HRD. The genes BRCA1 (7.4%), RAD51D (2.8%), and BRCA2 (2.2%) were those most frequently mutated. The RAD51D germline variants, especially K91fs, were enriched in Chinese patients with TNBC compared with Caucasian and African American patients. The Chinese-specific RAD51D germline variants were functionally associated with the instability of the RAD51D protein, HRD, and sensitivity to PARP inhibitors. Conclusions Chinese TNBC patients have a distinct spectrum of germline variants, with a remarkable impact on the clinical and molecular characteristics of the tumor. Integrative germline-somatic analysis may help identify TNBC patients who are most likely to be affected by their germline variants and in performing clinical interventions more precisely. The RAD51D variants enriched in our cohort may serve as therapeutic targets and guide precision treatment of TNBC.

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