An Exploration of Mutation Status of Cancer Genes in Breast Cancers

Wang, Qianqian

doi:10.4172/2469-9853.1000103

Cited by 3 publications

(3 citation statements)

References 37 publications

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“…Furthermore, one patient in the present study with no germline BRCA1 pathogenic variants had a primary tumor with a somatic BRCA1 gene mutation. De novo somatic BRCA1/2 mutations in breast cancer are considered to be rare: the prevalence of somatic BRCA1 gene mutations in primary tumors is only 1.55%, and that of somatic BRCA2 gene mutations is 1.68% 42 . Although the clinical success of PARP inhibitors for women with germline BRCA1/2 pathogenic variants is clear, the utility of using PARP inhibition to treat breast cancers with somatic BRCA1/2 mutations is not known.…”

Section: Discussionmentioning

confidence: 99%

Impact of clinical targeted sequencing on endocrine responsiveness in estrogen receptor-positive, HER2-negative metastatic breast cancer

Hagio

Amano

Hayashi

et al. 2021

Sci Rep

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Clinical targeted sequencing allows for the selection of patients expected to have a better treatment response, and reveals mechanisms of resistance to molecular targeted therapies based on actionable gene mutations. We underwent comprehensive genomic testing with either our original in-house CLHURC system or with OncoPrime. Samples from 24 patients with estrogen receptor-positive, human epidermal growth factor receptor 2-negative metastatic breast cancer underwent targeted sequencing between 2016 and 2018. Germline and somatic gene alterations and patients’ prognosis were retrospectively analyzed according to the response to endocrine therapy. All of the patients had one or more germline and/or somatic gene alterations. Four patients with primary or secondary endocrine-resistant breast cancer harbored germline pathogenic variants of BRCA1, BRCA2, or PTEN. Among somatic gene alterations, TP53, PIK3CA, AKT1, ESR1, and MYC were the most frequently mutated genes. TP53 gene mutation was more frequently observed in patients with primary endocrine resistance compared to those with secondary endocrine resistance or endocrine-responsive breast cancer. Recurrent breast cancer patients carrying TP53-mutant tumors had significantly worse overall survival compared to those with TP53-wild type tumors. Our 160-gene cancer panel will be useful to identify clinically actionable gene alterations in breast cancer in clinical practice.

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Section: Discussionmentioning

confidence: 99%

Impact of clinical targeted sequencing on endocrine responsiveness in estrogen receptor-positive, HER2-negative metastatic breast cancer

Hagio

Amano

Hayashi

et al. 2021

Sci Rep

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“…Our study, in line with other studies, indicated that the longitudinal follow-up of ctDNA mutations outperformed imaging in indicating the response to therapy [ 29 ]. Indeed, we also found that serial plasma ctDNA determinations can sensitively predict disease relapse several months earlier than the time of clinical progression and inferior outcome [ 13 , 28 , 31 , 32 ]. Several studies pointed to the use of ctDNA technology in post-surgery cases for the detection of minimal residual disease or progression or even for screening high breast cancer risks in healthy individuals [ 30 ].…”

Section: Discussionmentioning

confidence: 99%

“…We selected somatic variants from tier I and II that contain breast cancer-specific drug-matched alterations and supplemented them with TP53, one of the most frequent alterations in breast cancer, to increase the traceability of the tumor at the plasma level. The final list of targets ( Table 1 ) was specified based on recent scientific and clinical literature highlighting the frequent somatic alterations in human breast cancer samples [ 13 ].…”

Section: Methodsmentioning

confidence: 99%

BC-Monitor: Towards a Routinely Accessible Circulating Tumor DNA-Based Tool for Real-Time Monitoring Breast Cancer Progression and Treatment Effectiveness

Priskin¹,

Pólya²,

Pintér³

et al. 2021

Cancers

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Circulating tumor DNA (ctDNA) is increasingly employed in the screening, follow-up, and monitoring of the continuously evolving tumor; however, most ctDNA assays validated for clinical use cannot maintain the right balance between sensitivity, coverage, sample requirements, time, and cost. Here, we report our BC-monitor, a simple, well-balanced ctDNA diagnostic approach using a gene panel significant in breast cancer and an optimized multiplex PCR-based NGS protocol capable of identifying allele variant frequencies below 1% in cell-free plasma DNA. We monitored a cohort of 45 breast cancer patients prospectively enrolled into our study receiving neoadjuvant chemotherapy or endocrine therapy or palliative therapy for metastatic diseases. Their tumor mutation status was examined in the archived tumor samples and plasma samples collected before and continuously during therapy. Traceable mutations of the used 38-plex NGS assay were found in approximately two-thirds of the patients. Importantly, we detected new pathogenic variants in follow-up plasma samples that were not detected in the primary tumor and baseline plasma samples. We proved that the BC-monitor can pre-indicate disease progression four–six months earlier than conventional methods. Our study highlights the need for well-designed ctDNA monitoring during treatment and follow-up, integrated into a real-time treatment assessment, which could provide information on the active tumor DNA released into the blood.

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Identification of Somatically AcquiredBRCA1/2Mutations by cfDNA Analysis in Patients with Metastatic Breast Cancer

Vidula

Dubash

Lawrence

et al. 2020

Clinical Cancer Research

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Purpose: Plasma genotyping may identify mutations in potentially “actionable” cancer genes, such as BRCA1/2, but their clinical significance is not well-defined. We evaluated the characteristics of somatically acquired BRCA1/2 mutations in patients with metastatic breast cancer (MBC). Experimental Design: Patients with MBC undergoing routine cell-free DNA (cfDNA) next-generation sequencing (73-gene panel) before starting a new therapy were included. Somatic BRCA1/2 mutations were classified as known germline pathogenic mutations or novel variants, and linked to clinicopathologic characteristics. The effect of the PARP inhibitor, olaparib, was assessed in vitro, using cultured circulating tumor cells (CTCs) from a patient with a somatically acquired BRCA1 mutation and a second patient with an acquired BRCA2 mutation. Results: Among 215 patients with MBC, 29 (13.5%) had somatic cfDNA BRCA1/2 mutations [nine (4%) known germline pathogenic and rest (9%) novel variants]. Known germline pathogenic BRCA1/2 mutations were common in younger patients (P = 0.008), those with triple-negative disease (P = 0.022), and they were more likely to be protein-truncating alterations and be associated with TP53 mutations. Functional analysis of a CTC culture harboring a somatic BRCA1 mutation demonstrated high sensitivity to PARP inhibition, while another CTC culture harboring a somatic BRCA2 mutation showed no differential sensitivity. Across the entire cohort, APOBEC mutational signatures (COSMIC Signatures 2 and 13) and the “BRCA” mutational signature (COSMIC Signature 3) were present in BRCA1/2-mutant and wild-type cases, demonstrating the high mutational burden associated with advanced MBC. Conclusions: Somatic BRCA1/2 mutations are readily detectable in MBC by cfDNA analysis, and may be present as both known germline pathogenic and novel variants.

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An Exploration of Mutation Status of Cancer Genes in Breast Cancers

Cited by 3 publications

References 37 publications

Impact of clinical targeted sequencing on endocrine responsiveness in estrogen receptor-positive, HER2-negative metastatic breast cancer

Impact of clinical targeted sequencing on endocrine responsiveness in estrogen receptor-positive, HER2-negative metastatic breast cancer

BC-Monitor: Towards a Routinely Accessible Circulating Tumor DNA-Based Tool for Real-Time Monitoring Breast Cancer Progression and Treatment Effectiveness

Identification of Somatically AcquiredBRCA1/2Mutations by cfDNA Analysis in Patients with Metastatic Breast Cancer

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