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• W3012960443 abstract "Multiple mechanisms have been detected to account for the acquired resistance to endocrine therapies in breast cancer. In this study we retrospectively studied the mechanism of primary endocrine resistance in estrogen receptor positive (ER+) breast cancer patients by next-generation sequencing (NGS). Tumor specimens and matched blood samples were obtained from 24 ER+ breast cancer patients. Fifteen of them displayed endocrine resistance, including recurrence and/or metastases within 24 months from the beginning of endocrine therapy, and 9 patients remained sensitive to endocrine therapy for more than 5 years. Genomic DNA of tumor tissue was extracted from formalin-fixed paraffin-embedded (FFPE) tumor tissue blocks. Genomic DNA of normal tissue was extracted from peripheral blood mononuclear cells (PBMC). Sequencing libraries for each sample were prepared, followed by target capturing for 372 genes that are frequently rearranged in cancers. Massive parallel sequencing was then performed using Illumina NextSeq 500, and samples with a mean sequencing depth of 500× were analyzed. The analysis revealed that 8 (55%) of 15 patients showed phosphatidylinositol 3-kinase CA (PIK3CA) mutations, including 3 pathogenic variants in kinase domain, 3 pathogenic variants in helical domain, and 2 variants of unknown significance, in the endocrine-resistant group, while 3 (33%) of 9 patients displayed PIK3CA mutations, including 2 pathogenic variants in kinase domain and 1 pathogenic variant in helical domain, in the endocrine-sensitive group. In the endocrine-sensitive group, copy number gain of C11orf30 (EMSY) gene, copy number loss of CDH1 (E-cadherin) gene, and a missense mutation of splicing factor 3b (SF3B1) gene were also detected, which would probably decrease the expression of ESR1 and contribute to endocrine sensitivity. Collectively, the PIK3CA mutation rate in the resistance group is relatively higher than that in the sensitive group and thus PIK3CA mutations may contribute the primary endocrine resistance of breast cancer." @default.
• W3012960443 created "2020-04-03" @default.
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• W3012960443 date "2018-01-01" @default.
• W3012960443 modified "2023-10-18" @default.
• W3012960443 title "Impact of next-generation sequencing (NGS) for primary endocrine resistance in breast cancer patients." @default.
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