BACKGROUND: The epidermal growth factor receptor (EGFR) is a potential therapeutic target for breast cancer; however, its use does not lead to a marked clinical response. Studies of non-small cell lung cancer and colorectal cancer showed that mutations of genes in the PIK3CA/AKT and RAS/RAF/MEK pathways, two major signalling cascades downstream of EGFR, might predict resistance to EGFR-targeted agents. Therefore, we examined the frequencies of mutations in these key EGFR pathway genes in Chinese breast cancer patients. METHODS: We used a high-throughput mass-spectrometric based cancer gene mutation profiling platform to detect 22 mutations of the PIK3CA, AKT1, BRAF, EGFR, HRAS, and KRAS genes in 120 Chinese women with breast cancer. RESULTS: Thirteen mutations were detected in 12 (10%) of the samples, all of which were invasive ductal carcinomas (two stage I, six stage II, three stage III, and one stage IV). These included one mutation (0.83%) in the EGFR gene (rs121913445-rs121913432), three (2.5%) in the KRAS gene (rs121913530, rs112445441), and nine (7.5%) in the PIK3CA gene (rs121913273, rs104886003, and rs121913279). No mutations were found in the AKT1, BRAF, and HRAS genes. Six (27.3%) of the 22 genotyping assays caused mutations in at least one sample and three (50%) of the six assays queried were found to be mutated more than once. CONCLUSIONS: Mutations in the EGFR pathway occurred in a small fraction of Chinese breast cancers. However, therapeutics targeting these potential predictive markers should be investigated in depth, especially in Oriental populations.
BACKGROUND: The epidermal growth factor receptor (EGFR) is a potential therapeutic target for breast cancer; however, its use does not lead to a marked clinical response. Studies of non-small cell lung cancer and colorectal cancer showed that mutations of genes in the PIK3CA/AKT and RAS/RAF/MEK pathways, two major signalling cascades downstream of EGFR, might predict resistance to EGFR-targeted agents. Therefore, we examined the frequencies of mutations in these key EGFR pathway genes in Chinese breast cancerpatients. METHODS: We used a high-throughput mass-spectrometric based cancer gene mutation profiling platform to detect 22 mutations of the PIK3CA, AKT1, BRAF, EGFR, HRAS, and KRAS genes in 120 Chinese women with breast cancer. RESULTS: Thirteen mutations were detected in 12 (10%) of the samples, all of which were invasive ductal carcinomas (two stage I, six stage II, three stage III, and one stage IV). These included one mutation (0.83%) in the EGFR gene (rs121913445-rs121913432), three (2.5%) in the KRAS gene (rs121913530, rs112445441), and nine (7.5%) in the PIK3CA gene (rs121913273, rs104886003, and rs121913279). No mutations were found in the AKT1, BRAF, and HRAS genes. Six (27.3%) of the 22 genotyping assays caused mutations in at least one sample and three (50%) of the six assays queried were found to be mutated more than once. CONCLUSIONS: Mutations in the EGFR pathway occurred in a small fraction of Chinese breast cancers. However, therapeutics targeting these potential predictive markers should be investigated in depth, especially in Oriental populations.
Authors: Huiying Liang; Xuexi Yang; Lujia Chen; Hong Li; Anna Zhu; Minying Sun; Haitao Wang; Ming Li Journal: Biomed Res Int Date: 2015-09-03 Impact factor: 3.411
Authors: Silvia von der Heyde; Steve Wagner; Alexander Czerny; Manuel Nietert; Fabian Ludewig; Gabriela Salinas-Riester; Dorit Arlt; Tim Beißbarth Journal: PLoS One Date: 2015-02-24 Impact factor: 3.240
Authors: Niek Hugen; Michiel Simons; Altuna Halilović; Rachel S van der Post; Anna J Bogers; Monica Aj Marijnissen-van Zanten; Johannes Hw de Wilt; Iris D Nagtegaal Journal: J Pathol Clin Res Date: 2014-11-05
Authors: Haibo Wu; Wei Wang; Jun Du; Hong Li; Huogang Wang; Liangliang Huang; Hang Xiang; Jing Xie; Xiaoli Liu; Heng Li; Wenchu Lin Journal: Cancer Manag Res Date: 2019-02-14 Impact factor: 3.989