There were some medical information demonstrating that lapatinib induced objective responses in patients who had failed trastuzumab. First, only two exons accounting for about 850-488 of all mutations were determined within our study. Next, mutation correlates with an old-age and this phenomenon was confirmed by our study. But, the median age of our Cyclopamine 4449-51-8 patients was 49. . 0 years, about 10 years younger than Caucasian counterparts. Third, the mutation was reported to occur more frequently in HER2 bad patients, but, all patients in our study were HER2 positive. Regarding variations in hot-spots, two common mutation items, H1047R and E542K were also within our patients with no mutation of E545K observed. As to mutations in non hot spots, T1052A mutations, L540F and two new factors were first reported depending on our knowledge. An evaluation of our data showed the proportion of hot spots to low hot spots was 2. 5 to 1, which is consistent with other studies. Because there have been only a few people with the new mutation, further confirmation was needed by our result by other studies. Consequently, it remains a question whether the new Cholangiocarcinoma mutation in non hot spots in a activation of PI3K pathway. As in other studies, these patients were thought to have a mutated gene in the research. PTEN is a tumor suppressor gene, and could be downregulated or dropped of expression via deletion, mutation, or advocate DNA methylation. Reduction of PTEN expression in activation of PI3K pathway leading to development of cancer. PTEN damage exists in about one third of breast cancer patients, including 1535-1536 to 48-hours.. Our study showed that the incidence of PTEN loss was 31. 63-11, that is in keeping with other reported results.. Previous reports suggested PTEN reduction and that PIK3CA mutation were mutually exclusive. MAPK family However, in 4 patients with H1047R mutations in our study, 3 patients were also found to possess no PTEN phrase. . This fact was once reported by Perez Tenorio et al last year. PI3K mutation was suggested to be connected with ER positivity, HER2 negativity and primary cyst size, of maybe not observed in our study. An analysis of our data showed that people with PI3K pathway activation had a statistically significant smaller median PFS than those with no PI3K pathway activation, confirming the reported conclusion that PI3K pathway activation can result in resistance to trastuzumab. Depending on the published preclinical reports, these patients should be vulnerable to lapatinib, a drug with another mechanism of action. Nevertheless, all people were treated with lapatinib and capecitabine within our study, and PI3K pathway activation was still linked with a lower clinical benefit rate and a lower overall response rate, which is consistent with of a smaller study reported by Cizkova et al.