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HER2 somatic mutations are associated with poor survival in HER2‐negative breast cancers

2017; Wiley; Volume: 108; Issue: 4 Linguagem: Inglês

10.1111/cas.13182

1349-7006

Tonghui Wang, Ye Xu, Shuyan Sheng, Hua Yuan, Tao Ouyang, Jinfeng Li, Tianfeng Wang, Zhaoqing Fan, Tie Fan, Benyao Lin, Yuntao Xie,

Glycosylation and Glycoproteins Research

It is well documented that human epidermal growth factor receptor 2 ( HER 2) overexpression/amplification is associated with poor survival in breast cancer patients. However, it is largely unknown whether HER 2 somatic mutations are associated with survival in HER 2‐negative breast cancer patients. Here, we identified HER 2 somatic mutations in tumors from 1348 unselected breast cancer patients by sequencing the entire HER 2 coding region. All of these mutations were tested for in corresponding blood samples to determine whether they were somatic or germline mutations. We further investigated the associations between HER 2 somatic mutations and recurrence‐free survival and distant recurrence‐free survival in this cohort of patients. We found that 27 of 1348 (2.0%) of these patients carried a HER 2 somatic mutation. In vitro experiments indicated that some of the novel mutations and those with unknown functions increased HER 2 activity. HER 2 status was available for 1306 patients, and the HER 2 somatic mutation rates in HER 2‐positive ( n = 353) and HER 2‐negative breast cancers ( n = 953) were 1.4% and 2.3%, respectively. Among the HER 2‐negative patients, those with a HER 2 somatic mutation had a significantly worse recurrence‐free survival (unadjusted hazard ratio = 2.67; 95% confidence interval, 1.25–5.72, P = 0.002) and distant recurrence‐free survival (unadjusted hazard ratio = 2.50; 95% confidence interval, 1.10–5.68, P = 0.004) than those with wild‐type HER 2 . Taken together, our findings suggested that HER 2 somatic mutations occur at a higher frequency in HER 2‐negative breast cancer, and HER 2‐negative breast cancer patients with these mutations have poor survival. Therefore, HER 2‐negative patients with a HER 2 somatic mutation are potentially good candidates for HER 2‐targeted therapy.