Open AccessHER2 somatic mutations are associated with poor survival in HER2‐negative breast cancers
Author(s) -
Wang Tonghui,
Xu Ye,
Sheng Shuyan,
Yuan Hua,
Ouyang Tao,
Li Jinfeng,
Wang Tianfeng,
Fan Zhaoqing,
Fan Tie,
Lin Benyao,
Xie Yuntao
Publication year - 2017
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.13182
Subject(s) - somatic cell , germline mutation , hazard ratio , breast cancer , germline , medicine , oncology , confidence interval , mutation , cancer , biology , genetics , gene
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.