Clinical Significance and Genetic Characteristics in HER2 Low Expression Tumors of Hormone Receptor Positive Breast Cancer Patients

Abstract

BackgroundHuman epidermal growth factor receptor 2 (HER2) low expressed breast cancer was considered as a distinct subtype different from HER2 negative tumors. We investigated the clinicopathological features and recurrence score (RS) of HER2-low and HER2- patients and their prognostic value in hormone receptor (HR) positive breast cancer.MethodsA total of 2,099 HR-positive primary female breast cancer patients between Jan 2009 and Jan 2019 were collected and tumors with immunohistochemistry 1 + or 2 + with negative in situ hybridization results was defined as HER2 low. We retrospectively compared the clinical and genetical features of HER2-low (n = 1,732) and HER2- (n = 367) breast cancer and theirs impacts on disease-free survival (DFS).ResultsThe HER2 low tumors had a higher ratio of concurrent estrogen receptor (ER) high expression than HER2- patients both at protein level (ER > 90%: 78.2% vs 58.6%, p < 0.01) and mRNA level (Spearman R = 0.5 vs 0.3). Analysis about DFS showed no significant difference between HER2 negative and low subgroups (5-year DFS: 92.3% vs 93.3%, p = 0.83). However, RS range (cut-off: 18 and 30) didn’t maintain its predictive value in HER2 low patients (p = 0.11) unlike that in HER2- group (p = 0.003). Further research for respective gene suggested that proliferation related genes performed well in predicting DFS in HER2- patients but lost its value in HER2 low group (p for interaction < 0.01). Contrarily, higher HER2 module was associated with worse DFS only in HER2 low patients (p = 0.04).ConclusionOur study found that HER2 low expression couldn’t be a prognostic factor in HR + patients. HER2-low patients had a higher proportion of ER high expressed tumors than HER2- ones did. The 21-gene assay and its proliferation module might be less applicable to HER2-low patients compared with HER2- patients.