HER2 exon 27 mutations predict worse survival of breast cancer patients, especially in HER2-negative patients

Abstract

The aims of this study were to assess the prognostic value of the HER2 exon 27 mutations in breast cancer patients. Genomic DNA was isolated from peripheral blood leukocytes, and then HER2 exon 27 mutations were detected by direct sequencing. Survival curves were estimated by Kaplan–Meier curves and the differences between the curves were compared by log-rank tests. A total cohort of 892 female patients with operable primary breast cancer was included in this study. The median follow-up was 47 months. Of these 892 patients, 3.7% (33/892) had HER2 exon 27 mutations. Patients with the HER2 exon 27 mutations had a significant worse recurrence-free survival (RFS, unadjusted hazard ratio [HR] 2.42; 95% CI: 1.05–5.58; P = 0.032) and distant recurrence-free survival (DRFS, unadjusted HR 2.81; 95% CI: 1.21–6.50; P = 0.012) than the patients with the wild-type exon 27. Among the 673 patients with negative HER2 expression, 24 mutants were found. Patients with the HER2 mutations showed a worse RFS (unadjusted HR 5.08; 95% CI: 2.14–12.02; P < 0.001) and DRFS (unadjusted HR 5.62; 95% CI: 2.36–13.40; P < 0.001) than those patients with the wild-type exon 27. Furthermore, the mutations remained as unfavorable independent predictors for RFS and DRFS. Breast cancer patients with HER2 exon 27 mutations have a worse survival, especially in HER2-negative patients. HER2-negative patients with HER2 exon 27 mutations are potential subgroup of breast cancer patients benefiting from HER2-targeted therapy in future.

We found breast cancer patients with HER2 exon 27 mutations had a worse survival, especially in HER2-negative patients. The HER2 exon 27 mutations can differentiate the subgroup with worse survival from HER2-negative patients and might be a novel therapeutic target for HER2-negative patients in future.

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