HER2 somatic mutations S310F and V777L are associated with poor survival in breast cancer patients

Objective To assess the prognostic value of HER2 (human epidermal growth factor receptor-2) somatic mutations S310F and V777L in breast cancer patients. Methods HER2 somatic mutations S310F and V777L was screened in 338 consecutive patients with operable primary breast cancer using direct Sanger sequencing analysis. Results A total of 12 carriers of HER2 gene S310F and V777L mutations were found, 10 were HER2-negative and 2 were HER2-positive . The median follow-up was 43 months (range from 1 to 61 months).4 were found with local or distant metastasis, and all were HER2-negative patients. Survival analysis found significantly lower survival rates in patients with S310F and V777L mutations than in non-carriers (RFS, unadjusted hazard ratio [HR]: 5.89, 95% confidence interval [CI]: 1.96-17.71, P<0.001; DRFS, unadjusted HR: 5.53, 95%CI: 1.56-19.55, P=0.003) and this difference was more manifest in the HER2-negative patients (RFS, unadjusted HR: 8.93, 95%CI: 2.79-28.62, P<0.001; DRFS, unadjusted HR: 9.89, 95%CI: 2.54-38.49, P<0.001). HER2 somatic mutations S310F and V777L are independent predictors of poor prognosis in breast cancer. Conclusion The prognosis of breast cancer patients carrying HER2 somatic mutations S310F and V777L is significantly worse than that of non-carriers, especially in HER2-negative patients. Key words: Breast neoplasms; Receptor, epidermal growth factor; Somatic mutation; Survival analysis