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Article type: Research Article
Authors: Si, Pilei1 | Xu, Ye1 | Ouyang, Tao | Li, Jinfeng | Wang, Tianfeng | Fan, Zhaoqing | Fan, Tie | Lin, Benyao | Xie, Yuntao*
Affiliations: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Breast Center, Beijing Cancer Hospital and Institute, Peking University Cancer Hospital, Beijing 100142, China
Correspondence: [*] Corresponding author: Yuntao Xie, Breast Center, Beijing Cancer Hospital and Institute, Peking University Cancer Hospital, Beijing 100142, China, Tel./Fax: +86 1088196362; E-mail: zlxyt2@bjmu.edu.cn.
Note: [1] These authors contributed equally to this work.
Abstract: PURPOSE: To investigate the association between the HER2 germline mutation Ala270Ser (A270S), located in HER2 extracellular domain, and survival in breast cancer patients. METHODS: HER2 germline mutation A270S was identified in 5395 consecutive patients with operable primary breast cancer using direct Sanger sequencing analysis. Survival curves for patients with HER2 A270S mutation were compared using the Kaplan-Meier method with log-rank test. RESULTS: We identified that 31 cases carried HER2 germline mutation A270S in 5395 patients (0.6%, 31/5395). The HER2 A270S mutation was significantly associated with recurrence-free survival (RFS) and distant recurrence-free survival (DRFS) in the entire cohort of 5395 patients (RFS, unadjusted hazard ratio [HR] = 2.23; 95% confidence interval [CI] = 1.00–5.00; P= 0.045; DRFS, unadjusted HR = 2.80; 95% CI = 1.25–6.28; P= 0.009). Among the HER2-negative patients (n= 3825), those with the HER2 A270S mutation had a significantly worse RFS (unadjusted HR = 3.19; 95% CI = 1.42–7.16; P= 0.003) and DRFS (unadjusted HR = 3.98; 95% CI = 1.77–8.96; P< 0.001) than did those with wild type. Moreover, the A270S mutation remained an independent unfavorable factor for RFS and DRFS in the HER2-negative patients (RFS, HR = 3.30; 95% CI = 1.34–8.10; P= 0.009; DRFS, HR = 4.26; 95% CI = 1.73–10.47; P= 0.002). CONCLUSIONS: Breast cancer patients with the HER2 germline mutation A270S had a worse survival, especially in HER2-negative patients. Therefore, HER2-negative patients with a HER2 germline mutation A270S might be potential candidates for HER2-targeted therapy.
Keywords: Breast cancer, prognosis, HER2, germline mutation
DOI: 10.3233/CBM-170466
Journal: Cancer Biomarkers, vol. 23, no. 2, pp. 165-171, 2018
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