%0 Journal Article
%T Association of ¦ÃH2AX at Diagnosis with Chemotherapy Outcome in Patients with Breast Cancer
%A Dat Nguyen
%A Eric C. Polley
%A Sherry X. Yang
%J Theranostics
%D 2017
%I Ivyspring International Publisher
%R 10.7150/thno.19102
%X ¦ÃH2AX plays a role in DNA damage response signaling and facilitates the repair of DNA double strand breaks. However, it remains unknown whether constitutive tumor ¦ÃH2AX expression is associated with treatment outcome in patients. ¦ÃH2AX status was detected in primary tumors from 24% of 826 patients with stage I, II and III breast cancer by immunohistochemistry; overall survival was analyzed by Kaplan-Meier method. At median follow-up of 176 months (range 13 - 282 months), we found substantial survival heterogeneity in ¦ÃH2AX-positive patients (P=0.002) among uniform treatment groups including radiation or endocrine therapy alone and no-treatment, as well as chemotherapy alone (being worst), in contrast to ¦ÃH2AX-negative patients (P=0.2). In the chemotherapy group (n=118), median survival was 63 months (95% confidence interval [CI], 29 - 83) in patients with ¦ÃH2AX-positive tumors compared with 170 months (95% CI 94 - 235) in those with ¦ÃH2AX-negative tumors (P=0.0017). ¦ÃH2AX remained a poor prognosis factor in the group by multivariable analysis (adjusted hazard ratio 2.12, P=0.009). Our data demonstrate that constitutive ¦ÃH2AX positivity is significantly associated with survival heterogeneity in patients among uniform treatment groups, and its expression at diagnosis independently predicts poor chemotherapy outcome in breast cancer.
%K breast cancer
%K chemotherapy
%K ¦ÃH2AX expression
%K overall survival
%K standard therapy.
%U http://www.thno.org/v07p0945.htm