BACKGROUND AND PURPOSE: Constitutive γ-H2AX expression might indicate disruption of the DNA damage repair pathway, genomic instability, or shortened telomeric ends. Here, we quantified expression of endogenous γ-H2AX and its downstream factor 53BP1 in a large number of breast cancer cell lines (n=54) and a node-negative breast cancer cohort that had not received adjuvant systemic treatment (n=122).
MATERIALS AND METHODS: Formalin fixed paraffin embedded breast cancer cell lines and tumors were immunohistochemically analyzed for γ-H2AX and 53BP1 expression, and related to cell line, patient and tumor characteristics and to disease progression.
RESULTS: In breast cancer cell lines, γ-H2AX positivity was associated with the triple negative/basal like subgroup (p=0.005), and with BRCA1 (p=0.011) or p53 (p=0.053) mutations. Specifically in triple negative breast cancer patients a high number of γ-H2AX foci indicated a significantly worse prognosis (p=0.006 for triple negative vs. p=0.417 for estrogen receptor (ER), progesterone receptor (PR) or HER2 positive patients). A similar association with disease progression was found for 53BP1. In a multivariate analysis with tumor size, grade, and triple negativity, only the interaction between triple negativity and γ-H2AX remained significant (p=0.002, Hazard Ratio=6.77, 95% CI=2.07-22.2).
CONCLUSIONS: Constitutive γ-H2AX and 53BP1 staining reveals a subset of patients with triple negative breast tumors that have a significantly poorer prognosis.
- Biomarkers, Tumor/metabolism
- Biopsy, Needle
- Breast Neoplasms/metabolism
- Cohort Studies
- DNA Damage/genetics
- DNA Repair/genetics
- Disease-Free Survival
- Gene Expression Regulation, Neoplastic
- Genetic Predisposition to Disease
- Intracellular Signaling Peptides and Proteins/metabolism
- Middle Aged
- Predictive Value of Tests
- Receptor, ErbB-2/metabolism
- Receptors, Progesterone/metabolism
- Survival Analysis
- Tissue Embedding
- Tumor Suppressor p53-Binding Protein 1