Quantitative immunohistochemical (IHC) assessment of ataxia-telangiectasia mutated (ATM) in estrogen receptor (ER) negative early breast cancer (BC).
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abstract
e21083 Background: ATM plays a key role in the cellular response to DNA damage and germline mutations are associated with a predisposition to BC. We evaluated the impact of ATM expression on outcomes in Stage I-III ER negative BC patients (pts). Methods: A tissue microarray was constructed from formalin-fixed paraffin-embedded specimens of ER negative Stage I-III BC pts from the Tom Baker Cancer Centre. ATM expression was assessed by quantitative fluorescence IHC using a rabbit anti-ATM monoclonal antibody (Epitomics) and the HistoRx AQUA platform. ATM expression index (EI) was calculated by the tumor cell to stroma expression ratio. Prognostic ability of ATM EI was explored univariately, and multivariately after adjusting for clinicopathological factors selected using algorithmic methods, with Cox regression methods. Results: Of 126 eligible pts treated from 1999-2004, 44.4% were HER2-neu + and 52.4% were triple negative. ATM EI was normalized using a logarithmic transformation. Univariately, higher ATM EI was associated with worse outcomes (Table). Multivariately, higher ATM EI remained significantly prognostic for recurrence-free survival (RFS) (HR=5.46, p=0.046), local RFS (HR=5.56, p=0.052), distant RFS (HR=4.38, p=0.080), but not overall survival (p=0.48). Conclusions: High ATM EI is associated with worse RFS in ER negative BC in this hypothesis-generating study. Validation of this finding is currently ongoing. [Table: see text]
