ATM-Chk2 network is critical for genomic stability and its deregulation may influence breast cancer pathogenesis. We investigated ATM and Chk2 protein levels in two cohorts [cohort 1 (n=1650) and cohort 2 (n= 252)]. ATM and Chk2 mRNA expression was evaluated in the Metabric cohort (n=1950). Low nuclear ATM protein level was significantly associated with aggressive breast cancer including larger size tumours, higher tumour grade, higher mitotic index, pleomorphism , tumour type , lymphovascular invasion, ER- , PR-, AR-, triple negative and basal-like phenotypes (ps<0.05). BRCA1 negative, low XRCC1, low SMUG1, high FEN1, high MIB1, p53 mutants, low MDM2, low Bcl-2, low p21, low Bax, high CDK1 and low Chk2 were also more frequent in tumours with low nuclear ATM level (ps<0.05). Low ATM protein level was significantly associated with poor survival including in patients with ER- negative tumours who received adjuvant anthracycline or CMF based adjuvant chemotherapy (ps<0.05). Low nuclear Chk2 protein was likely in ER-/PR-/AR-, HER- 2 positive, BRCA1 negative, low XRCC1, low SMUG1, low APE1, low polβ, low DNA-PKcs, low ATM, low Bcl-2 and low TOPO2A tumours (p<0.05). In patients with ER+ tumours who received endocrine therapy or ER- negative tumours who received chemotherapy, nuclear Chk2 levels did not significantly influence survival. In p53 mutant tumours, low ATM (p<0.000001) or high Chk2 (p<0.01) was associated with poor survival. When investigated together, low ATM/high Chk2 tumours have the worst survival (p=0.0033). Our data suggests that ATM-Chk2 levels in sporadic breast cancer may have prognostic and predictive significance.