Loss of ataxia-telangiectasia mutated protein expression correlates with poor prognosis but benefits from anthracycline-containing adjuvant chemotherapy in breast cancer

Abstract

Purpose: We investigated the correlation of ataxia-telangiectasia mutated (ATM) protein expression with clinicopathological features and prognosis in patients with breast cancer. Methods: ATM expression was determined by immunohistochemistry in 420 surgically resected breast tumors. Results: ATM loss was observed in 126/407 evaluable cases (31.0%), and was significantly associated with larger tumor size, lymph node metastasis, higher tumor grade, and ER- and/or PR-negative status. ATM loss was also associated with significantly lower disease-free survival rates than those in patients with intact ATM (5-year disease-free survival rate 81.2% vs. 90.7%, p = 0.015). In multivariate analysis, ATM loss combined with abnormal p53 expression was an independent predictor of shorter disease-free survival (hazard ratio [HR] 3.48

95% confidence interval [CI], 1.48 - 8.17, p = 0.004). A tendency towards a poorer prognosis was observed for tumoral ATM loss alone, although statistical significance was not reached (HR 1.74

95% CI 0.95 - 3.20

p = 0.075). In subgroup analysis, ATM loss was associated with shorter disease-free survival in patients who did not receive adjuvant anthracycline chemotherapy (5-year disease-free survival rate 92.7% in intact ATM group vs. 68.1% in ATM loss group, p = 0.002), but this poor prognosis was overcome in patients who did (5-year disease-free survival rate 89.8% vs. 84.4%, p = 0.243), suggesting more benefit from anthracycline-based chemotherapy. Conclusion: Tumors with loss of ATM expression have a poor prognosis and their prognoses are dependent on the use of adjuvant anthracycline. ATM loss might be a practical tool for predicting benefits from anthracycline-based adjuvant therapy.