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Loss of ataxia-telangiectasia mutated protein expression correlates with poor prognosis but benefits from anthracycline-containing adjuvant chemotherapy in breast cancer : 유방암 환자에서 ataxia-telangiectasia mutated 단백의 소실과 예후 및 안트라싸이클린 계열 보조항암화학치료의 효과의 연관성에 관한 연구
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- Authors
- Advisor
- 임석아
- Major
- 의과대학 의학과
- Issue Date
- 2016-08
- Publisher
- 서울대학교 대학원
- Keywords
- ataxia-telangiectasia mutated (ATM) ; p53 ; immunohistochemistry ; prognosis ; anthracycline ; PARP-1 inhibitor
- Description
- 학위논문 (석사)-- 서울대학교 대학원 : 의학과 분자종양의학, 2016. 8. 임석아.
- 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.
- Language
- English
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