title: Loss of ataxia-telangiectasia-mutated protein expression correlates with poor prognosis but benefits from anthracycline-containing adjuvant chemotherapy in breast cancer.
abstract: We investigated the correlation of ataxia-telangiectasia-mutated (ATM) protein expression with clinicopathological features and prognosis in patients with breast cancer. ATM expression was determined by immunohistochemistry in 420 surgically resected breast tumors. 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. 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.
authors.affiliation: Department of Internal Medicine, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul, 110-744, Korea.
authors.forename: Koung Jin
authors.initials: KJ
authors.lastname: Suh
authors.affiliation: Department of Pathology, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul, 110-744, Korea.
authors.forename: Han Suk
authors.initials: HS
authors.lastname: Ryu
authors.affiliation: Department of Internal Medicine, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul, 110-744, Korea. kyunghunlee@snu.ac.kr.|Cancer Research Institute, Seoul National University, 101 Daehak-ro, Jongno-gu, Seoul, 110-779, Korea. kyunghunlee@snu.ac.kr.
authors.forename: Kyung-Hun
authors.initials: KH
authors.lastname: Lee
authors.affiliation: Department of Pathology, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul, 110-744, Korea.
authors.forename: Hyojin
authors.initials: H
authors.lastname: Kim
authors.affiliation: Cancer Research Institute, Seoul National University, 101 Daehak-ro, Jongno-gu, Seoul, 110-779, Korea.
authors.forename: Ahrum
authors.initials: A
authors.lastname: Min
authors.affiliation: Department of Internal Medicine, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul, 110-744, Korea.|Cancer Research Institute, Seoul National University, 101 Daehak-ro, Jongno-gu, Seoul, 110-779, Korea.
authors.forename: Tae-Yong
authors.initials: TY
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul, 110-744, Korea.
authors.forename: Yaewon
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Surgery, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul, 110-744, Korea.|Cancer Research Institute, Seoul National University, 101 Daehak-ro, Jongno-gu, Seoul, 110-779, Korea.
authors.forename: Hyeong-Gon
authors.initials: HG
authors.lastname: Moon
authors.affiliation: Department of Internal Medicine, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul, 110-744, Korea.|Cancer Research Institute, Seoul National University, 101 Daehak-ro, Jongno-gu, Seoul, 110-779, Korea.
authors.forename: Sae-Won
authors.initials: SW
authors.lastname: Han
authors.affiliation: Department of Internal Medicine, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul, 110-744, Korea.|Cancer Research Institute, Seoul National University, 101 Daehak-ro, Jongno-gu, Seoul, 110-779, Korea.
authors.forename: Do-Youn
authors.initials: DY
authors.lastname: Oh
authors.affiliation: Department of Surgery, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul, 110-744, Korea.|Cancer Research Institute, Seoul National University, 101 Daehak-ro, Jongno-gu, Seoul, 110-779, Korea.
authors.forename: Wonshik
authors.initials: W
authors.lastname: Han
authors.affiliation: Department of Pathology, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul, 110-744, Korea.
authors.forename: In Ae
authors.initials: IA
authors.lastname: Park
authors.affiliation: Department of Surgery, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul, 110-744, Korea.|Cancer Research Institute, Seoul National University, 101 Daehak-ro, Jongno-gu, Seoul, 110-779, Korea.
authors.forename: Dong-Young
authors.initials: DY
authors.lastname: Noh
authors.affiliation: Department of Internal Medicine, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul, 110-744, Korea. moisa@snu.ac.kr.|Cancer Research Institute, Seoul National University, 101 Daehak-ro, Jongno-gu, Seoul, 110-779, Korea. moisa@snu.ac.kr.
authors.forename: Seock-Ah
authors.initials: SA
authors.lastname: Im
mesh_terms: D018943:Anthracyclines / Q000008:administration & dosage* / Q000627:therapeutic use; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000627:therapeutic use; D064007:Ataxia Telangiectasia Mutated Proteins / Q000378:metabolism*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D018572:Disease-Free Survival; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008207:Lymphatic Metastasis; D008875:Middle Aged; D060787:Neoplasm Grading; D011379:Prognosis; D016019:Survival Analysis; D016896:Treatment Outcome; D047368:Tumor Burden
chemical_list: D018943:Anthracyclines; D000903:Antibiotics, Antineoplastic; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins
keywords: Anthracycline; Ataxia-telangiectasia-mutated (ATM); Immunohistochemistry; PARP-1 inhibitor; Prognosis; p53