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22.01.2019 | Clinical trial

Prognostic effects of abnormal DNA damage response protein expression in breast cancer

verfasst von: Koung Jin Suh, Han Suk Ryu, Kyung-Hun Lee, Hyojin Kim, Ahrum Min, Tae-Yong Kim, Yaewon Yang, Han-Byoel Lee, Hyeong-Gon Moon, Sae-Won Han, Do-Youn Oh, Wonshik Han, In Ae Park, Dong-Young Noh, Seock-Ah Im

Erschienen in: Breast Cancer Research and Treatment | Ausgabe 1/2019

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Abstract

Purpose

We aimed to explore the expression of DNA damage response machinery proteins and their integrated prognostic value in different subgroups of breast cancer.

Methods

Expression of NBS1, BRCA1, BRCA2, ATM, and p53 was determined by immunohistochemistry in 419 surgically resected breast tumors.

Results

Loss of NBS1, BRCA1, ATM, and abnormal p53 expression was significantly associated with lower disease-free survival rates. Abnormal DNA damage response protein expression, defined as loss of any one of NBS1, BRCA1, ATM, and/or abnormal p53 expression, was observed in 258 of 399 evaluable cases (64.7%) and was significantly associated with higher tumor grade, larger tumor size, and ER-negative, and/or PR-negative status. Most patients with luminal B (86.1%), HER2-enriched (94.4%), and triple-negative (86.8%) breast cancers had abnormal DNA damage response protein expression. In contrast, abnormal DNA damage response protein expression was found in only 53.8% of luminal A tumors. Abnormal DNA damage response protein expression was associated with significantly lower 5-year disease-free survival rates in all patients (95.6% vs. 84.8%, p = 0.001), as well as in the luminal A subgroup (97.4% vs. 89.0%, p = 0.011). In multivariate analysis, abnormal DNA damage response protein expression remained an independent predictor of shorter disease-free survival for luminal A subtype (hazard ratio 3.14, 95% confidence interval 1.16–8.47; p = 0.024).

Conclusion

Abnormal DNA damage response protein expression is found in most luminal B and HER2-enriched breast cancers as frequently as in triple-negative breast cancer. In the luminal A subtype, abnormal DNA damage response protein expression is an independent prognostic marker.

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Titel: Prognostic effects of abnormal DNA damage response protein expression in breast cancer
verfasst von: Koung Jin Suh
Han Suk Ryu
Kyung-Hun Lee
Hyojin Kim
Ahrum Min
Tae-Yong Kim
Yaewon Yang
Han-Byoel Lee
Hyeong-Gon Moon
Sae-Won Han
Do-Youn Oh
Wonshik Han
In Ae Park
Dong-Young Noh
Seock-Ah Im
Publikationsdatum: 22.01.2019
Verlag: Springer US
Erschienen in: Breast Cancer Research and Treatment / Ausgabe 1/2019
Print ISSN: 0167-6806
Elektronische ISSN: 1573-7217
DOI: https://doi.org/10.1007/s10549-019-05128-9

Springer Medizin

Prognostic effects of abnormal DNA damage response protein expression in breast cancer