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22.01.2019 | Clinical trial | Ausgabe 1/2019

Breast Cancer Research and Treatment 1/2019

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

Zeitschrift:
Breast Cancer Research and Treatment > Ausgabe 1/2019
Autoren:
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
Wichtige Hinweise

Electronic supplementary material

The online version of this article (https://​doi.​org/​10.​1007/​s10549-019-05128-9) contains supplementary material, which is available to authorized users.

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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Zusatzmaterial
Supplementary material 1 (DOC 52 KB)
10549_2019_5128_MOESM1_ESM.doc
Literatur
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