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. 2010 Dec 1;16(23):5796-804.
doi: 10.1158/1078-0432.CCR-10-0292.

DNA repair protein biomarkers associated with time to recurrence in triple-negative breast cancer

Brian M Alexander  1 , Kam Sprott, D Allan Farrow, XiaoZhe Wang, Alan D D'Andrea, Stuart J Schnitt, Laura C Collins, David T Weaver, Judy E Garber
Affiliations

DNA repair protein biomarkers associated with time to recurrence in triple-negative breast cancer

Brian M Alexander et al. Clin Cancer Res. .

Abstract

Purpose: To evaluate the prognostic utility of immunohistochemical assessment of key proteins in multiple DNA repair pathways in triple-negative breast cancer (TNBC; estrogen receptor negative, progesterone receptor negative, and HER2/neu negative by immunohistochemistry).

Experimental design: Archived clinically annotated tumor specimens from 112 women with TNBC were immunostained with antibodies against DNA repair proteins and scored using digital image analysis. The cohort was divided into training and test sets for development of a multiantibody model. Scores were combined with clinical data to assess association with outcome.

Results: Low XPF (P = 0.005), pMK2 (P = 0.01), MLH; P = 0.002), and FANCD2 (P = 0.001) were each associated with shorter time to recurrence (TTR) in univariate analysis. A 4-antibody model could segregate high-risk and low-risk groups on the basis of TTR in both the training (relative risk [RR] = 3.52; P = 9.05E-07) and test (RR 2.67; P = 0.019) cohorts.

Conclusions: DNA repair proteins may be useful as prognostic markers in TNBC. Further study in larger, uniformly treated cohorts with additional clinical parameters is warranted.

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Figures

Figure 1
Figure 1. Immunohistochemistry patterns for the several DNA repair antibodies in one triple negative breast tumor
Figure 2
Figure 2. Inter and intra-patient immunohistochemical scoring variation
For each antibody, the X axis represents the sorted patient ranks according to mean score among the triplicate core specimens while the Y axis represents the immunohistochemical score. Error bars display the intra patient variability between each of the three cores for each individual sample.
Figure 3
Figure 3. Kaplan-Meier plot for Time to Recurrence According to High Versus Low Recurrence Risk Group as Defined by the Four-Antibody Model in the Training Set
Figure 4
Figure 4. Kaplan-Meier plot for Time to Recurrence According to High Versus Low Recurrence Risk Group as Defined by the Four-Antibody Model in the Test Set
See this image and copyright information in PMC

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