PURPOSE: Local recurrence and distant failure after adjuvant radiation therapy for @entity0 remain significant clinical problems, incompletely predicted by conventional clinicopathologic markers. We had previously identified microRNA-139-5p and microRNA-1274a as key regulators of @entity0 radiation response in  vitro. The purpose of this study was to investigate standard clinicopathologic markers of local recurrence in a contemporary series and to establish whether putative target genes of microRNAs involved in DNA repair and cell cycle control could better predict radiation therapy response in  vivo. METHODS AND MATERIALS: With institutional ethics board approval, local recurrence was measured in a contemporary, prospectively collected series of 458 @entity1 treated with radiation therapy after breast-conserving surgery. Additionally, independent publicly available mRNA/microRNA microarray expression datasets totaling >1000 early-stage @entity0 @entity1 , treated with adjuvant radiation therapy, with >10  years of follow-up, were analyzed. The expression of putative microRNA target biomarkers- @entity14583 , @entity40112 , @entity44300 , @entity20127 , @entity22237 , and @entity12656 -were correlated with standard clinicopathologic variables using 2-sided nonparametric tests, and to local/distant relapse and survival using Kaplan-Meier and Cox regression analysis. RESULTS: We found a low rate of isolated local recurrence (1.95%) in our modern series, and that few clinicopathologic variables (such as @entity3 ) were significantly predictive. In multiple independent datasets (n>1000), however, high expression of @entity44300 , @entity14583 , @entity40112 , and @entity20127 significantly correlated with local recurrence, survival, or both in univariate and multivariate analyses (P<.001). Low @entity12656 expression significantly correlated with local recurrence (multivariate, P=.008). Additionally, @entity44300 , @entity20127 , and @entity22237 may be predictive, being prognostic in radiation therapy-treated @entity1 but not in untreated matched control individuals (n=107; P<.05). CONCLUSIONS: Biomarkers of DNA repair and cell cycle control can identify @entity1 at high risk of treatment failure in those receiving radiation therapy for early @entity0 in independent cohorts. These should be further investigated prospectively, especially @entity14583 and @entity20127 , for which targeted therapies are available.

MicroRNA-Related DNA Repair/Cell-Cycle Genes Independently Associated With Relapse After Radiation Therapy for Early XXXX .

@entity1 :: ('9606', 'Species') :: ['patients'] @entity20127 :: ('6502', 'Gene') :: ['SKP2'] @entity0 :: ('MESH:D001943', 'Disease') :: ['breast cancer'] @entity14583 :: ('7153', 'Gene') :: ['TOP2A'] @entity3 :: ('MESH:D009362', 'Disease') :: ['lymphovascular invasion'] @entity40112 :: ('10721', 'Gene') :: ['POLQ'] @entity12656 :: ('5896', 'Gene') :: ['RAG1'] @entity22237 :: ('10769', 'Gene') :: ['PLK2'] @entity44300 :: ('8438', 'Gene') :: ['RAD54L']
@entity0 :: (MESH:D001943,Disease) :: ['Breast Cancer']
