PURPOSE: Recently, we developed @entity41060 ( @entity41060 ), a clinically validated molecular signature that estimates @entity5 @entity41060 . In the present study, we tested whether integrating @entity41060 with the molecular subtype refines the classification of local recurrence (LR) risk in @entity0 . METHODS AND MATERIALS: @entity41060 and molecular subtype were evaluated in 343 @entity1 treated with breast-conserving therapy that included whole-breast radiation therapy with or without a @entity5 bed boost (dose range 45-72  Gy). The follow-up period for @entity1 without recurrence was 10  years. The clinical endpoint was LR-free survival. RESULTS: Although @entity41060 did not uniformly predict for LR across the entire cohort, combining @entity41060 and the molecular subtype identified a subpopulation with an increased risk of LR: @entity549 ( @entity549 ) and radioresistant (reference @entity549 -radioresistant, hazard ratio [HR] 0.37, 95% confidence interval [CI] 0.15-0.92, P=.02). @entity549 @entity1 who were @entity41060 -sensitive/intermediate had LR rates similar to those of luminal (LUM) @entity1 (HR 0.86, 95% CI 0.47-1.57, P=.63). On multivariate analysis, combined @entity41060 and molecular subtype (P=.004) and age (P=.001) were the most significant predictors of LR. In contrast, integrating @entity41060 into the LUM subtype did not identify additional risk groups. We hypothesized that radiation dose escalation was affecting radioresistance in the LUM subtype and serving as a confounder. An increased radiation dose decreased LR only in the luminal-resistant (LUM-R) subset (HR 0.23, 95% CI 0.05-0.98, P=.03). On multivariate analysis, the radiation dose was an independent variable only in the LUMA/B-RR subset (HR 0.025, 95% CI 0.001-0.946, P=.046), along with age (P=.008), T stage (P=.004), and chemotherapy (P=.008). CONCLUSIONS: The combined molecular subtype- @entity41060 identified a novel molecular subpopulation ( @entity549 and radioresistant) with an increased risk of LR after breast-conserving therapy. We propose that the combination of @entity41060 and molecular subtype could be useful in guiding radiation therapy-based decisions in @entity0 .

Integration of a Radiosensitivity Molecular Signature Into the Assessment of Local Recurrence Risk in XXXX .

@entity1 :: ('9606', 'Species') :: ['patients'] @entity0 :: ('MESH:D001943', 'Disease') :: ['breast cancer'] @entity5 :: ('MESH:D009369', 'Disease') :: ['tumor'] @entity549 :: ('MESH:D064726', 'Disease') :: ['triple negative', 'TN'] @entity41060 :: ('MESH:C565848', 'Disease') :: ['RSI', 'radiosensitivity']
@entity0 :: (MESH:D001943,Disease) :: ['Breast Cancer']
