Integration of a Radiosensitivity Molecular Signature into the Assessment of Local Recurrence Risk in Breast Cancer
Menée sur 343 patientes atteintes d'un cancer du sein et ayant reçu un traitement conservateur comportant une radiothérapie, cette étude évalue l'association entre une signature moléculaire permettant d'estimer la radiosensibilité de la tumeur et le risque de récidive locale
Abstract : Purpose/Objective: Recently, we developed RSI, a clinically-validated molecular signature that estimates tumor radiosensitivity. Here, we test whether integrating RSI with molecular subtype refines the classification of local recurrence risk in breast cancer
Methods and Materials : RSI and molecular subtype were evaluated in 343 patients treated with breast-conserving therapy including whole-breast RT plus/minus tumor bed boost (dose range, 45 – 72 Gy). The follow up for patients without recurrence was 10 years. Clinical endpoint was local recurrence-free survival (LRFS).
Results : While RSI did not uniformly predict for local recurrence across the entire cohort, combining RSI and molecular subtype identifies a subpopulation with an increased risk of local recurrence: triple negative (TN) and radioresistant (TN-R) (Ref –TN-R, HR=0.37 (0.15, 0.92) p=0.02). TN patients that were RSI-Sensitive/Intermediate (RSI-S/Int) had similar LR rates as LUM patients (HR=0.86 (0.47, 1.57) p=0.63). On multivariate analysis (MVA) combined RSI-Molecular Subtype (p=0.004), along with age (p=0.001) were the most significant predictors of LR. In contrast, integrating RSI into the LUM subtype did not identify additional risk groups. We hypothesized that RT dose escalation was impacting radioresistance in the LUM subtype and serving as a confounder. Indeed, increased RT dose decreased LR only in the LUM-R subset (HR = 0.23 (0.05, 0.98), p=0.03). On MVA, RT dose was an independent variable only in the LUMA/B-RR subset (HR=0.025 (0.001, 0.946), p=0.046), along with age (p=0.008), T stage (p=0.004) and chemotherapy (p=0.008).
Conclusions : Combined molecular subtype-RSI identifies a novel molecular sub-population (Triple Negative and Radioresistant) with an increased risk of local recurrence after BCT. We propose RSI-molecular subtype may be useful in guiding RT-based decisions in breast cancer.
International Journal of Radiation Oncology • Biology • Physics , résumé, 2014