Molecular Signatures in Ductal Carcinoma In Situ (DCIS): A Systematic Review and Meta-Analysis.

CONTEXT: Adjuvant radiotherapy (RT) after breast-conserving surgery (BCS) for ductal carcinoma in situ (DCIS) is debated as benefits are inconstant. Molecular signatures for DCIS have been developed to stratify the risk of local recurrence (LR) and therefore guide the decision of RT. OBJECTIVE: To evaluate, in women with DCIS treated by BCS, the impact of adjuvant RT on LR according to the molecular signature risk stratification. METHODOLOGY: We conducted a systematic review and meta-analysis of five articles including women with DCIS treated by BCS and with a molecular assay performed to stratify the risk, comparing the effect of BCS and RT versus BCS alone on LR including ipsilateral invasive (InvBE) and total breast events (TotBE). RESULTS: The meta-analysis included 3478 women and evaluated two molecular signatures: Oncotype Dx DCIS (prognostic of LR), and DCISionRT (prognostic of LR and predictive of RT benefit). For DCISionRT, in the high-risk group, the pooled hazard ratio of BCS + RT versus BCS was 0.39 (95%CI 0.20-0.77) for InvBE and 0.34 (95%CI 0.22-0.52) for TotBE. In the low-risk group, the pooled hazard ratio of BCS + RT versus BCS was significant for TotBE at 0.62 (95%CI 0.39-0.99); however, it was not significant for InvBE (HR = 0.58 (95%CI 0.25-1.32)), Discussion: Molecular signatures are able to discriminate high- and low-risk women, high-risk ones having a significant benefit of RT in the reduction of invasive and in situ local recurrences, while in low-risk ones RT did not have a benefit for preventing invasive breast recurrence. The risk prediction of molecular signatures is independent of other risk stratification tools developed in DCIS, and have a tendency toward RT de-escalation. Further studies are needed to assess the impact on mortality.