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

Abstract

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.

Tools to Guide Radiation Oncologists in the Management of DCIS

“…To assess the safety of the omission of RT in the low-risk DCIS, the ROMANCE randomized trial [22] integrated CPFs (age 50 years or older, margins ≥ 2 mm, size ≤ 2.5 cm, nuclear grade 1-2, and no necrosis) with biomolecular Luminal A-like features (positive hormonal receptors, HER2 negative, low . High expectations also come from genomic assays, namely Oncotype DCIS and DCISionRT [13,23,24].…”

“…The main ongoing trials dealing with genomic signatures in the DCIS setting are reported in Table 1. High expectations are placed not only on providing more reliable estimates of LR risk but also on predicting the response to RT, thus achieving a tailored approach [24].…”

Genetic Testing Enhances the Precision Diagnosis and Treatment of Breast Cancer

“…This review illustrated representative oncogenic mutations and aberrant expressions of certain genes that reflect clinical outcomes, therapeutic effects, and malignant biological properties. For HR-positive breast cancer patients in the early stage, MGA including Oncotype Dx, MammaPrint, RecurIndex, breast cancer index (BCI), EndoPredict, and Prosigna Prediction Analysis of Microarray 50 (PAM50) are all helpful candidates for precisely predicting clinical outcomes [9][10][11][12][13][14][15]. For patients with metastatic breast cancer, genetic tests that include specific genetic mutations and biomarkers for immunotherapy also help to identify therapeutic targets and monitor efficacy [16][17][18].…”

Editorial for “Feasibility of Quantitative MRI using 3D‐QALAS for Discriminating Immunohistochemical Status in Invasive Ductal Carcinoma of the Breast”

“…It is a lot of research in the area, most of it not introduced into clinical practice, but some of it will be of value. 8 Genetics, genomics, proteomics, and several other -omics are all being investigated. In order to use this in the future, we need a biopsy, or do we?…”

“…The second aspect of this is all the “‐omics” from molecular biology, this is not discussed in the article. It is a lot of research in the area, most of it not introduced into clinical practice, but some of it will be of value 8 . Genetics, genomics, proteomics, and several other –omics are all being investigated.…”