Development and validation of a gene profile predicting benefit of postmastectomy radiotherapy in patients with high-risk breast cancer: A study of gene expression in the DBCG82bc cohort: Tramm T, Mohammed H, Myhre S, et al (Aarhus Univ Hosp, Denmark; Univ of Oslo, Norway; Oslo Univ Hosp, Norway) Clin Cancer Res 20:5272-5280, 2014

Document Type

Journal Article

Publication Date

1-1-2015

Journal

Breast Diseases

Volume

26

Issue

2

DOI

10.1016/j.breastdis.2015.04.032

Abstract

Purpose. -To identify genes predicting benefit of radiotherapy in patients with high-risk breast cancer treated with systemic therapy and randomized to receive or not receive postmastectomy radiotherapy (PMRT). Experimental Design. -The study was based on the Danish Breast Cancer Cooperative Group (DBCG82bc) cohort. Gene-expression analysis was performed in a training set of frozen tumor tissue from 191 patients. Genes were identified through the Lasso method with the endpoint being locoregional recurrence (LRR). A weighted gene-expression index (DBCG-RT profile) was calculated and transferred to quantitative real-time PCR (qRT-PCR) in corresponding formalin-fixed, paraffin- embedded (FFPE) samples, before validation in FFPE from 112 additional patients. Results. -Seven genes were identified, and the derived DBCG-RT profile divided the 191 patients into "high LRR risk" and "low LRR risk" groups. PMRT significantly reduced risk of LRR in "high LRR risk" patients, whereas ±low LRR risk" patients showed no add ional reduction in LRR rate. Technical transfer of the DBCG-RT profile to FFPE/ qRT-PCR was successful, and the predictive impact was successfully validated in another 112 patients. Conclusions. -A DBCG-RT gene profile was identified and validated, identifying patients with very low risk of LRR and no benefit from PMRT. The profile may provide a method to individualize treatment with PMRT.

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