Open AccessClinicogenomic Radiotherapy Classifier Predicting the Need for Intensified Locoregional Treatment After Breast-Conserving Surgery for Early-Stage Breast Cancer
Author(s) -
Martin Sjöström,
S. Laura Chang,
Nick Fishbane,
Elai Davicioni,
Shuang G. Zhao,
Linda Hartman,
Erik Holmberg,
Felix Y. Feng,
Corey Speers,
Lori J. Pierce,
Per Malmström,
Mårten Fernö,
Per Karlsson
Publication year - 2019
Publication title -
journal of clinical oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 10.482
H-Index - 548
eISSN - 1527-7755
pISSN - 0732-183X
DOI - 10.1200/jco.19.00761
Subject(s) - medicine , breast cancer , cumulative incidence , breast conserving surgery , oncology , hazard ratio , adjuvant radiotherapy , radiation therapy , incidence (geometry) , stage (stratigraphy) , adjuvant , cancer , mastectomy , cohort , confidence interval , paleontology , physics , optics , biology
PURPOSE Most patients with early-stage breast cancer are treated with adjuvant radiotherapy (RT) after breast-conserving surgery (BCS) to prevent locoregional recurrence (LRR). However, no genomic tools are used currently to select the optimal RT strategy.METHODS We profiled the transcriptome of primary tumors on a clinical grade assay from the SweBCG91-RT trial, in which patients with node-negative breast cancer were randomly assigned to either whole-breast RT after BCS or no RT. We derived a new classifier, Adjuvant Radiotherapy Intensification Classifier (ARTIC), comprising 27 genes and patient age, in three publicly available cohorts, then independently validated ARTIC for LRR in 748 patients in SweBCG91-RT. We also compared previously published genomic signatures for ability to predict benefit from RT in SweBCG91-RT.RESULTS ARTIC was highly prognostic for LRR in patients treated with RT (hazard ratio [HR], 3.4; 95% CI, 2.0 to 5.9; P < .001) and predictive of RT benefit ( P interaction = .005). Patients with low ARTIC scores had a large benefit from RT (HR, 0.33 [95% CI, 0.21 to 0.52], P < .001; 10-year cumulative incidence of LRR, 6% v 21%), whereas those with high ARTIC scores benefited less from RT (HR, 0.73 [95% CI, 0.44 to 1.2], P = .23; 10-year cumulative incidence of LRR, 25% v 32%). In contrast, none of the eight previously published signatures were predictive of benefit from RT in SweBCG91-RT.CONCLUSION ARTIC identified women with a substantial benefit from RT as well as women with a particularly elevated LRR risk in whom whole-breast RT was not sufficiently effective and, thus, in whom intensified treatment strategies such as tumor-bed boost, and possibly regional nodal RT, should be considered. To our knowledge, ARTIC is the first classifier validated as predictive of benefit from RT in a phase III clinical trial with patients randomly assigned to receive or not receive RT.