TY - JOUR
T1 - Development and Validation of a Genomic Profile for the Omission of Local Adjuvant Radiation in Breast Cancer
AU - Sjöström, Martin
AU - Fyles, Anthony
AU - Liu, Fei Fei
AU - McCready, David
AU - Shi, Wei
AU - Rey-Mcintyre, Katrina
AU - Chang, S. Laura
AU - Feng, Felix Y.
AU - Speers, Corey W.
AU - Pierce, Lori J.
AU - Holmberg, Erik
AU - Fernö, Mårten
AU - Malmström, Per
AU - Karlsson, Per
PY - 2023/3/10
Y1 - 2023/3/10
N2 - PURPOSEAdjuvant radiotherapy (RT) is used for women with early-stage invasive breast cancer treated with breast-conserving surgery. However, some women with low risk of recurrence may safely be spared RT. This study aimed to identify these women using a molecular-based approach.METHODSWe analyzed two randomized trials of women with node-negative invasive breast cancer to ± RT following breast-conserving surgery: SweBCG91-RT (stage I-II, no adjuvant systemic therapy) and Princess Margaret (age 50 years or older, T1-T2, adjuvant tamoxifen). Transcriptome-wide profiling was performed (Affymetrix Human Exon 1.0 ST microarray). Patients with estrogen receptor-positive/human epidermal growth factor receptor 2-negative tumors and with gene expression data were included. The SweBCG91-RT cohort was divided into training (N = 243) and validation (N = 354) cohorts. A 16-gene signature named Profile for the Omission of Local Adjuvant Radiation (POLAR) was trained to predict locoregional recurrence (LRR) using elastic net regression. POLAR was then validated in the SweBCG91-RT validation cohort and the Princess Margaret cohort (N = 132).RESULTSPatients categorized as POLAR low-risk without RT had a 10-year LRR of 6% (95% CI, 2 to 16) and 7% (0 to 27) in SweBCG91-RT and Princess Margaret cohorts, respectively. There was no significant benefit from RT in POLAR low-risk patients (hazard ratio [HR], 1.1 [0.39 to 3.4], P =.81, and HR, 1.5 [0.14 to 16], P =.74, respectively). Patients categorized as POLAR high-risk had a significant decreased risk of LRR with RT (HR, 0.43 [0.24 to 0.78], P =.0055, and HR, 0.25 [0.07 to 0.92], P =.038, respectively). An exploratory analysis testing for interaction between RT and POLAR in the combined validation cohort was performed (P =.066).CONCLUSIONThe novel POLAR genomic signature on the basis of LRR biology may identify patients with a low risk of LRR despite not receiving RT, and thus may be candidates for RT omission.
AB - PURPOSEAdjuvant radiotherapy (RT) is used for women with early-stage invasive breast cancer treated with breast-conserving surgery. However, some women with low risk of recurrence may safely be spared RT. This study aimed to identify these women using a molecular-based approach.METHODSWe analyzed two randomized trials of women with node-negative invasive breast cancer to ± RT following breast-conserving surgery: SweBCG91-RT (stage I-II, no adjuvant systemic therapy) and Princess Margaret (age 50 years or older, T1-T2, adjuvant tamoxifen). Transcriptome-wide profiling was performed (Affymetrix Human Exon 1.0 ST microarray). Patients with estrogen receptor-positive/human epidermal growth factor receptor 2-negative tumors and with gene expression data were included. The SweBCG91-RT cohort was divided into training (N = 243) and validation (N = 354) cohorts. A 16-gene signature named Profile for the Omission of Local Adjuvant Radiation (POLAR) was trained to predict locoregional recurrence (LRR) using elastic net regression. POLAR was then validated in the SweBCG91-RT validation cohort and the Princess Margaret cohort (N = 132).RESULTSPatients categorized as POLAR low-risk without RT had a 10-year LRR of 6% (95% CI, 2 to 16) and 7% (0 to 27) in SweBCG91-RT and Princess Margaret cohorts, respectively. There was no significant benefit from RT in POLAR low-risk patients (hazard ratio [HR], 1.1 [0.39 to 3.4], P =.81, and HR, 1.5 [0.14 to 16], P =.74, respectively). Patients categorized as POLAR high-risk had a significant decreased risk of LRR with RT (HR, 0.43 [0.24 to 0.78], P =.0055, and HR, 0.25 [0.07 to 0.92], P =.038, respectively). An exploratory analysis testing for interaction between RT and POLAR in the combined validation cohort was performed (P =.066).CONCLUSIONThe novel POLAR genomic signature on the basis of LRR biology may identify patients with a low risk of LRR despite not receiving RT, and thus may be candidates for RT omission.
U2 - 10.1200/JCO.22.00655
DO - 10.1200/JCO.22.00655
M3 - Article
C2 - 36599119
AN - SCOPUS:85149212437
SN - 0732-183X
VL - 41
SP - 1533
EP - 1540
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 8
ER -
