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Development and Validation of a Genomic Profile for the Omission of Local Adjuvant Radiation in Breast Cancer

Sjöström, Martin LU ; Fyles, Anthony ; Liu, Fei Fei ; McCready, David ; Shi, Wei ; Rey-Mcintyre, Katrina ; Chang, S. Laura ; Feng, Felix Y. ; Speers, Corey W. and Pierce, Lori J. , et al. (2023) In Journal of Clinical Oncology 41(8). p.1533-1540
Abstract

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... (More)

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.

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type
Contribution to journal
publication status
published
subject
in
Journal of Clinical Oncology
volume
41
issue
8
pages
8 pages
publisher
American Society of Clinical Oncology
external identifiers
  • scopus:85149212437
  • pmid:36599119
ISSN
0732-183X
DOI
10.1200/JCO.22.00655
language
English
LU publication?
yes
id
e9f9e53f-69dc-4cd1-bbce-7a8e47498b47
date added to LUP
2024-01-12 13:27:42
date last changed
2024-04-27 08:50:50
@article{e9f9e53f-69dc-4cd1-bbce-7a8e47498b47,
  abstract     = {{<p>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.</p>}},
  author       = {{Sjöström, Martin and Fyles, Anthony and Liu, Fei Fei and McCready, David and Shi, Wei and Rey-Mcintyre, Katrina and Chang, S. Laura and Feng, Felix Y. and Speers, Corey W. and Pierce, Lori J. and Holmberg, Erik and Fernö, Mårten and Malmström, Per and Karlsson, Per}},
  issn         = {{0732-183X}},
  language     = {{eng}},
  month        = {{03}},
  number       = {{8}},
  pages        = {{1533--1540}},
  publisher    = {{American Society of Clinical Oncology}},
  series       = {{Journal of Clinical Oncology}},
  title        = {{Development and Validation of a Genomic Profile for the Omission of Local Adjuvant Radiation in Breast Cancer}},
  url          = {{http://dx.doi.org/10.1200/JCO.22.00655}},
  doi          = {{10.1200/JCO.22.00655}},
  volume       = {{41}},
  year         = {{2023}},
}