Validation of a breast cancer assay for radiotherapy omission : an individual participant data meta-analysis
(2025) In Journal of the National Cancer Institute 117(3). p.486-495- Abstract
Background: There are currently no molecular tests to identify individual breast cancers where radiotherapy (RT) offers no benefit. Profile for the Omission of Local Adjuvant Radiotherapy (POLAR) is a 16-gene molecular signature developed to identify low-risk cancers where RT will not further reduce recurrence rates. Methods: An individual participant data meta-analysis was performed in 623 patients of node-negative estrogen receptor–positive and HER2-negative early breast cancer enrolled in 3 RT randomized trials for whom primary tumor material was available for analysis. A Cox proportional hazards model on time to locoregional recurrence was used to test the interaction between POLAR score and RT. Results: A total of 429 (69%)... (More)
Background: There are currently no molecular tests to identify individual breast cancers where radiotherapy (RT) offers no benefit. Profile for the Omission of Local Adjuvant Radiotherapy (POLAR) is a 16-gene molecular signature developed to identify low-risk cancers where RT will not further reduce recurrence rates. Methods: An individual participant data meta-analysis was performed in 623 patients of node-negative estrogen receptor–positive and HER2-negative early breast cancer enrolled in 3 RT randomized trials for whom primary tumor material was available for analysis. A Cox proportional hazards model on time to locoregional recurrence was used to test the interaction between POLAR score and RT. Results: A total of 429 (69%) patients’ tumors had a high POLAR score, and 194 (31%) had a low score. Patients with high POLAR score had, in the absence of RT, a 10-year cumulative incidence of locoregional recurrence (20%, 95% confidence interval [CI] = 15% to 26%, vs 5%, [CI] 2% to 11%) for those with a low score. Patients with a high POLAR score had a large benefit from RT (hazard ratio [HR] for RT vs no RT = 0.37, 95% CI = 0.23 to 0.60; P < .001). In contrast, there was no evidence of benefit from RT for patients with a low POLAR score (HR = 0.92, 95% CI = 0.42 to 2.02; P = .832). The test for interaction between RT and POLAR was statistically significant (P = .022). Conclusions: POLAR is not only prognostic for locoregional recurrence but also predictive of benefit from RT in selected patients. Patients aged 50 years and older with estrogen receptor–positive and HER2-negative disease and a low POLAR score could consider omitting adjuvant RT. Further validation in contemporary clinical cohorts is required.
(Less)
- author
- organization
- publishing date
- 2025-03
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Journal of the National Cancer Institute
- volume
- 117
- issue
- 3
- pages
- 10 pages
- publisher
- Oxford University Press
- external identifiers
-
- pmid:39423142
- scopus:86000721230
- ISSN
- 0027-8874
- DOI
- 10.1093/jnci/djae262
- language
- English
- LU publication?
- yes
- id
- d1796b40-75f5-415f-ab51-846333f806a9
- date added to LUP
- 2025-06-24 10:42:05
- date last changed
- 2025-06-25 03:00:09
@article{d1796b40-75f5-415f-ab51-846333f806a9,
abstract = {{<p>Background: There are currently no molecular tests to identify individual breast cancers where radiotherapy (RT) offers no benefit. Profile for the Omission of Local Adjuvant Radiotherapy (POLAR) is a 16-gene molecular signature developed to identify low-risk cancers where RT will not further reduce recurrence rates. Methods: An individual participant data meta-analysis was performed in 623 patients of node-negative estrogen receptor–positive and HER2-negative early breast cancer enrolled in 3 RT randomized trials for whom primary tumor material was available for analysis. A Cox proportional hazards model on time to locoregional recurrence was used to test the interaction between POLAR score and RT. Results: A total of 429 (69%) patients’ tumors had a high POLAR score, and 194 (31%) had a low score. Patients with high POLAR score had, in the absence of RT, a 10-year cumulative incidence of locoregional recurrence (20%, 95% confidence interval [CI] = 15% to 26%, vs 5%, [CI] 2% to 11%) for those with a low score. Patients with a high POLAR score had a large benefit from RT (hazard ratio [HR] for RT vs no RT = 0.37, 95% CI = 0.23 to 0.60; P < .001). In contrast, there was no evidence of benefit from RT for patients with a low POLAR score (HR = 0.92, 95% CI = 0.42 to 2.02; P = .832). The test for interaction between RT and POLAR was statistically significant (P = .022). Conclusions: POLAR is not only prognostic for locoregional recurrence but also predictive of benefit from RT in selected patients. Patients aged 50 years and older with estrogen receptor–positive and HER2-negative disease and a low POLAR score could consider omitting adjuvant RT. Further validation in contemporary clinical cohorts is required.</p>}},
author = {{Karlsson, Per and Fyles, Anthony and Chang, S. Laura and Arrick, Bradley and Baehner, Frederick L. and Malmström, Per and Fernö, Mårtin and Holmberg, Erik and Sjöström, Martin and Liu, Fei Fei and Cameron, David A. and Williams, Linda J. and Bartlett, John M.S. and Dunlop, Joanna and Caldwell, Jacqueline and Loane, Joseph F. and Mallon, Elizabeth and Piper, Tammy and Kunkler, Ian and Feng, Felix Y. and Speers, Corey W. and Pierce, Lori J. and Bennett, John P. and Taylor, Karen J.}},
issn = {{0027-8874}},
language = {{eng}},
number = {{3}},
pages = {{486--495}},
publisher = {{Oxford University Press}},
series = {{Journal of the National Cancer Institute}},
title = {{Validation of a breast cancer assay for radiotherapy omission : an individual participant data meta-analysis}},
url = {{http://dx.doi.org/10.1093/jnci/djae262}},
doi = {{10.1093/jnci/djae262}},
volume = {{117}},
year = {{2025}},
}