Prosigna Risk of Recurrence score and intrinsic subtypes are associated with adjuvant anthracycline chemotherapy benefit in high-risk breast cancer

Abstract NCIC-CTG MA.5 and DBCG 89D are symmetrically designed randomized trials comparing adjuvant cyclophosphamide, epirubicin, and fluorouracil with cyclophosphamide, methotrexate, and fluorouracil in high-risk breast cancer patients. In a joint analysis we evaluate the predictive value in terms...

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Main Authors: Maj-Britt Jensen, Torsten O. Nielsen, John Bartlett, Anne-Vibeke Lænkholm, Lois Shepherd, Bent Ejlertsen
Format: Article
Language:English
Published: Nature Portfolio 2025-03-01
Series:npj Breast Cancer
Online Access:https://doi.org/10.1038/s41523-025-00738-7
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author Maj-Britt Jensen
Torsten O. Nielsen
John Bartlett
Anne-Vibeke Lænkholm
Lois Shepherd
Bent Ejlertsen
author_facet Maj-Britt Jensen
Torsten O. Nielsen
John Bartlett
Anne-Vibeke Lænkholm
Lois Shepherd
Bent Ejlertsen
author_sort Maj-Britt Jensen
collection DOAJ
description Abstract NCIC-CTG MA.5 and DBCG 89D are symmetrically designed randomized trials comparing adjuvant cyclophosphamide, epirubicin, and fluorouracil with cyclophosphamide, methotrexate, and fluorouracil in high-risk breast cancer patients. In a joint analysis we evaluate the predictive value in terms of anthracycline benefit of molecular subtyping by PAM50. A statistically significant interaction (P = 0.008) between continuous Risk of Recurrence (ROR) score and treatment regimen is evident, translating into a clear distinct treatment effect according to ROR score category with HR 0.51 for ROR score ≥ 72 and HR 1.10 for ROR score < 52 (Pinteraction = 0.004). The analysis provides evidence of the benefit from anthracycline in HER2-enriched subtype; for patients with discordance of HER2 subtype and clinical HER2 status, HER2-enriched subtype was predictive of anthracycline benefit whereas clinical HER2 positive status was not. Anthracycline-based adjuvant chemotherapy may safely be withheld for patients with a low ROR score while the benefit increases with increasing ROR score.
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issn 2374-4677
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publishDate 2025-03-01
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series npj Breast Cancer
spelling doaj-art-f4f5c80a7e5348e59c5891085a796ff52025-08-20T02:56:15ZengNature Portfolionpj Breast Cancer2374-46772025-03-011111710.1038/s41523-025-00738-7Prosigna Risk of Recurrence score and intrinsic subtypes are associated with adjuvant anthracycline chemotherapy benefit in high-risk breast cancerMaj-Britt Jensen0Torsten O. Nielsen1John Bartlett2Anne-Vibeke Lænkholm3Lois Shepherd4Bent Ejlertsen5Danish Breast Cancer Cooperative Group, Department of Oncology, Copenhagen University HospitalDepartment of Pathology and Laboratory Medicine, Genetic Pathology Evaluation Centre, University of British ColumbiaCancer Research UK Scotland Centre, University of EdinburghDepartment of Surgical Pathology, Zealand University HospitalCanadian Cancer Trials Group, Queen’s UniversityDanish Breast Cancer Cooperative Group, Department of Oncology, Copenhagen University HospitalAbstract NCIC-CTG MA.5 and DBCG 89D are symmetrically designed randomized trials comparing adjuvant cyclophosphamide, epirubicin, and fluorouracil with cyclophosphamide, methotrexate, and fluorouracil in high-risk breast cancer patients. In a joint analysis we evaluate the predictive value in terms of anthracycline benefit of molecular subtyping by PAM50. A statistically significant interaction (P = 0.008) between continuous Risk of Recurrence (ROR) score and treatment regimen is evident, translating into a clear distinct treatment effect according to ROR score category with HR 0.51 for ROR score ≥ 72 and HR 1.10 for ROR score < 52 (Pinteraction = 0.004). The analysis provides evidence of the benefit from anthracycline in HER2-enriched subtype; for patients with discordance of HER2 subtype and clinical HER2 status, HER2-enriched subtype was predictive of anthracycline benefit whereas clinical HER2 positive status was not. Anthracycline-based adjuvant chemotherapy may safely be withheld for patients with a low ROR score while the benefit increases with increasing ROR score.https://doi.org/10.1038/s41523-025-00738-7
spellingShingle Maj-Britt Jensen
Torsten O. Nielsen
John Bartlett
Anne-Vibeke Lænkholm
Lois Shepherd
Bent Ejlertsen
Prosigna Risk of Recurrence score and intrinsic subtypes are associated with adjuvant anthracycline chemotherapy benefit in high-risk breast cancer
npj Breast Cancer
title Prosigna Risk of Recurrence score and intrinsic subtypes are associated with adjuvant anthracycline chemotherapy benefit in high-risk breast cancer
title_full Prosigna Risk of Recurrence score and intrinsic subtypes are associated with adjuvant anthracycline chemotherapy benefit in high-risk breast cancer
title_fullStr Prosigna Risk of Recurrence score and intrinsic subtypes are associated with adjuvant anthracycline chemotherapy benefit in high-risk breast cancer
title_full_unstemmed Prosigna Risk of Recurrence score and intrinsic subtypes are associated with adjuvant anthracycline chemotherapy benefit in high-risk breast cancer
title_short Prosigna Risk of Recurrence score and intrinsic subtypes are associated with adjuvant anthracycline chemotherapy benefit in high-risk breast cancer
title_sort prosigna risk of recurrence score and intrinsic subtypes are associated with adjuvant anthracycline chemotherapy benefit in high risk breast cancer
url https://doi.org/10.1038/s41523-025-00738-7
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