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The Prosigna 50-gene profile and responsiveness to adjuvant anthracycline-based chemotherapy in high-risk breast cancer patients

Authors
  • Jensen, Maj-Britt1
  • Lænkholm, Anne-Vibeke2
  • Balslev, Eva3
  • Buckingham, Wesley4
  • Ferree, Sean4
  • Glavicic, Vesna5
  • Dupont Jensen, Jeanette6
  • Søegaard Knoop, Ann7
  • Mouridsen, Henning T.1
  • Nielsen, Dorte8
  • Nielsen, Torsten O.9
  • Ejlertsen, Bent10
  • 1 Danish Breast Cancer Cooperative Group, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark , Copenhagen (Denmark)
  • 2 Department of Surgical Pathology, Zealand University Hospital, Slagelse, Denmark , Slagelse (Denmark)
  • 3 Department of Pathology, Herlev and Gentofte Hospital, University of Copenhagen, Herlev, Denmark , Herlev (Denmark)
  • 4 NanoString Technologies Inc, Seattle, WA, USA , Seattle (United States)
  • 5 Department of Oncology, Zealand University Hospital, Naestved, Denmark , Naestved (Denmark)
  • 6 Department of Oncology, Odense University Hospital, Odense, Denmark , Odense (Denmark)
  • 7 Department of Oncology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark , Copenhagen (Denmark)
  • 8 Department of Oncology, Herlev and Gentofte Hospital, University of Copenhagen, Herlev, Denmark , Herlev (Denmark)
  • 9 Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada , Vancouver (Canada)
  • 10 Danish Breast Cancer Cooperative Group, Department of Oncology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark , Copenhagen (Denmark)
Type
Published Article
Journal
npj Breast Cancer
Publisher
Nature Publishing Group UK
Publication Date
Feb 26, 2020
Volume
6
Issue
1
Identifiers
DOI: 10.1038/s41523-020-0148-0
Source
Springer Nature
License
Green

Abstract

The DBCG89D trial randomized high-risk early breast cancer patients to adjuvant CMF (cyclophosphamide, methotrexate and fluorouracil) or CEF (cyclophosphamide, epirubicin and fluorouracil). Prosigna assays were performed by researchers with no access to clinical data. Time to distant recurrence (DR) was the primary endpoint, time to recurrence (TR) and overall survival (OS) secondary. Among the 980 Danish patients enrolled, Prosigna results were obtained in 686. Continuous ROR score was associated with DR for CMF (adjusted hazard ratio (HR) 1.20, 95% CI 1.09–1.33), and for CEF (HR 1.04, 95% CI 0.92–1.18), Pinteraction = 0.06. DR was significantly longer in CEF compared to CMF treated patients with Her2-enriched tumors (HR 0.58, 95% CI 0.38–0.86), but not in patients with luminal tumors. Heterogeneity of treatment effect was significant for TR and OS. In this prospective-retrospective analysis, patients with Her2-enriched breast cancer derived substantial benefit from anthracycline chemotherapy whereas anthracyclines are not an essential component of chemotherapy for patients with luminal subtypes. The benefit of CEF vs. CMF correlated with increasing ROR Score.

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