1. The Prosigna 50-gene profile and responsiveness to adjuvant anthracycline-based chemotherapy in high-risk breast cancer patients
- Author
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Jeanette Dupont Jensen, Torsten O. Nielsen, Eva Balslev, Ann Knoop, Wesley Buckingham, Anne-Vibeke Lænkholm, Maj-Britt Jensen, Sean Ferree, Vesna Glavicic, Henning T. Mouridsen, Bent Ejlertsen, and Dorte Nielsen
- Subjects
0301 basic medicine ,Oncology ,medicine.medical_specialty ,Cyclophosphamide ,Anthracycline ,medicine.medical_treatment ,Predictive markers ,lcsh:RC254-282 ,Article ,03 medical and health sciences ,0302 clinical medicine ,Breast cancer ,Internal medicine ,medicine ,Clinical endpoint ,Pharmacology (medical) ,Radiology, Nuclear Medicine and imaging ,Chemotherapy ,business.industry ,Hazard ratio ,medicine.disease ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,030104 developmental biology ,Fluorouracil ,030220 oncology & carcinogenesis ,Randomized controlled trials ,business ,medicine.drug ,Epirubicin - 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.
- Published
- 2020
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