The Prosigna gene expression assay and responsiveness to adjuvant cyclophosphamide-based chemotherapy in premenopausal high-risk patients with breast cancer

Maj Britt Jensen*, Anne Vibeke Lænkholm, Torsten O. Nielsen, Jens Ole Eriksen, Pernille Wehn, Tressa Hood, Namratha Ram, Wesley Buckingham, Sean Ferree, Bent Ejlertsen

*Corresponding author for this work

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Background: The PAM50-based (Prosigna) risk of recurrence (ROR) score and intrinsic subtypes are prognostic for women with high-risk breast cancer. We investigate the predictive ability of Prosigna regarding the effectiveness of cyclophosphamide-based adjuvant chemotherapy in premenopausal patients with high-risk breast cancer. Methods: Prosigna assays were performed on the NanoString platform in tumors from participants in Danish Breast Cancer Group (DBCG) 77B, a four-arm trial that randomized premenopausal women with high-risk early breast cancer to no systemic treatment, levamisole, oral cyclophosphamide (C) or cyclophosphamide, methotrexate and fluorouracil (CMF). Results: In total, this retrospective analysis included 460 women (40% of the 1146 randomized patients). The continuous Prosigna ROR score was prognostic in the no systemic treatment group (unadjusted P<0.001 for disease-free survival (DFS), P=0.001 for overall survival (OS)). No statistically significant interaction of continuous ROR score and treatment on DFS and OS was found. A highly significant association was observed between intrinsic subtypes and C/CMF treatment for DFS (P interaction=0.003 unadjusted, P=0.001 adjusted) and OS (P interaction=0.04). In the adjusted analysis treatment with C/CMF was associated with a reduced risk of DFS events in patients with basal-like (hazard ratio (HR) 0.14; 95% CI 0.06; 0.32) and luminal B (HR 0.48; 95% CI 0.27; 0.84) subtypes but not in patients with Human epidermal growth factor receptor-enriched (HR 1.05; 95% CI 0.56; 1.95) or luminal A (HR 0.61; 95% CI 0.32; 1.16) subtypes. Conclusion: The Prosigna ROR score and intrinsic subtypes were prognostic in high-risk premenopausal patients with breast cancer, and intrinsic subtypes identify high-risk patients with or without major benefit from adjuvant C/CMF treatment.

Original languageEnglish
Article number79
JournalBreast Cancer Research
Issue number1
Number of pages10
Publication statusPublished - 27. Jul 2018


  • Adjuvant chemotherapy
  • Breast neoplasms
  • CMF
  • Cyclophosphamide
  • PAM50
  • Breast/pathology
  • Cyclophosphamide/therapeutic use
  • Predictive Value of Tests
  • Prognosis
  • Follow-Up Studies
  • Humans
  • Middle Aged
  • Fluorouracil/therapeutic use
  • Clinical Trials, Phase III as Topic
  • Mastectomy
  • Adult
  • Female
  • Retrospective Studies
  • Risk Assessment/methods
  • Neoplasm Recurrence, Local/diagnosis
  • Methotrexate/therapeutic use
  • Receptor, ErbB-2/metabolism
  • Gene Expression Profiling/methods
  • Premenopause
  • Chemotherapy, Adjuvant/methods
  • Antineoplastic Combined Chemotherapy Protocols/therapeutic use
  • Disease-Free Survival
  • Breast Neoplasms/genetics


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