The Prosigna gene expression assay and responsiveness to adjuvant cyclophosphamide-based chemotherapy in premenopausal high-risk patients with breast cancer
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The Prosigna gene expression assay and responsiveness to adjuvant cyclophosphamide-based chemotherapy in premenopausal high-risk patients with breast cancer. / Jensen, Maj-Britt; Lænkholm, Anne-Vibeke; Nielsen, Torsten O; Eriksen, Jens Ole; Wehn, Pernille; Hood, Tressa; Ram, Namratha; Buckingham, Wesley; Ferree, Sean; Ejlertsen, Bent.
I: Breast cancer research : BCR, Bind 20, 79, 2018.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - The Prosigna gene expression assay and responsiveness to adjuvant cyclophosphamide-based chemotherapy in premenopausal high-risk patients with breast cancer
AU - Jensen, Maj-Britt
AU - Lænkholm, Anne-Vibeke
AU - Nielsen, Torsten O
AU - Eriksen, Jens Ole
AU - Wehn, Pernille
AU - Hood, Tressa
AU - Ram, Namratha
AU - Buckingham, Wesley
AU - Ferree, Sean
AU - Ejlertsen, Bent
PY - 2018
Y1 - 2018
N2 - 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 (Pinteraction = 0.003 unadjusted, P = 0.001 adjusted) and OS (Pinteraction = 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.
AB - 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 (Pinteraction = 0.003 unadjusted, P = 0.001 adjusted) and OS (Pinteraction = 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.
KW - Adult
KW - Antineoplastic Combined Chemotherapy Protocols/therapeutic use
KW - Breast/pathology
KW - Breast Neoplasms/genetics
KW - Chemotherapy, Adjuvant/methods
KW - Clinical Trials, Phase III as Topic
KW - Cyclophosphamide/therapeutic use
KW - Disease-Free Survival
KW - Female
KW - Fluorouracil/therapeutic use
KW - Follow-Up Studies
KW - Gene Expression Profiling/methods
KW - Humans
KW - Mastectomy
KW - Methotrexate/therapeutic use
KW - Middle Aged
KW - Neoplasm Recurrence, Local/diagnosis
KW - Predictive Value of Tests
KW - Premenopause
KW - Prognosis
KW - Receptor, ErbB-2/metabolism
KW - Retrospective Studies
KW - Risk Assessment/methods
U2 - 10.1186/s13058-018-1012-0
DO - 10.1186/s13058-018-1012-0
M3 - Journal article
C2 - 30053900
VL - 20
JO - Breast Cancer Research
JF - Breast Cancer Research
SN - 1465-5411
M1 - 79
ER -
ID: 222330615