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

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 - 2018/7/27

Y1 - 2018/7/27

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 (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.

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 (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.

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

SN - 1465-5411

VL - 20

JO - Breast Cancer Research

JF - Breast Cancer Research

M1 - 79

ER -