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. 2018 Jul 27;20(1):79.
doi: 10.1186/s13058-018-1012-0.

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

Maj-Britt Jensen  1 , Anne-Vibeke Lænkholm  2 , Torsten O Nielsen  3 , Jens Ole Eriksen  2 , Pernille Wehn  2 , Tressa Hood  4 , Namratha Ram  4 , Wesley Buckingham  4 , Sean Ferree  4 , Bent Ejlertsen  5
Affiliations

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

Maj-Britt Jensen et al. Breast Cancer Res. .

Abstract

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.

Keywords: Adjuvant chemotherapy; Breast neoplasms; CMF; Cyclophosphamide; PAM50.

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Conflict of interest statement

Ethics approval and consent to participate

The Biomedical Research Ethics Committee of the Danish Capital Region approved the protocol (H-15012740), and granted dispensation from consent.

Consent for publication

Not applicable.

Competing interests

MBJ: None. AVL: Nanostring Technologies, Inc.: grant, Roche: grant. TON: Nanostring Technologies, Inc.: personal fees, non-financial support, other: licensing agreement, patent. JOE: none. PW: none. TH: Nanostring Technologies, Inc.: personal fees, other: employee and stock. NR: Nanostring Technologies, Inc.: personal fees: employee. WB: Nanostring Technologies, Inc.: personal fees: employee. SF: Nanostring Technologies, Inc.: other: employee and stock, patent. BE: Nanostring Technologies, Inc:.grant: institutional. Novartis: grant: institutional. Roche: Grant: institutional.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
a Disease-free survival by continuous risk of recurrence (ROR) score 0–5 years and 5–10 years after randomization, respectively, for patients in the systemically untreated regimen (CT –) and patients in the C/CMF arm (CT +). b Overall survival by continuous ROR score for 0–5 years and 5+ years after randomization, respectively. Hazard ratios and corresponding 95% CI for a 10-point difference in continuous ROR score are shown
Fig. 2
Fig. 2
a Kaplan-Meier estimates of disease-free survival in the 113 patients systemically untreated (– CT), according to low, intermediate, and high Prosigna risk of recurrence (ROR) scores. b Kaplan-Meier estimates of overall survival
Fig. 3
Fig. 3
Forest plots illustrate proportional hazard models for disease-free survival (a) and overall survival (b) overall and according to intrinsic cancer subtype and risk of recurrence (ROR) score, respectively. Hazard ratios refer to adjusted estimates obtained in the multivariate analysis. P values are for test of heterogeneity of treatment effect. Boxes represent the weight of data for each subgroup relative to the total data. Pt.s, patients; Lum, luminal; HER2E, human epidermal growth factor receptor 2-enriched
Fig. 4
Fig. 4
Kaplan-Meier estimates of disease-free survival in patients with luminal (Lum) A (a), luminal B (b), basal-like (c), and human epidermal growth factor receptor 2-enriched (HER2-E) (d) breast cancer in the systemically untreated arm (–CT) and in the cyclophosphamide/cyclophosphamide, methotrexate and fluorouracil arm (+CT)
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References

    1. Bonadonna G, Brusamolino E, Valagussa P, Rossi A, Brugnatelli L, Brambilla C, et al. Combination chemotherapy as an adjuvant treatment in operable breast cancer. N Engl J Med. 1976;294:405–410. doi: 10.1056/NEJM197602192940801. - DOI - PubMed
    1. Ejlertsen B, Mouridsen HT, Jensen MB, Andersen J, Andersson M, Kamby C, et al. Cyclophosphamide, methotrexate, and fluorouracil; oral cyclophosphamide; levamisole; or no adjuvant therapy for patients with high-risk, premenopausal breast cancer. Cancer. 2010;116(9):2081–2089. - PubMed
    1. Anonymous Adjuvant chemotherapy of breast cancer. NIH consensus development conference, July 14–16, 1980. Cancer Treat Res. 1992;60:371–374. - PubMed
    1. Early Breast Cancer Trialists’ Collaborative Group (EBCTCG) Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials. Lancet. 2005;365:1687–1717. doi: 10.1016/S0140-6736(05)66544-0. - DOI - PubMed
    1. Peto R, Davies C, Godwin J, Gray R, Pan HC, Clarke M, et al. Comparisons between different polychemotherapy regimens for early breast cancer: meta-analyses of long-term outcome among 100,000 women in 123 randomised trials. Lancet. 2012;379:432–444. doi: 10.1016/S0140-6736(11)61625-5. - DOI - PMC - PubMed

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