EndoPredict improves the prognostic classification derived from common clinical guidelines in ER-positive, HER2-negative early breast cancer

P Dubsky, M Filipits, R Jakesz, M Rudas, C F Singer, R Greil, O Dietze, I Luisser, E Klug, R Sedivy, M Bachner, D Mayr, M Schmidt, M C Gehrmann, C Petry, K E Weber, R Kronenwett, J C Brase, M Gnant, Austrian Breast and Colorectal Cancer Study Group (ABCSG), P Dubsky, M Filipits, R Jakesz, M Rudas, C F Singer, R Greil, O Dietze, I Luisser, E Klug, R Sedivy, M Bachner, D Mayr, M Schmidt, M C Gehrmann, C Petry, K E Weber, R Kronenwett, J C Brase, M Gnant, Austrian Breast and Colorectal Cancer Study Group (ABCSG)

Abstract

Background: In early estrogen receptor (ER)-positive/HER2-negative breast cancer, the decision to administer chemotherapy is largely based on prognostic criteria. The combined molecular/clinical EndoPredict test (EPclin) has been validated to accurately assess prognosis in this population. In this study, the clinical relevance of EPclin in relation to well-established clinical guidelines is assessed.

Patients and methods: We assigned risk groups to 1702 ER-positive/HER2-negative postmenopausal women from two large phase III trials treated only with endocrine therapy. Prognosis was assigned according to National Comprehensive Cancer Center Network-, German S3-, St Gallen guidelines and the EPclin. Prognostic groups were compared using the Kaplan-Meier survival analysis.

Results: After 10 years, absolute risk reductions (ARR) between the high- and low-risk groups ranged from 6.9% to 11.2% if assigned according to guidelines. It was at 18.7% for EPclin. EPclin reassigned 58%-61% of women classified as high-/intermediate-risk (according to clinical guidelines) to low risk. Women reclassified to low risk showed a 5% rate of distant metastasis at 10 years.

Conclusion: The EPclin score is able to predict favorable prognosis in a majority of patients that clinical guidelines would assign to intermediate or high risk. EPclin may reduce the indications for chemotherapy in ER-positive postmenopausal women with a limited number of clinical risk factors.

Figures

Figure 1
Figure 1
Kaplan–Meier plot of distant metastasis-free survival (MFS) by (A) German S3, (B) National Comprehensive Cancer Center Network (NCCN), (C) St Gallen guidelines and (D) EPclin risk groups. 95% confidence intervals (CI) of hazard ratios (HR) are indicated.
Figure 2
Figure 2
Kaplan–Meier plot of distant metastasis-free survival (MFS) by EPclin risk groups after considering the (A) German S3, (B) National Comprehensive Cancer Center Network (NCCN) and (C) St Gallen guidelines.
Figure 3
Figure 3
Kaplan–Meier plot of distant metastasis-free survival (MFS) by EPclin risk groups after considering the biological subtypes (A) ‘Luminal B’ and (B) ‘Luminal A’.
Figure 4
Figure 4
Kaplan–Meier plot of distant metastasis-free survival (MFS) by EPclin risk groups in (A) grade 1 tumors, (B) grade 2 tumors and (C) grade 3 tumors.
Figure 5
Figure 5
Putative risk classification scheme for estrogen receptor (ER)-positive, HER2-negative breast cancer patients by combining clinical guidelines and the EPclin test. Metastasis-free survival (MFS) rates are based on the 1702 ER-positive, HER2-negative breast cancer samples.

References

    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.
    1. Berry DA, Cronin KA, Plevritis SK, et al. Effect of screening and adjuvant therapy on mortality from breast cancer. N Engl J Med. 2005;353:1784–1792.
    1. Fisher B, Jeong JH, Bryant J, et al. Treatment of lymph-node-negative, oestrogen-receptor-positive breast cancer: long-term findings from National Surgical Adjuvant Breast and Bowel Project randomised clinical trials. Lancet. 2004;364:858–868.
    1. Carlson RW, Brown E, Burstein HJ, et al. NCCN task force report: adjuvant therapy for breast cancer. J Natl Compr Cancer Netw. 2006;4(Suppl 1):S1–S26.
    1. Goldhirsch A, Wood WC, Coates AS, et al. Strategies for subtypes––dealing with the diversity of breast cancer: highlights of the St Gallen international expert consensus on the primary therapy of early breast cancer 2011. Ann Oncol. 2011;22:1736–1747.
    1. Gnant M, Steger GG. Fighting overtreatment in adjuvant breast cancer therapy. Lancet. 2009;374:2029–2030.
    1. Goldhirsch A, Ingle JN, Gelber RD, et al. Thresholds for therapies: highlights of the St Gallen international expert consensus on the primary therapy of early breast cancer 2009. Ann Oncol. 2009;20:1319–1329.
    1. Furness PN, Taub N, Assmann KJ, et al. International variation in histologic grading is large, and persistent feedback does not improve reproducibility. Am J Surg Pathol. 2003;27:805–810.
    1. Sotiriou C, Pusztai L. Gene-expression signatures in breast cancer. N Engl J Med. 2009;360:790–800.
    1. van de Vijver MJ, He YD, van't Veer LJ, et al. A gene-expression signature as a predictor of survival in breast cancer. N Engl J Med. 2002;347:1999–2009.
    1. Wang Y, Klijn JG, Zhang Y, et al. Gene-expression profiles to predict distant metastasis of lymph-node-negative primary breast cancer. Lancet. 2005;365:671–679.
    1. Paik S, Shak S, Tang G, et al. A multigene assay to predict recurrence of tamoxifen-treated, node-negative breast cancer. N Engl J Med. 2004;351:2817–2826.
    1. Filipits M, Rudas M, Jakesz R, et al. A new molecular predictor of distant recurrence in ER-positive, HER2-negative breast cancer adds independent information to conventional clinical risk factors. Clin Cancer Res. 2011;17:6012–6020.
    1. Denkert C, Kronenwett R, Schlake W, et al. Decentral gene expression analysis for ER+/Her2- breast cancer–– results of a proficiency testing program for the EndoPredict assay. Virchows Arch. 2012;460:251–259.
    1. Schmid M, Jakesz R, Samonigg H, et al. Randomized trial of tamoxifen versus tamoxifen plus aminoglutethimide as adjuvant treatment in postmenopausal breast cancer patients with hormone receptor-positive disease: Austrian breast and colorectal cancer study group trial 6. J Clin Oncol. 2003;21:984–990.
    1. Jakesz R, Jonat W, Gnant M, et al. Switching of postmenopausal women with endocrine-responsive early breast cancer to anastrozole after 2 years’ adjuvant tamoxifen: combined results of ABCSG trial 8 and ARNO 95 trial. Lancet. 2005;366:455–462.
    1. Dubsky PC, Jakesz R, Mlineritsch B, et al. Tamoxifen and anastrozole as a sequencing strategy: a randomized controlled trial in postmenopausal patients with endocrine-responsive early breast cancer from the Austrian breast and colorectal cancer study group. J Clin Oncol. 2012;30:722–728. [Epub 2012 Jan 23]
    1. Partin JF, Mamounas EP. Impact of the 21-gene recurrence score assay compared with standard clinicopathologic guidelines in adjuvant therapy selection for node-negative, estrogen receptor-positive breast cancer. Ann Surg Oncol. 2011;18:3399–3406.
    1. Cheang MC, Chia SK, Voduc D, et al. Ki67 index, HER2 status, and prognosis of patients with luminal B breast cancer. J Natl Cancer Inst. 2009;101:736–750.
    1. Bevilacqua P, Verderio P, Barbareschi M, et al. Lack of prognostic significance of the monoclonal antibody Ki-S1, a novel marker of proliferative activity, in node-negative breast carcinoma. Breast Cancer Res Treat. 1996;37:123–133.
    1. Clahsen PC, van de Velde CJ, Duval C, et al. The utility of mitotic index, oestrogen receptor and Ki-67 measurements in the creation of novel prognostic indices for node-negative breast cancer. Eur J Surg Oncol. 1999;25:356–363.
    1. Parker JS, Mullins M, Cheang MC, et al. Supervised risk predictor of breast cancer based on intrinsic subtypes. J Clin Oncol. 2009;27:1160–1167.
    1. Nielsen TO, Parker JS, Leung S, et al. A comparison of PAM50 intrinsic subtyping with immunohistochemistry and clinical prognostic factors in tamoxifen-treated estrogen receptor-positive breast cancer. Clin Cancer Res. 2010;16:5222–5232.
    1. Kan Z, Jaiswal BS, Stinson J, et al. Diverse somatic mutation patterns and pathway alterations in human cancers. Nature. 2010;466:869–873.

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