R3 정수웅 / Prof. 김시영 This article was published on September 28, 2015, at NEJM.org. DOI: /NEJMoa Prospective Validation of a 21-Gene Expression Assay in Breast Cancer J.A. Sparano, R.J. Gray, D.F. Makower, K.I. Pritchard, K.S. Albain, D.F. Hayes, C.E. Geyer, Jr., E.C. Dees, E.A. Perez, J.A. Olson, J.A. Zujewski, T. Lively, S.S. Badve, T.J. Saphner, L.I. Wagner, T.J. Whelan, M.J. Ellis, S. Paik, W.C. Wood, P. Ravdin, M.M. Keane, H.L. Gomez Moreno, P.S. Reddy, T.F. Goggins, I.A. Mayer, A.M. Brufsky, D.L. Toppmeyer, V.G. Kaklamani, J.N. Atkins, J.L. Berenberg, and G.W. Sledge

Background Prognositc factor for the recurrence of breast cancer tumor size, tumor grade, the number of axillary lymph node with metastasis A National Institute of Health consensus panel in 2001 conclude that adjuvant chemotherapy ……. should be recommended to the majority of women with localized breast cancer regardless of lymph node, menopausal, or hormone receptor status. How beneficial are polychemotherapy in a patient with hormone-receptor positive and axillary node-negative breast cancer ?? an absolute benefit in the rate of freedom from recurrence of up to 5 percentage overtreatment with chemotherapy on the basis of clinicopathogic features alone ??

Background Previous studies on 21-gene expression assay additional prognostic information prediction of benefit from adjuvant chemotherapy in estrogen-receptor positive disease Prospective validation was performed with the use of archival tumor specimens from completed studies that used a prospective-retrospective design. Prospectively conducted studies provides the highest level of evidence supporting the clinical validity of a new biomarker. N Engl J Med 2004;351:

Methods – study patient women 18 to 75 years of age axillary node-negative invasive breast cancer ER-positive or PR-positive or both no overexpression of HER2 a 1.1 to 5.0 cm-sized tumor in the greatest dimension for any grade a 0.6 to 1.0 cm-sized tumor in the greatest dimension for intermediate or high histologic grade or nuclear grade EOCG performance status score 0~1 normal hematologic, bone marrow, hepatic, renal, pulmonary, and cardiac function exclusion of HER2-overexpressed tumor because of a high risk of recurrence

Methods – study protocol 10,253 eligible patients were enrolled between April, 2006, and October, 2010 prospective clinical trial sponsored by the National Cancer Institute (NCI) the median follow-up in the low risk cohort was 69 months recurrence-score ranges in this study lower than those that were originally defined. minimize the potential for undertreatment low ≤ 10 vs. ≤18 intermediate 11~25 vs. 18~30 high ≥25 vs. ≥31 Oncotype DX Recurrence score 0~10 11~25 26~100 endocrine therapy alone chemotherapy plus endocrine therapy or endocrine therapy alonechemotherapy plus endocrine therapy

Methods – study end points The standardized definitions for efficacy end points (STEEP) criteria were used for the end point definitions The primary end point a time-to-event analysis of invasive disease-free survival The secondary end point a time-to-event analysis of distant recurrence-free survival a time-to-event analysis of recurrence-free survival a time-to-event analysis of overall survival J Clin Oncol. J Clin Oncol May 20;25(15):

A total of 6 patients received adjuvant chemotherapy. 1 of whom had a recurrence despite adjuvant chemotherapy

88 events either invasive cancer or death within 5 years after study entry local or regional recurrence (or both) – 8 pts distant recurrence – 10 pts invasive cancer of the opposite breast – 15 pts other invasive new primary cancer – 43 pts death without another event – 12 pts 93.8% (95% CI, 92.4~94.9) 99.3% (95% CI, 98.7~99.6) 98.7% (95% CI, 97.9~99.2) 98.0% (95% CI, 97.1~98.6)

Conclusion This prospective study involving uniformly treated patients with hormone receptor–positive, HER2-negative, axillary node–negative breast cancer supports the clinical validity of the 21-gene assay in identifying patients who may be safely spared adjuvant chemotherapy.