Prognostic algorithm identified in node-negative early breast cancer patients predicts outcome also in node-positive patients treated with adjuvant chemotherapy

• Published in: Cancer research (Chicago, Ill.) Vol. 69; no. 2_Supplement; p. 6044
• Main Authors: Kronenwett, R, Kalogeras, KT, Stropp, U, Weber, K, Dafni, U, Gehrmann, M, Pectasides, D, von Toerne, C, Papakostas, P, Wirtz, RM, Fountzilas, G
• Format: Journal Article
• Language: English
• Published: 15-01-2009
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/0008-5472.SABCS-6044

Abstract
Abstract #6044
Background: Recently, we identified and validated a prognostic multigene score, which predicted outcome in early node-negative breast cancer patients that did not receive systemic therapy. The aim of this study was to examine the performance of our prognostic multigene algorithm in node-positive patients treated with adjuvant chemotherapy.
 Patients and Methods: Patients were treated with adjuvant anthracycline-based chemotherapy in the context of a randomized Phase III study. This was a two-arm trial (E-CMF vs. E-T-CMF) investigating postoperative dose-dense sequential chemotherapy with epirubicin (E) followed by CMF with or without paclitaxel (T). RNA was isolated from 222 formalin-fixed, paraffin-embedded tumor tissue samples, using a Siemens proprietary automated method based on silica-coated magnetic beads, followed by kinetic one-step RT-PCR for mRNA expression analysis of 9 informative genes and 2 normalization genes. For each patient a risk score was calculated using a linear combination of expression values. Patients were separated into high, intermediate and low risk by applying two thresholds of the score. As used in node-negative patients, distant metastasis-free survival (MFS) and overall survival (OS) were estimated by the Kaplan-Meier method and compared using the log-rank test. Cox analysis for MFS and OS was also performed.
 Results: The prognostic score could be calculated for 213 patients (102 E-T-CMF; 111 E-CMF). Looking at all patients independently of type of chemotherapy, the score could classify the patients into three distinct risk groups, which were significantly different in terms of MFS (log-rank test, p=0.004) and OS (p=0.01). The separation of the risk groups was even better when focusing on patients with more than three involved lymph nodes (MFS: p=0.0001; OS: p=0.0015; n=166). The respective analysis of the two treatment arms showed that the separation of the risk groups was only significant in E-CMF-treated patients (E-CMF: p=0.002; E-T-CMF: p=0.37). Interestingly, the subgroup of patients with more than three involved lymph nodes and classified as intermediate or high risk (n=77) had a nearly significant better MFS when treated with E-T-CMF in comparison with E-CMF (p=0.07; HR: 0.53; 95% CI: 0.2685 to 1.060).
 Conclusions: Our prognostic algorithm, identified and validated in node-negative patients that had not been systemically treated, predicts outcome also in node-positive chemotherapy-treated patients. Our findings suggest that the prognostic score may also be predictive of benefit from the addition of taxanes to adjuvant chemotherapy. This hypothesis needs to be confirmed in a larger cohort of samples from an independent clinical study.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 6044.