An Eighteen-Gene Classifier Predicts Locoregional Recurrence in Post-Mastectomy Breast Cancer Patients

Skye H Cheng, Chen-Fang Horng, Tzu-Ting Huang, Erich S Huang, Mei-Hua Tsou, Li-Sun Shi, Ben-Long Yu, Chii-Ming Chen, Andrew T Huang, Skye H Cheng, Chen-Fang Horng, Tzu-Ting Huang, Erich S Huang, Mei-Hua Tsou, Li-Sun Shi, Ben-Long Yu, Chii-Ming Chen, Andrew T Huang

Abstract

We previously identified 34 genes of interest (GOI) in 2006 to aid the oncologists to determine whether post-mastectomy radiotherapy (PMRT) is indicated for certain patients with breast cancer. At this time, an independent cohort of 135 patients having DNA microarray study available from the primary tumor tissue samples was chosen. Inclusion criteria were 1) mastectomy as the first treatment, 2) pathology stages I-III, 3) any locoregional recurrence (LRR) and 4) no PMRT. After inter-platform data integration of Affymetrix U95 and U133 Plus 2.0 arrays and quantile normalization, in this paper we used 18 of 34 GOI to divide the mastectomy patients into high and low risk groups. The 5-year rate of freedom from LRR in the high-risk group was 30%. In contrast, in the low-risk group it was 99% (p < 0.0001). Multivariate analysis revealed that the 18-gene classifier independently predicts rates of LRR regardless of nodal status or cancer subtype.

Keywords: Breast cancer; Breast-conserving surgery; Gene-expression profiles; Locoregional recurrence; Mastectomy; Prediction; Radiotherapy.

Figures

Fig. 1
Fig. 1
Diagram to develop gene expression profiling that predicts locoregional recurrence in mastectomy patients. The genes of interest (GOI) reduced from 258 to 18 and maintained a similar, or greater ability to partition the low and high risk patients after mastectomy.
Fig. 2
Fig. 2
An unsupervised cluster analysis of 18 genes and supervised clustering in 135 patients according to the 18-gene scores revealed distinct gene expression profiles in patients with and without recurrence. Patients with locoregional recurrence (LRR) are colored as blue (), both LRR and distant metastasis are colored as purple (), distant metastasis patients are colored as red (), and disease free patients are colored as yellow () in the bottom of the heatmap.
Fig. 3
Fig. 3
(a) The receiver operating characteristic (ROC) curve constructed from 18-gene scoring algorithm as a predictor of locoregional recurrence in patients after mastectomy. The area under the receiver ROC curve: 0.752 ± 0.040 (95% CI: 0.672–0.831) (p ) represents disease free; the light green triangle () represents LRR and distant recurrences simultaneously; the red square () represents LRR; and the light blue rhombus () represents distant metastasis.

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