Abstract

Abstract Purpose We have identified 34 genes of interest that can distinguish post-mastectomy cancer patients into high- and low-risk of locoregional recurrence (LRR) in 2006. In this study, we validate the performance of 18 of 34 genes in prediction of LRR after mastectomy and breast conserving surgery (BCS). Materials and methods A total of 124 breast cancer patients who underwent mastectomy from 2005 to 2012 and had DNA microarray study on the primary tumor tissues were chosen for this study. Eligible patients should have no post-mastectomy radiotherapy (PMRT) with a minimum of 2-year follow-up. Among the 34 genes in previous report, only 30 genes could be found in Affymetrix U95 to U133 Plus2.0 array. Eighteen of 30 genes (18-Gene classifier) were used to distinguish low-risk and high-risk patients. Patients with 18-Gene score 31 or more were defined as high-risk and score less than 31 defined as low-risk group. We then examined the performance of the 18-Gene classifier in breast conserving patients (n=87) who usually had adjuvant radiotherapy (94%) and were treated in the same study periods. Results The overall accuracy of the prediction of LRR is 87% (sensitivity 91% and specificity 87%). By the 18-Gene classifier, the 5-year LRR rate in high-risk group was 42%, and in low-risk group <1% (p < 0.0001). LRR and 18-gene score in non-PMRT patients18-Gene scoreNo LRR #LRR #5-year LR control probabilityScore <31971100%Score >= 31151157.7% 11212 LRR: Locoregional recurrence Multivariate analysis of mastectomy patients revealed that 18-Gene score is the independent prognostic factor that predicts the likelihood of LRR regardless of nodal status and breast cancer subtype. The predictive ability of LRR by the 18-Gene classifier in BCS patients is independent from adjuvant radiotherapy, and is consistent with the performance in mastectomy patients. Multivariate analysis in BCS patientsRisk factorPatient #LRR #LRR rateUnivariate analysisMultivariate analysisLVI Absent/focal7345.5% Prominent14321.4%4.3(1.0,19.3)5.1*(1.1,23.1)18-Gene score Low risk6623.0% High risk21523.8%9.4*(1.8,48.4)10.4*(2.0,54.2)Adjuvant R/T No5240%10.3*(2.0,53.9) Yes8256.1% LVI: lymphovascular invasion; R/T: radiotherapy; *p<0.05 Discussion This 18-Gene classifier is capable of identifying high-risk patients of LRR after mastectomy and breast conserving surgery. Citation Format: Cheng H-CS, Horng C-F, Huang T-T, Tsou M-H, Shih L-S, Yu B-L, Tsai Y-C, Chen C-M. Validation of gene expression profiling in prediction of locoregional recurrence for breast cancer patients after surgery. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P2-08-14.

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