Gene expression profiling in prognosis of distant recurrence in HR-positive and HER2-negative breast cancer patients

Tzu-Ting Huang, Nicolas Pennarun, Yu-Hao Cheng, Cheng-Fang Horng, Jason Lei, Skye Hung-Chun Cheng, Tzu-Ting Huang, Nicolas Pennarun, Yu-Hao Cheng, Cheng-Fang Horng, Jason Lei, Skye Hung-Chun Cheng

Abstract

There had been several studies using gene-expression profiling in predicting distant recurrence in breast cancer. In this study, we developed an 18-gene classifier (18-GC) to predict distant recurrence of breast cancer and compared it with the 21-gene panel (Oncotype DX®, ODx) in performance. Included were 224 breast cancer patients with positive hormonal receptor (HR+) and negative human epidermal growth factor receptor 2 (HER2-). We compared the demographic, clinical, and survival information of the patients, and further compared the prediction of recurrence risk obtained by using the 18-GC with that by ODx. To have the best combined sensitivity and specificity, receiver operating characteristics (ROC) curve analysis was performed to determine the cutoff values for several breakpoint scores. For the new 18-GC, a breakpoint score of 21 was adopted to produce a combined highest sensitivity (95%) and specificity (39%) in detecting distant recurrence. At this breakpoint score, 164 of the 224 patients were classified by the 18-GC in the same risk level as by ODx, giving a concordance rate of 73%. Along with patient age and tumor stage, this 18-GC was found to be an independent significant prognostic factor of distant metastasis of breast cancer. We have thus created a new gene panel assay for prediction of distant recurrence in HR+ and HER2- breast cancer patients. With a high concordance rate with ODx, this new assay may serve as a good tool for individual breast cancer patients to make an informed decision on whether adjuvant chemotherapy should be performed post-surgery.

Keywords: breast cancer; chemotherapy; distant recurrence prediction; gene expression profiling; microarray.

Conflict of interest statement

CONFLICTS OF INTEREST The author (SHC) owns a patent relating to the content of this manuscript (Taiwan patent number: 104115832). None of the authors has any conflicts of interests in this research, either financial or non-financial.

Figures

Figure 1. ROC curve analyses of the…
Figure 1. ROC curve analyses of the 18-GC and ODx
Figure 2. Summary of recurrence hazard ratios…
Figure 2. Summary of recurrence hazard ratios for different risk factors in subgroup analyses
Figure 3. Survival plot analysis of low-…
Figure 3. Survival plot analysis of low- and high-risk patients as determined by the 18-gene classifier

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