Gene Expression Profiling for Breast Cancer Prognosis in Chinese Populations

Abstract

To investigate a quantitative reverse transcription polymerase chain reaction (QRT-PCR) assay different from 21-gene assay which can be used to prognosticate the risk of recurrence in patients with estrogen receptor (ER) positive, lymph node (LN) negative breast cancer. To accurately determine the relationship between the Recurrence Score (RS) derived from our assay and the risk of distant recurrence in Chinese patients with LN negative and positive breast cancer through the analysis of paraffin tissues. We obtained archival paraffin-embedded tissues from patients with invasive breast cancer and varying axillary lymph node involvement. QRT-PCR reaction was performed by using the method of SYBR Green I dye with primers. Expression of the 21-genes was converted to RS by a prespecified algorithm. We then assessed the probability of the test to accurately predict distant recurrence-free survival in this retrospective cohort. Ninety-three patients were eligible based on gene expression profiles. In our population, most breast cancer patients were premenopausal (82.6%), at early stage (93.6%) and ER positive (91.4%). Median follow-up was 65.9 months. The 5-year recurrence-free survival rate for the group was 58.8%. The concordance between the reverse transcription-PCR and immunohistochemical (IHC) measurement for ER, progesterone receptor (PgR), and HER-2 determinations was high and comparable. High RS was predictive of an elevated risk of relapse (p < 0.001). In subgroups of patients, RS had significantly predictive performance both in node-negative (p = 0.009) and node-positive patients (p = 0.038). Multivariable analysis showed that nodal status, adjuvant hormonal therapy and RS were significantly related to prognosis. RS category is a better predictor than the other risk assessment criteria or clinicopatholic features, with which we can determine more accurately the risks for recurrence of various patients. We have established an easy and economical QRT-PCR assay and validated in concordance with IHC measurements for ER, PgR, and HER-2. RS was associated with distant recurrence among Chinese patients with hormone receptor (HR) positive breast cancer. This study may promote the use of RS estimated from the expression of the 21-gene set for prognostication and routine clinical diagnostic application in Chinese populations.