A 23-gene prognostic classifier for prediction of recurrence and survival for Asian breast cancer patients

Abstract

We report a 23- gene-classifier profiled from Asian women, with the primary purpose of assessing its clinical utility towards improved risk stratification for relapse for breast cancer patients from Asian cohorts within 10 years’ following mastectomy. Four hundred and twenty-two breast cancer patients underwent mastectomy and were used to train the classifier on a logistic regression model. A subset of 197 patients were chosen to be entered into the follow-up studies post mastectomy who were examined to determine the patterns of recurrence and survival analysis based on gene expression of the gene classifier, age at diagnosis, tumor stage and lymph node status, over a 5 and 10 years follow-up period. Metastasis to lymph node (N2-N3) with N0 as the reference (N2 vs. N0 hazard ratio: 2.02 (1.05–8.70), N3 vs. N0 hazard ratio: 4.32 (1.41–13.22) for 5 years) and gene expression of the 23-gene panel (P=0.06, 5 years and 0.02, 10 years, log-rank test) were found to have significant discriminatory effects on the risk of relapse (HR (95%CI):2.50 (0.95–6.50)). Furthermore, survival curves for subgroup analysis with N0-N1 and T1-T2 predicted patients with higher risk scores. The study provides robust evidence of the effectiveness of the 23-gene-classifier and could be used to determine the risk of relapse event (locoregional and distant recurrence) in Asian patients, leading to a meaningful reduction in chemotherapy recommendations.

Comparing Genetic Risk and Clinical Risk Classification in Luminal-like Breast Cancer Patients Using a 23-Gene Classifier

“…In addition to the well-known published MGAs, the 23-gene signature has been validated for its discriminating ability in addition to pathological prognostic factors such as tumor size and nodal status [ 9 ]. In one study, the prognostic discrepancy in 5-year relapse-free survival was evidenced between the predicted high- and low-risk groups [ 9 , 14 ]. Chronologically and collectively, the proposed signature has been validated across microarray and RT-PCR platforms [ 9 , 14 ].…”

“…Development of the 23-gene classifier has been described elsewhere [ 9 , 14 ]. This classifier is an MGA, which interrogates functionalities associated with cell cycl and proliferation, oncogenic processes, inflammation and immune response, apoptosis and metabolism.…”

Prognostic Comparison between Oncotype DX® and a 23-Gene Classifier, RecurIndex®, on the Taiwan Breast Cancer Population

“…The development of the 23-gene classifier has been described previously [ 10 , 11 , 12 ]. The primer pairs of the 23-genes were set into the 96-well plates to conduct RT-PCR by using the total RNA isolated from the FFPE tumor tissues.…”

“…In contrast with the non-Hispanic white population, the pattern of breast cancer-specific mortality among Asian node-negative patients is different from that in non-Hispanic white reference populations [ 9 ]. Hence, a 23-gene classifier was developed using gene expression profiles from the breast cancer patients in Taiwan [ 10 , 11 ].…”

“…The 23-gene classifier, RecurIndex ® , was initially developed using the microarray platform technology [ 10 , 11 , 12 ] to evaluate the prognosis capability of the test in classifying Asian breast cancer patients into two categories, high and low risks of distant recurrence (DR). This 23-gene genomic test comprises 20 breast cancer recurrence-related genes with three housekeeping genes and six clinical factors (the age at first diagnosis, the nodal stage, the tumor grading, the tumor size, the estrogen receptor (ER) status, and the lymphovascular invasion (LVI) status) [ 12 ].…”