BackgroundSeveral prognostic factors affect the recurrence of breast cancer in patients who undergo mastectomy. Assays of the expression profiles of multiple genes increase the probability of overexpression of certain genes and thus can potentially characterize the risk of metastasis.MethodsWe propose a 20-gene classifier for predicting patients with high/low risk of recurrence within 5 years. Gene expression levels from a quantitative PCR assay were used to screen 473 luminal breast cancer patients treated at Taiwan Hospital (positive for estrogen and progesterone receptors, negative for human epidermal growth factor receptor 2). Gene expression scores, along with clinical information (age, tumor stage, and nodal stage), were evaluated for risk prediction. The classifier could correctly predict patients with and without relapse (logistic regression, P<0.05).ResultsA Cox proportional hazards regression analysis showed that the 20-gene panel was prognostic with hazard ratios of 5.63 (95% confidence interval 2.77-11.5, univariate) and 5.56 (2.62-11.8, multivariate) for the “genetic” model, and of 8.02 (3.52-18.3, univariate) and 19.8 (5.96-65.87, multivariate) for the “clinicogenetic” model during a 5-year follow-up.ConclusionsThe proposed 20-gene classifier can successfully separate the patients into two risk groups, and the two risk group had significantly different relapse rate and prognosis. This 20-gene classifier can provide better estimation of prognosis, which can help physicians to make better personalized treatment plans.
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.
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