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.
Highlights
Breast cancer is the second leading cause of cancer deaths in women, only to lung cancer resulting in 1 death among 38 women each year (6.8%) [1]
We have reported one 34-gene set and another 18-gene classifier in our prior studies that could partition the loco-regional recurrence in high risk patients from that of the low risk patients after mastectomy [15,16,17]
The first dataset GSE20685 [19] consists of gene expression profiles from 312 prospectively enrolled patients diagnosed with breast cancer and treated between 1991 and 2004 at the Koo Foundation Sun-Yat-Sen Cancer Center (KFSYSCC) and an additional 15 lobular breast carcinoma samples, collected between 1999 and 2004
Summary
Breast cancer is the second leading cause of cancer deaths in women, only to lung cancer resulting in 1 death among 38 women each year (6.8%) [1]. Breast cancer remains a very heterogeneous disease comprising a wide range of morphologic and biological features, clinical behavior, and treatment responses [2]. A patient’s prognosis is often judged by the available survival and recurrence rates, usually calculated from diagnosis. The risk of breast cancer recurrence, both local or distant. Is an important criterion that decides treatment courses for patients? Twenty to thirty percent of patients with an early breast cancer are susceptible to relapse [3]. Factors affecting recurrence/relapse, and the identification of genetic and histological factors that might affect subgroups of patients who continue to be at an increased risk of recurrence long after completing the standard course of treatment, during the first decade following diagnosis, are still an unmet clinical issue
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