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진스웰 BCT

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Clinical Validation

GenesWell BCT was validated for early-stage-stage breast cancer patients with HR+, HER2-, pN0/1.

Prognostic Ability

To validate the prognostic Ability of GenesWell BCT, we compared distant metastasis free survival(DMFS), disease-free survival(DFS) and overall survival(OS) between low-risk group and high-risk group.

Difference between two groups was found as the patients classified into a low-risk group had a higher survival rate than those in a high-risk group.

  • 10-year DMFS

    10-year DMFS

    We compared the probability of survival without distant metastasis in 10 years between two groups. Low-risk group had a 22.5% higher distant metastasis free survival rate than high-risk group.

  • 10-year DFS

    10-year DFS

    We compared the probability of survival without recurrence in 10 years between two groups. Low-risk group had a 30.1% higher distant free survival rate than high-risk group.

  • 10-year OS

    10-year OS

    We compared the probability of survival in 10 years between two groups. Low-risk group had a 21.9% higher survival rate than high-risk group.

A new molecular prognostic score for predicting the risk of distant metastasis in patients with HR+/HER2− early breast cancer
Gong, G. et al.
Scientific Reports | 2017

To make an optimal treatment decision for early stage breast cancer, it is important to identify risk of recurrence. Here, we developed and validated a new prognostic model for predicting the risk of distant metastasis in patients with pN0-N1, hormone receptor-positive, HER2-negative (HR+/HER2−) breast cancer treated with hormone therapy alone. RNA was extracted from formalin-fixed, paraffin-embedded tumor tissues and gene expression was measured by quantitative real-time reverse transcription-PCR. The relative expression of six novel prognostic genes was combined with two clinical variables (nodal status and tumor size) to calculate a risk score (BCT score). In the validation cohort treated with hormone therapy alone, the 10 year rate of distant metastasis in the high-risk group (26.3%) according to BCT score was significantly higher than that in the low-risk group (3.8%) (P < 0.001). Multivariate analysis adjusted for clinical variables revealed that BCT score is an independent predictor of distant metastasis. Moreover, the C-index estimate revealed that BCT score has a prognostic power superior to that of prognostic models based on clinicopathological parameters. The BCT score outperforms prognostic models based on traditional clinicopathological factors and predicts the risk of distant metastasis in patients with HR+/HER2− early breast cancer.

Chemotherapy Benefits

It has been identified that chemotherapy benefits are different depending on risk groups classified by GenesWell BCT. Not all patients benefit equally from adjuvant chemotherapy. It is tailored specifically for each patient’s unique situation. Patients within the low-risk group (BCT score<4) showed 96.0%(92.5% ~ 99.7%) in survival rate within the 10-year period when only hormone therapy was given, and exhibited 96.4%(92.5% ~ 100%) when hormone therapy was given with chemotherapy.

There was only a 0.4% difference in survival rate between the two groups which means that there was no statistically significant difference(p-value=0.003, log-rank test). In patients within the high-risk group (BCT score≥4), they showed 65.4% (47.3%-90.5%) in survival rate within the 10-year period when only hormone therapy was given, and exhibited 91.9% (84.5%-99.9%) when hormone therapy was given with chemotherapy. There was a statistically significant difference in the survival rate within 10 years by 26.5% between patients with and without chemotherapy (p-value=0.003, log-rank test).

BCT score predicts chemotherapy benefit in Asian patients with hormone receptor-positive, HER2-negative, lymph node-negative breast cancer
Kwon. et al.
PloS one | 2018

The Breast Cancer Test (BCT) score has been validated for its ability to predict the risk of distant metastasis in hormone receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative early breast cancer. This study aimed to examine the value of the BCT score for predicting the benefit of adjuvant chemotherapy for Korean women with hormone receptor-positive, HER2-negative, lymph node-negative breast cancer. The study included 346 patients treated with either hormone therapy alone (n = 203) or hormone therapy plus chemotherapy (n = 143), and compared patient survival between the two treatment groups. The effect of BCT score on patient survival by treatment group was assessed using Cox proportional hazards models. Based on the results, the BCT score was prognostic for distant metastasis-free survival and breast cancer-specific survival in the hormone therapy alone group. There was no significant difference between the treatment groups in terms of 10-year distant metastasis-free survival in the overall patient population. However, when patients were classified as low risk (n = 266) and high risk (n = 80) according to the BCT score, addition of adjuvant chemotherapy to hormone therapy for patients classified as BCT high-risk group led to a significant improvement in 10-year distant metastasis-free survival, from 65.4% to 91.9% (hazard ratio, 0.18; 95% confidence interval, 0.05–0.64; P = 0.003); in contrast, there was no benefit for the BCT low-risk group. The stratification of patients according to the BCT score also identified clinically high-risk patients who may not benefit from chemotherapy. Results were similar for breast cancer-specific survival. In conclusion, the BCT score was not only of prognostic value but was also a predictor of chemotherapy benefit for Korean patients with hormone receptor-positive, HER2-negative, lymph node-negative breast cancer.

9 genes

Through broad-based data analysis of breast cancer patients, GenesWell BCT selected 9 genes that represent the difference of survival rate between two risk groups(high/low). It includes a total of nine genes: five proliferation genes (UBE2C, TOP2A, RRM2, FOXM1, MKI67), one immune gene (BTN3A2), and three reference genes (CTBP1, CUL1, UBQLN1).

Prognostic genes

GenesWell BCT uses 5 proliferation-related genes associated with the promotion of cancer cell proliferation and 1 immune response-related gene associated with the inhibition of cancer cell proliferation.

Through accurate prognostic gene discovery, the probability of recurrence or distant metastases can be more accurate.

Reference genes

Reference genes are indispensable in tests that estimate expression level through relative comparisons. In order to confirm whether the expression level of the target gene is high or low, it is necessary to be preceded to confirm whether the reference genes are constantly expressed.

We conducted a reference gene derivation study suitable for the GenesWell BCT test to select a new standard gene that can accurately compare and analyze the expression of breast cancer prognostic genes.

GenesWell BCT study
- Reference Genes

Identification of Novel Reference Genes Using Multiplatform Expression Data and Their Validation for Quantitative Gene Expression Analysis
Kwon et al.
PLoS ONE | 2009

Normalization of mRNA levels using endogenous reference genes (ERGs) is critical for an accurate comparison of gene expression between different samples. Despite the popularity of traditional ERGs (tERGs) such as GAPDH and ACTB, their expression variability in different tissues or disease status has been reported. Here, we first selected candidate housekeeping genes (HKGs) using human gene expression data from different platforms including EST, SAGE, and microarray, and 13 novel ERGs (nERGs) (ARL8B, CTBP1, CUL1, DIMT1L, FBXW2, GPBP1, LUC7L2, OAZ1, PAPOLA, SPG21, TRIM27, UBQLN1, ZNF207) were further identified from these HKGs. The mean coefficient variation (CV) values of nERGs were significantly lower than those of tERGs and the expression level of most nERGs was relatively lower than high expressing tERGs in all dataset. The higher expression stability and lower expression levels of most nERGs were validated in 108 human samples including formalin-fixed paraffin-embedded (FFPE) tissues, frozen tissues and cell lines, through quantitative realtime RT-PCR (qRT-PCR). Furthermore, the optimal number of nERGs required for accurate normalization was as few as two, while four genes were required when using tERGs in FFPE tissues. Most nERGs identified in this study should be better reference genes than tERGs, based on their higher expression stability and fewer numbers needed for normalization when multiple ERGs are required.

GenesWell BCT study
- Prognostic Genes

A prognostic model for lymph node-negative breast cancer patients based on the integration of proliferation and immunity
Oh et al.
Breast Cancer Res Treat | 2011

A model for a more precise prognosis of the risk of relapse is needed to avoid overtreatment of lymph node-negative breast cancer patients. A large derivation data set (n = 684) was generated by pooling three independent breast cancer expression microarray data sets. Two major prognostic factors, proliferation and immune response, were identified among genes showing significant differential expression levels between the good outcome and poor outcome groups. For each factor, four proliferation-related genes (p-genes) and four immunity-related genes (i-genes) were selected as prognostic marker in early breast cancer. The p-genes showed a predominantly negative correlation with survival time, while the i-genes showed a positive correlation, reflecting the beneficial effect of the immune response against deleterious proliferative activity.

GenesWell BCT Clinical Trials

We continue to conduct clinical trials for GenesWell BCT in breast cancer patients to build clinical evidence.
To date, more than 2,500 breast cancer samples have been tested for GenesWell BCT-related clinical trials.