Abstract
BackgroundLocal or distant relapse is the key event for the overall survival of early-stage breast cancer after initial surgery. A small subset of breast cancer cells, which share similar properties with normal stem cells, has been proven to resist to clinical therapy contributing to recurrence.MethodsIn this study, we aimed to develop a prognostic model to predict recurrence based on the prevalence of breast cancer stem cells (BCSCs) in breast cancer. Immunohistochemistry and dual-immunohistochemistry were performed to quantify the stem cells of the breast cancer patients. The performance of Cox proportional hazard regression model was assessed using the holdout methods, where the dataset was randomly split into two exclusive sets (70% training and 30% testing sets). Additionally, we performed bootstrapping to overcome a possible biased error estimate and obtain confidence intervals (CI).ResultsFour groups of BCSCs (ALDH1A3, CD44+/CD24−, integrin alpha 6 (ITGA6), and protein C receptor (PROCR)) were identified as associated with relapse-free survival (RFS). The correlated biomarkers were integrated as a prognostic panel to calculate a relapse risk score (RRS) and to classify the patients into different risk groups (high-risk or low-risk). According to RRS, 67.81 and 32.19% of patients were categorized into low-risk and high-risk groups respectively. The relapse rate at 5 years in the low-risk group (2.67, 95% CI: 0.72–4.63%) by Kaplan-Meier method was significantly lower than that of the high-risk group (19.30, 95% CI: 12.34–26.27%) (p < 0.001). In the multiple Cox model, the RRS was proven to be a powerful classifier independent of age at diagnosis or tumour size (p < 0.001). In addition, we found that high RRS score ER-positive patients do not benefit from hormonal therapy treatment (RFS, p = 0.860).ConclusionThe RRS model can be applied to predict the relapse risk in early stage breast cancer. As such, high RRS score ER-positive patients do not benefit from hormonal therapy treatment.
Highlights
Local or distant relapse is the key event for the overall survival of early-stage breast cancer after initial surgery
Wang D et al identified PROCR as a marker of multipotent mammary stem cells. They found that PROCR-positive mammary cells exhibited epithelial-to-mesenchymal transition (EMT) characteristics, and had high tumorigenesis ability in vivo, which suggested that PROCR-positive mammary cells might be one of the progenitor populations for breast Cancer stem cell (CSC) (BCSCs) [24]
In a medium cohort of patients in previous studies, these findings revealed that ALDH1A3, PROCR, ITGA6+, ITGA6+/EpCAM− and ITGA6−/ EpCAM+ were correlated with reduced relapse-free survival (RFS) or overall survival of these breast cancer patients [35,36,37]
Summary
Local or distant relapse is the key event for the overall survival of early-stage breast cancer after initial surgery. Recent advancements have further divided this heterogeneous disease into distinct subgroups by gene expression profiling (GEP) assays, among other methods, several intriguing findings revealed that a small subset of cells isolated from different subgroups of breast cancers exhibit remarkable similar biological behaviours. These subset of cells were defined as cancer stem cells (CSCs) and reported to be responsible for the heterogeneity. PROCR promotes tumour metastasis in cancer cell lines [33, 34]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
