A multiple breast cancer stem cell model to predict recurrence of T_1-3, N₀ breast cancer

Local 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.

In 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).

Four 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).

The 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.