Gene expression markers predicting hematogenous metastasis for HER2-negative breast cancer treatment with taxane-containing neoadjuvant chemotherapy

Background. Neoadjuvant chemotherapy (NAC) is a common treatment option for patients with triple-negative and HER2-positive breast cancer (BC) subtypes. The use of NAC in HER2-negative breast cancer is a matter of debate. For patients with HR+/HER2-breast cancer, the choice of NAC is still based on clinical and pathological characteristics rather than on biomarkers with a certain clinical value, in contrast to adjuvant therapy, where gene expression signatures are widely used for decision-making. Therefore, it is imperative to evaluate not only the efficacy of NAC but also to identify markers for disease prognosis in this specific patient group.

Aims. In this work, we studied the changes in the expression profile of HER2-negative breast tumors when using taxane-containing NAC regimens.

Material and methods. The material used was paired biopsy samples before treatment and tumor tissue (after NAC) for each patient. The expression landscape of the tumor was assessed using whole transcriptome microarray analysis using Clariom™ S Assay, human microarrays (Affymetrix, USA). Overall and metastasis-free survival curves for patients included in the study were constructed using the Kaplan-Meier method. The obtained result was validated on an independent sample.

Results. As a result, a comparison of the expression profile of the tumor of patients before and after NAC with taxane-containing regimens determined that the expression level of the PODXL2 gene in the tumor before treatment, depending on the response to therapy, and the level of expression of the NR2E1 and TMEM98 genes in the tumor after NAC, depending on the status of hematogenous metastasis, statistically significantly correlate with the OS and RFS of patients, respectively.

Conclusions. Potential expression markers of an objective response to the applied treatment and prediction of the occurrence of hematogenous metastasis of HER2-negative breast tumors were identified when prescribing taxane-containing treatment regimens.

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