Breast cancer is the most common neoplasm worldwide and is the leading cause of cancer deaths among women. Triple-negative breast cancer (TNBC) is the most aggressive subtype with the lowest 5-year survival rates accounting for 12-18% of all breast cancers. TNBCs have a much higher recurrence and metastasis as a result of not being eligible for current treatment options due to the lack of estrogen, progesterone receptor, and human epidermal growth factor receptor 2 [1]. This aggressive cancer contributes to the overall shortened survival of patients diagnosed with TNBC [2].
Considering the absence of molecular targets, neoadjuvant chemotherapy (NAC) remains the standard of care for patient treatment. However, the effectiveness of treatment is unpredictable, as patients frequently develop resistance. For this reason, there is a growing need to develop novel non-invasive molecular predictive approaches for this disease [3]. It has become evident that the development of TNBC chemoresistance is based on the elaborate interplay of the tumor microenvironment, drug efflux, and cancer stem cells. Alterations of multiple signaling pathways govern these interactions [2]. Recent evidence from clinical trials and preclinical studies have demonstrated a pivotal role of the STAT3 (signal transducer and activator of transcription 3) signaling pathway in the initiation, progression, and metastasis of TNBC [3].
The aim of this study was to evaluate the expression of STAT3, ALDH1A1, NFIB, UPF3A, BCL-2, and R-RAS-2 genes in serial plasma samples before and after NAC. Gene expression changes were used to determine associations with clinical features of TNBC patients and to analyze STAT3, ALDH1A1, NFIB, UPF3A, BCL-2, and R-RAS-2 expression as potential biomarkers for predictive purposes.
In this study, we used reverse transcription quantitative PCR to determine STAT3, ALDH1A1, NFIB, UPF3A, BCL-2, and R-RAS-2 expression in paired 122 blood plasma samples of TNBC patients before and after NAC. We determined that a combination of expression changes of STAT3, BCL-2, and R-RAS-2 could be used as a predictive biomarker panel to determine TNBC patients that show a more positive response to NAC (p=0.0012, p=0.0098 and p<0.0001, respectively).
Overall, understanding how the expression changes of these genes influence the course response to NAC in TNBC patient plasma potentially could be used as non-invasive molecular biomarkers for treatment effectiveness.