In determining the cell biological behavior of breast cancer in responding to P4 treatment

However, both mPRa expression level and mPRa-HiEx rate were significantly lower or moderately lower in patients with TNM 4 stage. According to our best knowledge, our study provides the first line of indication that expression of mPRa may be associated with breast cancer TNM stage. Further study on breast cancer prognosis and mPRa expression would be meaningful in clinic.The role of progesterone signaling in breast cancer development has attracted substantial interest, but there also remains controversy. It is believed that the physiological actions of P4 is mediated through nuclear PR. However, it has been observed for many years that part of the physiological actions of P4 cannot be explained by its genomic activity through nuclear PR. Substantial evidence indicates that non-genomic steroid signaling, including P4 signaling, is mediated through membrane or cytoplasmic-localized classic steroid receptors, such as mPRa. So far, research has been very limited on the physiological activity of mPRa and virtually no study has investigated its activity in breast cancer pathogenesis. Depending upon the experimental cell model system, cell context, and duration of treatment, P4 can elicit either proliferative or antiproliferative effects on breast cancer cells in vitro. For example, P4 induces cell growth and migration of T47D, but inhibits the cell proliferation of MDA-MB468 cells, a human BPBC or TNBC cell line with strong mPRa protein expression. It seems that the status of breast cancer triple markers, ER, PR, and HER2, plays an essential role in determining the cell biological behavior of breast cancer in responding to P4 treatment. In this study, we Seratrodast demonstrated a negative correlation between mPRa and ER; and the significance of the relationship between mPRa and ER remained after adjusting for age at diagnosis and/or TNM stage, indicating strong correlations existed in these receptors, even though the percentages of cancers with mPRa-HiEx marginally differ by ER status. To confirm these findings, further study with larger sample sizes is essential. Due to high throughput techniques, many novel biomarkers with prognostic and predictive values were reported in recent years, but very few of them have been validated and adopted for clinical use. According to “the American Society of Clinical Oncology 2007 update of Recommendations for the Use of Tumor Markers in Breast Cancer”, only three biomarkers, including ERa, PR and HER2 expression and/or amplification, are recommended for routine clinical use for every patient with primary invasive breast cancer. Based upon the gene expression profiles, Perou et al Halothane classified breast cancer into four broad distinct groups: luminal A and B, HER2positive, normal-breast-like and basal phenotype breast cancer. This classification, however, very closely corresponds to the classifications identified based on ER/PR/HER2 status.