Neoadjuvant chemotherapy reduces the expression rates of ER, PR, HER2, Ki67, and P53 of invasive ductal carcinoma.

To analyze whether neoadjuvant chemotherapy (NAC) changes the expression rates of invasive ductal carcinoma (IDC) markers: estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), Ki67, and P53.This was a retrospective study of 112 IDC patients who underwent NAC (docetaxel+epirubicin/pirarubicin+cyclophosphamide) but without pathological complete response (pCR) in 2012 to 2013 at the First Affiliated Hospital of Chongqing Medical University. The IDC subtypes and tumor protein markers were analyzed by immunohistochemistry (IHC). Specific changes in tumor protein markers before/after NAC were compared.The decrease in the positive rate of Ki-67 was the most significant, from 75.9% before NAC to 41.1% after NAC (P < .001). The positive rate of HER2 decreased from 42.0% before NAC to 32.1% after NAC (P = .04). The positive rate of ER decreased from 66.1% before NAC to 56.2% after NAC (P = .04). Increased number of metastatic lymph nodes (P = .006) and body mass index (BMI) (P = .028) seemed to be related to conversion of PR (positive to negative). There was statistical association between the Ki-67 (positive to negative) with the age greater or equal to 50 (P = .015). The BMI greater or equal to 24 (P = .021), age greater or equal to 50 (P = .047), and blood type A (P = .038) were independently associated with conversion of P53 (positive to negative). The BMI greater or equal to 24 (P = .004), number of metastatic lymph nodes greater or equal to 1 (P = .029) and TNM stages I-II (P = .008) were statistically associated with change of HER2 (positive to negative).In patients without pCR, NAC leads to changes in Ki-67, HER2, and hormone receptor (HR) expression. Age, BMI, number of metastatic lymph nodes, and TNM stage are associated with some changes of markers.

Inhibition of Notch signaling pathway enhanced the radiosensitivity of breast cancer cells.

This study aimed to investigate the effect of inhibiting the Notch signaling pathway on the radiosensitivity of breast cancer cells. Human breast cancer cell lines (MCF-7 and T47D) were selected and treated with radiation of different doses. Cells were treated with Gamma secretase inhibitor (GSI) to analyze the effects of GSI on the Notch signaling, which were detected by Immunofluorescence assay, RT-qPCR, and Western blot analysis. Besides, Transwell assay, Scratch test, colony formation assay, MTT assay, and flow cytometry were conducted to show the effects of GSI on the invasion and migration, survival fraction, cell viability, and apoptosis of MCF-7 and T47D cells after radiation therapy. Moreover, cell transfection with a dominant negative mutant of RBPJ, the key transcription factor of Notch signaling pathway, were also applied to show the inhibition of Notch signaling pathway. Initially, we found that the 4 Gy radiation activated Notch signaling pathway, and enhanced the invasion and migration of MCF-7 and T47D cells. However, GSI inhibited the Notch signaling pathway, and reversed the enhancement of radiation on the migration and invasion, promoted the enhancement of apoptosis and inhibition of proliferation of MCF-7 and T47D cells induced by radiation. Except that, we also determined that GSI and dnRBPJ suppressed the upregulation of Notch signaling after radiation therapy. Our study demonstrated that inhibition of the Notch signaling pathway enhanced the radiosensitivity of breast cancer cells, which may provide evident for a beneficial adjuvant therapy in the breast cancer treatment.