ER, PR, C-erbB-2 And Their Study Of Sensitivity To Anticancer Drugs In Breast Cancer

Background and ObjectivesBreast cancer is one of malignant disease which poses a great threat to women's life and health. Adjuvant chemotherapy for the treatment of breast cancer is an effective method in improving the prognosis, which is an important measure for comprehensive treatments for breast cancer. malignant tumors have strong heterogeneity. Various chemotherapy have obviously individual differences in medicines, The sensitivity assay for anticancer drugs may examine the sensitivity of cancer cells to chemotherapeutic agents, which can directly acquire experimental data. This can guide the application of drugs for clinical personalization. Due to the limitations of tumor chemosensitivity assay carried on, establishing relationships of breast cancer genotype and anticancer drugs, we can indirectly select medicines based on clinical cancer susceptibility, this can provides a way to personalized chemotherapy for breast cancer.Genotype is divided into LuminalA of breast cancer:ER(+), PR(+), C-erbB-2 (-),and LuminalB:ER (+), PR (+), C-erbB-2 (+), Basal-like:ER (-), PR (-), C-erbB-2 (-) and ERBB2 (+):ER (-), PR (-), C-erbB-2 (+). At present, tumor chemosensitivity assay was carried on some study in breast cancer, but no related studies of ER, PR, C-erbB-2 and anticancer drugs sensitivity in chemotherapy for breast cancer.ER can be closely integrated with the cell ligand, which is highly specific glycoprotein cells. A small quantity of ligand can activate ER pathway effectively. ER depend on estrogen effect to induce gene transcription and promote proliferation of tumor cells.PR is end products, which can be affected by estrogen. Estrogen promotes the synthesis of PR. ER expression levels are important factors which affect PR expression, the higher the positive degree of ER, the more PR expression, activity and the pathway of ER is a key factor for PR expression.C-erbB-2 is a proto-oncogene, which plays a decisive role in growth factor signaling pathways and controls normal cell growth and differentiation. Growth factors and C-erbB-2 receptor on the cell surface can activate intracellular tyrosine kinase, and then cause phosphorylation of tyrosine itself, which may keep triggering a cascade of chain reactions. The signals through the cell membrane and the stromal cells spreads into the nucleus, which activate C-erbB-2 gene, accelerate mitosis, regulate cell growth and promote the proliferation and differentiation of malignant tumor, its overexpression prompts C-erbB-2 gene amplification infinitely, and then promotes C-erbB-2 gene transcription, increases replication, and keeps enhancing C-erbB-2mRNA translation level and C-erbB-2 receptors synthesis and overexpression, this can induce signaling pathways activated through ligand binding, keep triggering the growth and differentiation of tumor cell infinitely. C-erbB-2 is also a drug-resisted gene. The higher the positive rate of C-erbB-2, the stronger the cancer cells resists. Because genotyping of breast cancer may affect the biological behavior of tumors and the sensitivity of chemotherapy. Therefore, depending on test of tumor susceptibility, establishing relationship of ER, PR, C-erbB-2 and the anti-tumor drugs, and then guided the selection of clinical personalized medicine. Chemotherapy will be more focused treatment.Materials and Methods1 SpecimenBreast surgical treatment of 69 hospitalized patients were collected from July 2008 to December 2009 at the Second Affiliated Hospital of Zhengzhou University. Intraoperative frozen section and routine pathological examination confirmed breast cancer after radical mastectomy or breast conserving surgery. We will detect ER, PR, C-erbB-2 simultaneously. Tumor specimens were immediately sent to the laboratory for the following treatment to avoid specimens contamination,①We use culture medium of RMPI-1640 to wash specimens three times in 15ml culture tubes;②We add with amount of RMPI-1640 involved 100U/ml penicillin and streptomycin to immerse specimens at twenty minutes, after completion of the deal, under the principle in sterile, clipping specimens to process the next step.2 Research methodsThe specimens were made into single cell suspension, then we examine cells degrees and counting, adjust the cell concentration, establish the experimental group, control group and cell control group. Various drugs are diluted to experimental liquids. We may add the liquids to 96 holes training board to cultivate specimens four days later, and add again 0.5% MTT cultivating and dissolved. We axamine absorbency in the microplate reader to calculate inhibiting rate of tumor cells in every hole.3 Evaluation Criteria5PPC solution serves as the concentration of drug sensitivity. Criteria of evaluation are that high sensitivity of tumor inhibiting rate is above 50%, sensitivity of tumor inhibiting rate is between 30%-50%, inhibiting rate of tumor cells of resistance is below 30%.4 Statistic analysisIn this study, All the data were expressed by (x±s). The statistical software SSPS17.0 for windows was exploited to analyze data. Which was processed the test of homogeneity of variance and normality, Deviation and difference were compared using the one way ANOVA and LSD test between each group, The different significance is judged by P<0.05.ResultsThe four specimens of ER(+), PR(+), C-erbB-2(-), ER(+), PR(+), C-erbB-2(+), ER(-), PR(-), C-erbB-2(-) and ER(-), PR(-), C-erbB-2(+) do not reflect the significant difference in fluorouracil(P>0.05). The ER(+), PR(+), C-erbB-2(-) have an advantage over ER(+), PR(+), C-erbB-2(+), ER(-), PR(-), C-erbB-2(-) and ER(-), PR(-), C-erbB-2(+) in methotrexate(P<0.05). The ER(+), PR(+), C-erbB-2(-) have an advantage over ER(-), PR(-), C-erbB-2(-) and ER(-), PR(-), C-erbB-2(+) in adriamycin(P<0.05); The ER(+), PR(+), C-erbB-2(-) have an advantage over ER(-), PR(-), C-erbB-2(+) in epirubicin (P<0.05). The ER(+), PR(+), C-erbB-2(-) have an advantage over ER(+), PR(+), C-erbB-2(+), ER(-), PR(-), C-erbB-2(-) and ER(-), PR(-), C-erbB-2(+) in paclitaxel(P<0.05).Conclusions1. The experiments shows that genotypes are correlate with sensitivity of chemotherapy in breast cancer. ER(+), PR(+), C-erbB-2(-), ER(+), PR(+), C-erbB-2(+) and ER(-), PR(-), C-erbB-2(-) three types of cells have the same orders in various inhibiting rates in anticancer drugs:PTX> EPI> ADM> 5-FU> MTX. ER(-), PR(-), C-erbB-2(+) cells has a different inhibiting effect on a variety of anticancer, its sequence follows as:PTX> ADM> EPI> 5-FU> MTX.2. Different genotypes of breast cancer have different inhibiting rates to the same chemotherapeutic drug, which suggests that they have different chemotherapeutic benefit. Paclitaxel, doxorubicin, epirubicin, fluorouracil and methotrexate have the highest inhibiting effect in the ER(+), PR (+), C-erbB-2(-). All five drugs have the lowest inhibiting effect in the ER(-), PR(-), C-erbB-2(-). Based on the different genotypes, we choose sensitive drugs so as to obtain maximum benefit of treatment and achieve individualized treatment for breast cancer.