Egfr Expression In Breast Cancer Research And Taxane Sensitivity

Now it is generally accecpted that breast cancer is a systemic disease. Taxans, which is one kind of chemo-agent often administered systemiclly, play an important role in the treatment of this disease, whether in adjuvant setting for pro venting recurrence or metastatsis after resection or rescue setting for treatment of advanced disease. The trying for searching an ideal molecular biologic marker that has predictive value for taxans is a hot topic in tumor-pharcology for a long time. The aim of this study is to find that kind of biomarker by analyzing clinical data of taxans in our department retrospectively. In order to verify the clinical results and to provide reasonable evidence-based information for the medical treatment of advanced breast cancer, related basic research in vitro is also conducted in cell level.Part one. Response outcomes of 211 cases of advanced breast cancer patients who had received taxans were analyzed by use of the WHO and RECIST criteria retrospectively simultaneously. The results showed that these two evaluation criteria have rather high grade of coincidance, Kappa= 0.853(95%CI: 0.779-0.927),p < 0.001.The RECIST criteria might be used clinically in place of WHO criteria due to the fact that evaluation of response by measurement of unidimension is relative easier than by bidimensions. As the primary leision and metastatic skin nodules or lymph nodes are ofter superficial, ultrasound and clinical examination are still the common used the methods for evaluation of target lesion. In this study, these two kind of methods were used in 74(35.1%) and 46(21.8%) cases of patients respectively. Therefor, besides the methods of CT and MRI, ultrasound and clinical examination are good complementary evaluation methods that should be recommended. Whether the threshold of 2cm for selection of evaluable lesion is reasonable need to be further discussed.Part two. In order to elucidate the relation of such biomarkers as ER, PR, HER-2, EGFR and BRCA-1 and the clinical response of taxans, biomarkers mentioned above were detected in 100 cases patients with advanced breast cancer who had used taxansas chemo agents previously. We found that the positive rate of these biomarkers are as follows:54%,46%,26%,42%,and 28%;HER-2 and EGFR, members of EGFR family that have high degree of homogeneity, did not have significant relativity(p=0.23).ER and HER-2 might be facts of significance when analyzed by univariate analysis(p=0.036 and 0.034),while analyzed by multivariate analysis, only ER was significant fact (p=0.019);No matter expressed independently or coexpressed, HER-2 and EGFR had nothing to do with the efficacy of taxans(p>0.05)Part Three.4 kind of human breast cancer cell lines, SK-BR-3CER Negative, HER-2 Overexpress) , MCF-7 ( ER Positive, HER-2 Negative) , MDA-MB-231 ( ER Negative, HER-2 Negative) , MDA-MB-453 (ER Positive, HER-2 Overexpress) , which have different levels of ER and HER-2 expression, were evaluated for response to docetaxel administered alone or in combination with Herceptin. The results showed that IC50 of docetaxel to 4 kind of cell lines were 3.65 0.72nmol/L, 7.54 + 0.62nmol/L, 54.7?.8nmol/L % 3.89?.46nmol/L, respectively. The status of HER-2 and ER might predict the sensitivity of these cell lines to docetaxel. For HER-2 overexpressed cell lines, docetaxel combine used with Herceptin had synthetic or additive effect and was superior to any of two drugs administered alone.