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The Efficacy of Anthracycline-based Neoadjuvant Chemotherapy in Breast Cancer Patients

Author: WangXiaoLan
Tutor: JinFeng
School: China Medical University
Course: Surgical Oncology
Keywords: Breast tumor Neoadjuvant chemotherapy Human epidermal growth factor 2 receptor p53 Anthracycline
CLC: R737.9
Type: Master's thesis
Year: 2009
Downloads: 104
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Abstract


The purpose in recent years that breast cancer is a systemic disease, the treatment has been surgery-based treatment, from the local treatment of neoadjuvant chemotherapy (NAC) has become the standard treatment for locally advanced breast cancer. NAC that preoperative chemotherapy can reduce the clinical stage of the tumor, the opportunity to fight for breast-conserving surgery for breast cancer patients, and testing through the evaluation of the efficacy of the sensitivity of the tumor to chemotherapy, which provide guidance for the further treatment of postoperative . Breast cancer is a hormone-dependent tumors, subject to the regulation of estrogen and progesterone, the majority of breast cancer tissue has its own receptor (ER, PR) expression, and the proto-oncogene HER-2 expression in the presence of a considerable part of the breast tissue. For the correlation between ER, PR, HER-2 and p53 expression with NAC efficacy has been debated. The taxane has become the basis of drugs for the treatment of breast cancer, and Herceptin targeted therapy drugs used in clinical drug's status as a first-line treatment of breast cancer, but in China, the anthracene ring class of drugs should not be shaken. This study was a retrospective analysis of breast cancer estrogen receptor (ER) and progesterone receptor (PR), human epidermal growth factor receptor of -2 (HER2) and p53 protein expression and anthracene ring NAC drug efficacy The the correlation investigate, to provide guidance for clinical treatment. Materials and Methods, materials 1 clinical data to select the First Affiliated Hospital of China Medical University from January 2006 to June 2008, 40 cases of the initial treatment of breast cancer patients are women, aged 25 to 70 years, median age 50.4 years of age, ≤ 50 years of age 25 cases, 15 cases> 50 years of age; menopause before the 27 cases, 13 cases of postmenopausal; Ⅱ 7 cases, Ⅲ 33 cases; 39 cases of invasive ductal carcinoma, invasive lobular carcinoma. The system checks were not found to have distant metastases. Were confirmed by needle biopsy diagnosed with breast cancer before chemotherapy. Preoperative clinical stage according to the International Union Against Cancer (UICC) standard. 2, NAC program uses the CEF regimen were 37 cases, the CE program by three cases. The CEF regimen: Table A neomycin (EPI) 70 mg/m2, 5 - fluorouracil (5-FU) 600 mg/m2, cyclophosphamide (CTX 600 mg/m2) intravenously on day 1; CE programs: EPI 70 mg/m2, CTX 600 mg/m2. 21 d for a period. Predetermined NAC 3 ~ 4 cycles. Actual completion of two cycles were 30 cases, four cases of the three cycles ≥ 4 cycles were six cases. 3, the the efficacy assessment methods NAC before and after breast ultrasonography, measurement of maximum tumor diameter and vertical diameter of the breast X-ray, ultrasonography measured values ??were compared before and after the 33 patients with NAC, 7 patients with NAC before and after breast X-ray radiography measurement values for comparison. Efficacy divided into uniform standards developed by the WHO: complete remission (CR): complete disappearance of visible lesions, including axillary lymph nodes; partial remission (PR): tumor size more than 50%; stable (SD): less than 50% of tumor size or increase does not exceed 25%; large progress (PD): one or more lesions is increased by 25% or more, or the emergence of new lesions. Which CR is divided into pathologic complete response (pCR) and clinical remission (CCR). Surgery and then to evaluate the efficacy of pathological results. CR PR, SD PD is invalid. Method 1 immunohistochemistry SP method detection puncture specimens formalin-fixed, paraffin-embedded, 4μm thick sections, according to conventional immunohistochemistry SP method for ER, PR, c-erbB2 and p53 detection. ER, PR and p53 positive reactants brown particles located in the nuclei of diseased cells stained positive cells> 10% of the fixed-receptor-positive, ≤ 10% fixed-receptor-negative; c-erbB2 positioning in the cell membrane, the following criteria: no staining or less than 30% of tumor cells were stained for the negative (-),> 30% of the tumor cells with incomplete membrane coloring as weakly positive (),> 30% of the tumor cells there is a weak but The integrity of the cell membrane is colored positive (),> 30% of tumor cells stronger colored complete cell membrane was strongly positive (). In this study, the results of the immunohistochemical method (-) and () are seen as the HER-2 gene and no amplification, () and () further line FISH detection. Mouse anti-human ER, PR, p53, c-erbB2 monoclonal antibody and immunohistochemistry of SP kit were purchased white the Fujian Maixin Biotechnology Co., Ltd.. FISH detection of HER-2 gene amplification in the conventional horizontal slices xylene dewaxing graded ethanol hydration, acidic sodium sulfite process, protease digestion, HCl immersion, gradient ethanol dehydration, fixed in acetone at 56 ° C baked sheet, plus 10μl probe the working fluid in the tissue sections of denaturation at 73 ° C for 5 min in situ hybridization instrument after hybridization, 42 ° C wet box hybridized overnight (16 h), 50% formamide, citrate buffer, 0.1% NP-40 and 70% ethanol rinse, dark slide, DAPI-stained, Fengpian natural drying. Dark for 20 min and observed under a fluorescence microscope. Results Criteria: count 30 cells, the total number of the red signal statistics Ratio value (Ratio = 30 nuclei / total number of 30 nuclei green signal). Ratio <1.8 for negative results, suggesting that the sample without HER-2 gene amplification; Ratio> 2.2 for positive results prompted the samples HER-2 gene amplification; Ratio, choose to increase from 1.8 to 2.2 when the cell count to 100 or redo the FISH test to determine the final result. HER-2 FISHTM detection kit (American VYSIS) were purchased from Biological Technology Co., Ltd. Beijing Golden Bodhisattva Kerry. Results based on uniform standards developed by WHO in the NAC after assessment of all patients with a clinical response. 40 patients in CR, 4 patients (10%), which pCR those cases; PR, 26 patients (65%); SD, 9 patients (22.5%); PD, 1 (2.5%). HER-2 gene without amplification and p53 negative expression (P <0.05) associated with the high reactivity. Chemotherapy <4 cycles patients CR accounted for 5.88% of the patients with CR ≥ 4 cycles accounted for 33.33%, and between the two there is a statistically significant difference (P <0.05). The group obtained CR who are more than three cycles of chemotherapy. Conclusion anthracycline-based NAC group, HER-2 gene without amplification negative p53 protein expression is a predictor of the clinical response. Appropriate to increase the number of cycles of chemotherapy may increase the rate of complete remission.

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