| Background:Breast cancer is a malignant tumor that is a serious threat to women's health.In recent years,epidemiological data show that the incidence of breast cancer is on the rise,and it is now the first female malignant tumor.Around 1.7 million women are diagnosed with breast cancer each year and about 500,000 die from breast cancer,according to GLOBOCAN2012,released by the world health organization's center for international cancer research.According to the data from China's national cancer center,the national average incidence is about 37.86/10.In 2012,it was estimated that 272 700 breast cancer cases were newly diagnosed among women and approximately 61 500 women died of breast cancer in China.Research data show that 5-year survival rate of patients with clinical stage ? and ? can reach 85%?90%,the 5-year survival rate of patients with stage ? is about 50%,the 5-year survival rate of patients with stage ? is about 10%?18%.With the improvement of people's living standard and the strengthening of health awareness,now more and more clinical cases of early breast cancer are found,and the early diagnosis and early treatment of breast cancer has important significance for improving the prognosis of patients.The treatment of breast cancer include surgery,chemotherapy,radiotherapy,endocrine therapy,molecular targeted therapy and other means,with the progress of the comprehensive treatment,the prognosis of breast cancer is further improved.So,whether in foreign or domestic,despite the high incidence of breast cancer death rates are falling,it is not only benefited from the establishment of the female breast cancer screening and early detection system,but also benefited from the development of molecular biology technology and the improvement of the comprehensive level of diagnosis and treatment standardization in recent years.However,breast cancer,as a highly heterogeneous systemic disease,may occur distant metastasis at the onset of the disease,thus affecting the survival and prognosis of patients.With the improvement of molecular biology,we know that the prognosis of breast cancer is not only related to the staging of disease,its biological behavior is more important for the treatment response and prognosis.For example,type luminal A breast cancer with low-risk is not sensitive to chemotherapy,while endocrinotherapy is better.It can't avoid distant metastasis within 2 years after surgery in some early-stage breast cancer with Her-2 overexpression and triple-negative breast cancer,even with standardized treatment.In the long term,the clinical histopathological features are the important basis for the treatment of breast cancer.But in the era of molecular level,traditional histologic classification cann't meet the requirements of cancer research and diagnosis and treatment,it is the precondition for individualized precise treatment to accurately grasp the molecular typing characteristics of breast cancer patients.The chemotherapy plays an important role in breast cancer treatment system,whether received chemotherapy or not,it relys on the patient's clinicopathological features and molecular typing,it is a complex process to examine the timeliness and effectiveness of chemotherapy.For example,it could not directly determine whether the chemotherapy is effective because the primary tumor is removed in the postoperative adjuvant chemotherapy,and the treatment regimen could only be maked according to the existing evidence-based medical evidence.And in the process of neoadjuvant chemotherapy,it takes weeks or months to see whether the tumor shrink.If the chemotherapeutic drug is not effective,it may delay surgical treatment,and some molecular indicators are needed to monitor and respond to chemotherapy in a timely manner,so certain molecular indicators are needed to monitor and respond to chemotherapy effectively.There are a lot of studies trying to find specific indicators of the efficacy of neoadjuvant chemotherapy,such as serum CEA,CA153,etc,but the final results are not so good.With the development of genomics and precise medical liquid biopsy is becoming a hot spot of recent research.The more mature liquid biopsy to detect objects including circulating tumor cells(circulating tumor cells,CTCs),circulating tumor DNA(circulating tumor DNA,ctDNA),etc.With the in-depth study of liquid biopsy,its advantages,such as noninvasive,rapid,accurate and overcoming tumor time or spatial heterogeneity,have aroused great enthusiasm in global scientific research,clinical and industry.The clinical application fields of liquid biopsy may include diagnosis(early identification and monitoring of residual lesions),prediction(assessment of tumor heterogeneity,monitoring dynamic changes of tumor,distinguish therapy target gene,early evaluation of treatment response,real-time assessment of tumor drug resistance)and prognosis(factors detection,tumor load change),but as a new technology the liquid biopsy is still the main used in scientific research,exploration,large-scale clinical application needs further evidence to support and improve.There are a large number of reports about CTCs and recurrence of breast cancer diagnosis,treatment and monitoring.We hope to find the suitable CTCs detection method and application range.Let the new technology of CTCs liquid biopsy serve the clinic better.There are some advantages on the traditional evaluation indicators of breast cancer prognosis and neoadjuvant chemotherapy efficacy,such as clinical popularity,but there is not enough precision.To explore the related factors affecting the prognosis of breast cancer,we analyzed the clinical data of early-stage breast cancer in order to guide the individualized treatment through the traditional clinicopathological features.And we want to find suitable predictors which can forecast the efficacy of neoadjuvant chemotherapy for basic-level hospitals through the analysis of the curative effect of neoadjuvant chemotherapy in locally advanced breast cancer and predictive value of circulating tumor cells for evaluating short-and long-term efficacy of neoadjuvant chemotherapy chemotherapy for breast cancer,and patients with breast cancer can receive more accurate treatments.Part 1 The relationship between prognosis and clinicopathological features in breast cancerAims:To analyze the risk factors of recurrence and metastasis of early breast cancer and provide basis for individualized treatment of early breast cancer.Materials and methods:The clinical,pathological and immunohistochemical data of 650 cases with early breast cancer from 2008 to 2011 was analyzed and the recurrence and metastasis was observed by follow-up.The disease-free survival rates was analyzed by Kaplan-Meier method and the possible risk factors were compared by Log-rank test.Then the risk analysis was executed by Cox model.Results:The 5-year disease-free survival rates of these patients was 91.7%.Univariate analysis showed that tumor stage,size,lymph node metastasis,histological type,HER-2 and Ki-67 can significantly affect the disease-free survival rates(P<0.05);while postoperative chemotherapy or radiotherapy or hormonal therapy can reduce disease-free survival rates(P<0.05).COX regression analysis showed that these factors could affect 5-year disease-free survival rates(P<0.05).Conclusion:Late tumor staging,tumor large,lymph node-positive,invasive carcinoma,HER-2 positive and Ki-67 overexpression are risk factors for recurrence and metastasis of early breast cancer.Part 2 Clinical study of neoadjuvant chemotherapy for breast cancer with different pathological featuresAims:To investigate the clinical efficacy of docetaxel plus Epirubicin and Cyclophosphamide as the neoadjuvant chemotherapy(TEC)regimen in the treatment of locally advanced breast cancer,and find molecular indicators that affect the efficacy of neoadjuvant chemotherapy.Materials and methods:110 cases of patients with locally advanced breast cancer were selected from February 2008 to December 2016 in our hospital,the patients were treated with TEC regimen for neoadjuvant chemotherapy,the clinical efficacy and toxicity were observed.Results:Among 110 patients,twelve patients(10.9%)achieved clinical complete response,eighty-four patients(76.4%)in clinical partial response,nine patients(8.2%)in clinical stable disease,five patients(4.5%)in progressive disease,and the total clinical efficiency reached 87.3%.The main side effects were bone marrow suppression,gastrointestinal reaction and hair loss.Conclusion:TEC neoadjuvant chemotherapy is applied to local advanced breast cancer with high clinical efficiency,triple-negative breast cancer benefits more from neoadjuvant chemotherapy.Part 3 Predictive value of circulating tumor cells for evaluating short-and long-term efficacy of neoadjuvant chemotherapy for breast cancerAims:The present study investigated the role of circulating tumor cells(CTCs)counts in predicting the short-and long-term efficacy of neoadjuvant chemotherapy for breast cancer(BC).Materials and methods:Peripheral venous blood was extracted from 187 patients with breast cancer from our hospital.CTCs were measured by flow cytometry.Spearman's correlation analysis was performed to examine the correlation between the efficacy of chemotherapy and CTC counts.A receiver operating characteristic(ROC)curve was plotted to estimate the predictive value of CTC counts.The Kaplan-Meier method was employed to calculate disease-free survival(DFS)and overall survival(OS).Cox regression analysis was used to determine risk factors for prognosis of BC.Results:Complete response(CR)+ partial response(PR)was achieved by 65.8%of BC patients.After chemotherapy,CTC counts were decreased in both the CR + PR and SD + PD groups.Spearman's correlation analysis indicated that CTC counts before chemotherapy were positively correlated with clinical response to chemotherapy(r=0.45,P<0.05).The Kaplan-Meier method and Cox regression analysis indicated that tumor node metastasis(TNM)staging,lymph node metastasis(LNM),ki-67,endocrine therapy,and CTC counts were risk factors for prognosis of BC.Conclusion:These findings indicate that BC patients with CTCs?8 exhibited poor response to chemotherapy and poor OS.CTC counts can serve as an indicator in predicting short-and long-term efficacy of neoadjuvant chemotherapy for BC. |
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