Analysis Of Response To Neoadjuvant Chemotherapy And Prognosis Of Breast Cancer Patients Accepting Neoadjuvant Chemotherapy

Backgroud:Breast cancer is the most common malignant tuomor in female,25% of primary cancer is breast cancer, and it contribute to 15% of death in women with cancer, so obviously, breast caner keep the first place of mortality, which heavily threatens lives and health of women, and affects economics、society、family and psychological health of women.In China more than 1.6 million people being diagnosed and 1.2 million dying of the disease each year, althogh the systemic treatment of brast cancer is now well established, and more and more breast cancer patients benefit from it, but the mortality due to breast cancer is still high.As a part of the system, neoadjuvant chemotherapy(NAC) is widely used in locally advanced breast cancer. Moreover, preoperative therapy can make many patients have a choice to have breat-conserving surgery. The significance of neoadjuvant chemotherapy include:screening sensitive regimen of chemotherapy, elimating or decreasing micrometastatic lesion, preventing distant metastasis, etc.At the same time, it can provide prognostic information that will guide the choice of treatments to maximize the degree of respose. For example, many research consider that patients who get pathological complete remission (pCR) have longer disease free survival (DFS) and overall survival (OS), reduction of ki67 percentage after NAC predict better survival benefit. At present, NAC can get the efficiency of 60-90%,and about 20% of the patients achieve pCR after an appropriate NAC regimen. However, it is still can’t be avoided that disease develops in a number of patients, and pCR rate is still too low. So this research aims at finding information that predict the prognosis of patients who accept NAC, analyzing the survival benefit of NAC patients, guiding the individualized treatment for breast cancer.Objects:1. To find the predictive indicators that have close relationship to response of neoadjuvant chemotherapy;2. To analyze the survival of NAC patients, confirm the prognostic value of pCR, compare the survival benefit between NAC patients and non-NAC patients.Methods:Review the patients that accept systemic treatment in The Second Hospital of Shandong University from May 2004 to January 2014, consult the medical records of the patients to make retrospective review and collect clinical factors including age, height, weight, menstrual status, fertility circumstance, lactation status, hypertension history, cardiac disease history, diabetes history, family history of breast cancer, history of breast benign diseases, characteristics of tumor, axillary and supraclavicular nodes status, operation methods, first day volume of drainage,pathological types, histological grades, immunohistochemical(IHC) indicators of biopsy and surgery, tumor cutting area, metastatic lymph nodes, change of IHC indicators after NAC,chemotherapy, radiotherapy, endocrine therapy, etc.Recurrence and survival statusare acquired through telephone follow up, follow-up database of our own, and medical records.We use SPSS 22.0for statistical analysis.Analyze the interaction of indicators before NAC and pCR through%2 test and single sample t test; factors that have univariate correlation are included to execute binary Logistic regression analysis.Use Kaplan-Meier method and Log-rank test to analyze the prognostic value of pCR and difference between NAC and non-NAC groups on survival in different clinical stages.Results:1. Characteristics of patientsWe select 638 breast cancer patients from female breast cancer patients that are treated in the Second Hospital of Shandong University from 2004.5 to 2014.1, who are primary diagnosed and have no distant metastasis, and 140 (21.94%) of whom accept NAC,498 (78.06%) did not accept neoadjuvant chemotherapy.2. Analysis of factors affecting pCR2.1 univariate analysisCompared with non-pCR group, pCR group has shorter nursing time (t=-3.447, P=0.001); smaller tumor(t=-2.509, p=0.013), and higher proportion of diameter of tumor≤3cm (x2=9.840, p=0.002) higher weight or BMI (weight:t=2.822,p=0.006; BMI:t=2.772, p=0.007), and higher proportion of weight>60kg or BMI>25 (weight: X2=5.563,p=0.018; BMI:x2=5.280, p=0.022); longer period of chemotherapy (t=3.762,p=0.000). Age,height,propotion of nursing status, menopause, breast benign or malignant disease history,hypertension history, diabetes history, clinical stages are of no difference between pCR and non-pCR groups (p>0.05)Compared with non-pCR group, pCR group have higher proportion of ER negative status (62.5% vs22.6%, χ2=15.194, p=0.000), higher PR negative status (70.8% vs41.7%, χ2=6.751,p=0.013), higher HER2 positive status(47.4%vs19.0%, χ2=6.762,p=0.009). Histological stages, Ki-67 are of no statistical difference between the two groups. As to subtype analysis, HER2 overexpression subtype and triple negative subtype have higher pCR rates than luminal subtype (p<0.05), but HER2 overexpression subtype and triple negative subtype have no difference on pCR rate (x2=0.395,p=0.440)2.2 Multivariate analysisER(OR=0.047,95%CI:0.008-0.283) and Weight (OR=1.143,95%CI: 1.026-1.273) can be dependent predictive indicators of pCR through binary Logistic regression analysis.3. Analysis of survival of NAC patientsIn NAC group, there is no difference on DFS & OS between pCR group and non-pCR group (x2=0.138, p=0.711),although there is no death case in pCR group.There is no difference on DFS or OS between pCR group and non-NAC group (DFS:χ2=1.896, p=0.169; OS:χ2=0.572, p=0.449), but non-pCR group is worse than non-NAC group on survival (DFS:x2=8.359, p=0.004; OS:χ2=12.579, p=0.000). In phase Ⅱ and Ⅲ patients, there is no survival difference between NAC group and non-NAC group (Phase Ⅱ DFS:x2=0.266, p=0.606; OS:x2=0.098, p=0.754; Phase Ⅲ DFS:x2=0.100, p=0.152; OS:χ2=2.494,p=0.114). There is no difference on survival between patients accepting breast conserving surgery (BCS) after chemotherapy and patients accepting chemotherapy after BCS、patients not accepting BCS after chemotherapy (NAC+BCS vs Non-NAC+BCS DFS: χ2=0.097,p=0.756; OS:x2=0.077,χ2=0.781 NAC+BCS vs NAC+Non-BCS DFS: χ2=0.571,p=0.450; OS:x2=0.629, p=0.428)。Conclusion:1. In NAC breast cancer patients, patients who have high weight or BMI, short nursing time, smaller clinical tumor, ER(-), PR(-), HER2 positive have higher pCR rate. ER status and weight is the dependent predictive factors of pCR.2. Different clinical stages have no different pCR rate, HER2 overexpression subtype and triple negative subtype have better response to NAC than luminal subtype, but there is no statistical difference on pCR rate between these two subtupes.3. Patients achieving pCR have better prognosis, but there is no statistical difference between pCR group and non-pCR group; There is no survival difference between NAC patients and non-NAC patients among phase Ⅱ、Ⅲ breast cancer patients. The increasing risk on recurrence and survival do not happen in patients accepting BCS afer NAC.