Correlation Between Plasma Fibrinogen Level And Neoadjuvant Chemotherapy Effect And Prognosis In Breast Cancer

Background and PurposeBreast cancer is the most common female malignant tumor in the world.It is characteristic of high heterogeneity,high incidence,and low 5-year survival rate,especially in locally advanced or metastatic breast cancer patients,which poses a serious threat to women's life and health.As a standard treatment for patients with locally advanced breast cancer,neoadjuvant chemotherapy has been confirmed effective in a number of studies,which can not only reduce the clinical stage of breast cancer,improve the operation rate,but also improve the breast-conserving rate of patients with locally advanced breast cancer without reducing survival.However,the pathologic complete response?pCR?of neoadjuvant chemotherapy is still low,about20%-30%.In addition,clinically effective biomarkers predictive of pCR and survival are lacking in such patients.A number of studies have confirmed that fibrinogen plays an important role in angiogenesis,blood metastasis,matrix formation,and tumor invasion of malignant tumors.Clinically,elevated levels of plasma fibrinogen have been shown to be associated with progression and adverse outcomes in malignancies.Higher preoperative plasma fibrinogen level has been shown to be associated with breast cancer development and prognosis.However,few studies are available to examine the correlation between the dynamic change of plasma fibrinogen level and neoadjuvant chemotherapy.The aim of this study was to investigate the correlation between the post-chemotherapy change of fibrinogen level and the treatment effect of neoadjuvant chemotherapy and patient prognosis in breast cancer.Materials and MethodsTwo hundred breast cancer patients were enrolled in this study.All the patients received preoperative neoadjuvant chemotherapy in the breast surgery department of Henan Cancer Hospital,Zhengzhou University from October 30,2013 to October 30,2015.The plasma fibrinogen levels before initial neoadjuvant chemotherapy and after the end of neoadjuvant chemotherapy were reviewed retrospectively.Fibrinogen level was defined as normal?2.0-4.0 g/L?,higher?>4.0 g/L?,or lower?<2.0 g/L?.The histological classification of breast cancer was based on the 2003 edition of the WHO Classification of Tumors of the Breast.Tumor-Node-Metastasis?TNM?staging was determined according to the International Union Against Cancer?UICC?NTM classification.Molecular typing was based on the 2011 St.Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer.The inclusion criteria were:pathological examination confirmed invasive ductal carcinoma,patients with locally advanced breast cancer from IIb/IIIc,female breast cancer;measurable primary tumor,no distant metastases,did not receive malignant tumor related radiotherapy,chemotherapy,or immunotherapy,initial diagnosis of breast cancer,and complete medical record data and follow-up information.The exclusion criteria were:combined with other malignancies,male breast cancer,other pathological types of breast cancer,patient who could not tolerate chemotherapy,or discontinued treatment during chemotherapy,involved in other clinical studies,pregnant or lactating women.The patients were treated strictly in accordance with the 2013 Breast Cancer Treatment Guidelines.The follow-up deadline is December 30,2018.Disease-free survival?DFS?was defined as the time from initial chemotherapy to the date of first recurrence or metastasis in the axilla,breast,or supraclavicular lymph nodes,or to the date of last follow-up.Overall survival?OS?was defined as the time from initial chemotherapy to the date of death due to any cause or to the date of last follow-up.Fisher's exact probability method and Chi-square test were used to analyze the relationship between plasma fibrinogen level before chemotherapy and the clinical characteristics of breast cancer;and the correlation between the change of fibrinogen level and pathological complete response?pCR?.Logistic regression analysis was used to observe the independent predictors of pCR.Kaplan-Meier analysis,log-rank analysis,and Cox regression model were used to analyze the correlation between the post-chemotherapy change of fibrinogen level and patient outcomes?DFS,OS?,and explore the potential predictors.Results1.Of the 200 patients enrolled,90?45.0%?were found with lower plasma fibrinogen level,and 110?55.0%?with normal or elevated fibrinogen level before chemotherapy.Plasma fibrinogen level before chemotherapy was associated with menstrual status,recurrence rate,lymph node state?p<0.05?.The patients with lower fibrinogen level before neoadjuvant chemotherapy were associated higher proportion of menopause and lower lymph node metastasis rate.2.Neoadjuvant chemotherapy resulted in pCR in 45?22.5%?of the 200 patients.Targeted therapy,molecular typing,tumor size,and post-chemotherapy change of fibrinogen level were associated significantly with pCR?p<0.05?.HER2-positive patients receiving targeted therapy,triple-negative,T_1-2 breast cancer,and the patients with reduced fibrinogen level after chemotherapy were more likely to achieve pCR.Multivariate regression analysis showed that targeted therapy?95%CI:2.367-9.647?,molecular typing?triple-negative versus Luminal A,95%CI:1.249-8.514?,tumor size?95%CI:1.056-6.678?,and post-chemotherapy change of fibrinogen level?95%CI:0.097-3.641?were independent predictors of pCR?p<0.05?.3.The follow-up period was 36-60?46.1 on average?months.A total of 8patients were lost to follow-up.The follow-up was valid in 96.0%of the 200 patients.Kaplan-Meier method and log-rank test showed statistically significant difference in DFS rate between the patients with elevated fibrinogen level after chemotherapy and those with reduced fibrinogen level after chemotherapy?p=0.033?,but no significant difference in OS rate between the two groups?p=0.159?.4.Cox proportional hazard model for analysis of prognostic factors showed that molecular typing?95%CI:1.551-6.747?,lymph node status?95%CI:1.528-6.947?,and post-chemotherapy change of fibrinogen level?95%CI:1.058-4.217?were the independent prognostic factors of DFS in breast cancer patients receiving neoadjuvant chemotherapy?p<0.05?.The patients with triple-negative,N2-3 breast cancer,and elevated post-chemotherapy fibrinogen level had shorter DFS.Molecular typing?95%CI:1.235-4.671?and lymph node status?95%CI:1.641-6.947?were independent prognostic factors of OS for breast cancer patients receiving neoadjuvant chemotherapy?p<0.05?.The patients with triple-negative,N_2-3 breast cancer receiving neoadjuvant chemotherapy were associated with shorter OS.Conclusions1.The breast cancer patients with lower fibrinogen level before neoadjuvant chemotherapy were associated with higher proportion of menopause and lower lymph node metastasis rate.2.The change of fibrinogen level after neoadjuvant chemotherapy is associated with the treatment effect.The patients with reduced post-chemotherapy fibrinogen level were more likely to achieve pCR.3.The change of fibrinogen level after neoadjuvant chemotherapy is associated with the prognosis.The patients with reduced fibrinogen level after neoadjuvant chemotherapy were associated with longer DFS.