The Clinical Significance Of Postoperative Wound Drainage From Breast Cancer Patients And Its Effect On Breast Cancer Cells

ObjectiveSeroma formation is one of the most common complications after breast cancer surgery.We sought to investigate the potential risk factors for Chinese breast cancer patients and explore effective methods for further prediction and prevention.Clinical investigations suggest that the removal of primary tumor in breast cancer patients may hasten the metastatic development and favorably modify the disease natural history. Postoperative drainage,a surgery-derived discharge after breast cancer operation, reflecting some biological response of the host to surgical stimulation,was assessed and explored its relationship with disease recurrence and death in our study.From in vivo study,we investigated the stimulated effect of wound drainage on breast cancer cells in term of proliferation,motility and invasion,as well as the expression of several mRNA and proteins related to tumor invasion and metastasis.MethodsPartⅠ:A prospective study of 158 female breast cancer patients undergoing surgery was performed in Cancer Hospital of Fudan Unversity,Shanghai,China. Univariate analyses were performed by chi-square test or Student's t test or Mann-Whitney test according to different data category and multivariate analyses by logistic regression.PartⅡ:A total of 1439 women undergoing surgery between Jan 1,2000 and Dec 31,2002 in Cancer Hospital of Fudan University,Shanghai,China were retrospectively studied.Survival curves were performed with Kaplan-Meier method and the predictive value of postsurgical drainage was estimated using proportional Cox regression model. PartⅢ:Breast cancer cells were treated with individual and a pooled wound fluid which were collected from five premenpausal breast cancer patients in 24h after surgery.The effect of the proliferation of MDA-MB 231,MDA-MB-231 HM, SK-BR3 and T47D were detected by WST.Meanwhiles,the motion and invasion activity were investigated by scratching and transwell test.The expression of mRNA levels was examined by RT-PCR and Western blot were applied to detect the expression of uPAR,ER and E-cadherin in cancer cell with preteated with wound drainage.ResultsPartⅠ:We observed that age(OR=1.090,95%CI 1.028-1.155,P=0.004),total serum protein concentration(OR=0.886,95%CI 0.791-0.992,P=0.036),the drainage volume on postoperative day 3(POD3)(OR=1.013,95%CI 1.002-1.023,P=0.017) and time to daily drainage volume not more than 30ml(TTV30;OR=1.273,95%CI 1.039-1.561,P=0.020) were independent risk factors for seroma formation. Additionally,significant difference in daily drainage volume was substantiated in the analysis by seroma formation(P=0.034) rather than by type of surgery(P=0.713).PartⅡ:Drainage volume of postoperative day 1(POD1) was positively associated with tumor size(P＜0.001) and ALNs involvement(P=0.030).In addition,its level was inversely,but weakly correlated with serum protein concentrations(r_s=-0.058, P=0.028).In univariate survival analysis,tumor size(P=0.001 and P=0.005, respectively),ALNs status(both P＜0.001),tumor subgroup(P=0.009 and P=0.019, respectively) and drainage volume of POD1(both P=0.006) were significantly associated with patients' recurrence-free(RFS) and overall survival(OS).In the multivariate Cox proportional regression as well,in addition to ALNs status(P＜0.001; HR=4.851 and P＜0.001;HR=5.808,respectively),tumor subgroups(P=0.006; HR=1.540 and P=0.020;HR=1.723,respectively) and serum albumin concentrations (P=0.036;HR=0.719 and P=0.025;HR=0.589,respectively),drainage volume of POD1(P=0.035;HR=1.412;95%CI 1.025-1.944 and P=0.047;HR=1.667;95%CI 1.007-2.758,respectively) showed to be an independent predictor of poor recurrence-free survival and overall survival.When it come to the recurrence and mortality hazard rate,patients with high drainage volume of POD1 showed an earlier major surge peaking and dominantly above the low group during all the follow-up periods. PartⅢ:1%wound fluid could significantly stimulate the proliferation of MDA-MB 231,MDA-MB-231 HM and SK-BR3,but no effect to T47D.Meanwhiles, wound fluid cound enhance the migratory and invasive abilities of MDA-MB-231. When the SK-BR3 cell were treated with 2.5%wound fluid for 48 hours,the expression of VEGFC mRNA was increased while the PAI-1 mRNA level decreased. The wound fluid could down regulate the expression of E-cadherin and up regulate the expression of uPAR.ConclusionAge,total serum protein concentration,the drainage volume on POD3 and time to TTV30 were independent risk factors for seroma formation.Although the pathogenesis of seroma remains controversial,such risk factors should be considered for prediction and prevention of seroma formation in Chinese breast cancer patients.In addition to tumor size,ALNs status and serum albumin concentrations,the results showed that drainage volume of POD1 was independently indicative of prognosis for patients with breast cancer.This implies that wound drainage,reflecting the profile of surgical stimulation,was related with the natural course of breast cancer progression. Awareness of the relationship between early surgery stimulated effects and wound healing response might help to explore new strategies to block or deplete these harmful effects,and improve patients' outcome finally.From the experiment,we found that wound drainage from breast cancer patients could significantly stimulated the breast cancer cells proliferation,migration and invasion.It may exert its stimulation effect through regulating the expression of mRNA and proteins related to tumor invasion and metastasis.