Prognostic Value Of Tumor Infiltrating Lymphocytes And Egfr Protein Expression In Patients With Triple Negative Breast Cancer

Object:To evaluate the prognostic value of tumor-infiltrating lymphocytes(TILs)and epidermal growth factor receptor(EGFR)expression,and to determine their relationship with clinicopathological parameters of triple-negative breast cancer.Methods:The clinical data of 70 TNBC patients with complete pathological reports and clinical data who underwent surgical treatment in The Affiliated Hospital of Qingdao University from January 2010 to December 2015,including age grouping(50),menstrual status(premenopausal(including menopause),after menopause),history of ovarian cancer(with/without),surgery(local excision/full breasts removed),radiotherapy(y/n),neoadjuvant chemotherapy(yes/no)\ adjuvant chemotherapy(y/n),transfer of recurrence time(early recurrence/late recurrence/not),the last follow-up time,survival state(birth/death/loss of follow-up)and pathological data,including c T(2.0cm),c N(negative/positive),histological type,tumor grade,immunohistochemistry(ER,PR,HER-2,KI-67,EGFR,CD4,CD8)were collected.Hematoxylin-eosin staining(HE)sections were used to evaluate the proportion of tumor interstitial TILs,which were divided into high(≥40%)and low(< 40%)groups.Immunohistochemistry(IHC)was used to detect the expression of TILs subsets(CD4+T,CD8+T cells)and EGFR protein.Chi-square test was used to analyze the relationship between TILs density,subsets and EGFR protein expression and clinicopathological features.Kaplan-meier method was used to analyze survival.Univariate and multivariate Cox regression analysis were used to explore the influencing factors of prognosis in TNBC patients.SPSS 25.0 software was used for statistical analysis of the data.Results:1.The 70 TNBC patients ranged in age from 32 to 80 years,with a median age of50.5 years.There were 38 patients(54.29%)aged ≥50 years;33 patients(47.14%)were menopausal;4 patients(5.71%)had a history of breast cancer.17 patients(24.28%)had a family history of other tumors.66 patients(94.29%)received axillary lymph node dissection.Only 2 patients(2.86%)received preoperative neoadjuvant therapy;58patients(82.86%)received postoperative adjuvant chemotherapy,and 20 patients(28.57%)received postoperative adjuvant radiotherapy.Recurrence and metastasis occurred in 6cases(8.57%).41 patients(58.57%)survived well.2.TILs was interpreted according to the assessment of Tumor-infiltrating Lymphocytes(TILs)in Breast Cancer recommended by the international TILs Working Group in 2014:the high proportion group has 28 cases(40%)and the low proportion group has 42 cases(60%).The number of p T(1,2 and 3)was 42(60%),27(38.57%)and1(1.43%),respectively.PN(0-1,2-3)was 39 cases(55.71%)and 27 cases(38.57%),respectively,and Nx was excluded in 4 cases.There were 13 cases(18.57%)and 57 cases(81.43%)with histological grade II and III,respectively.There were 52 patients(74.29%)with basal-like type,15 patients(21.43%)with ductal type,and 3 patients(4.28%)with other types of histology.EGFR expression was strongly positive in 10(14.29%)of 70 TNBC patients.There were 10 cases(14.26%)in CD4/CD8≤1 group,and 60 cases(85.71%)in CD4/CD8 > 1 group.3.The median disease-free survival(DFS)was 55.5 months in the low-proportion TILs group and 97 months in the high-proportion,p=0.059;The median total survival(OS)was 69.5 months in the low proportion TILs group and 97 months in the high proportion group,P =0.084.The proportion of TILs was significantly correlated with histological type(P=0.029),and there was no significant statistical difference between TILs and other pathological markers.CD4/CD8 ratio was significantly correlated with histological grade and histological type(P=0.006 and P=0.005),and there was no significant statistical difference with other pathological markers.The median DFS and OS of CD4/CD8≤1group were 11 months,and the median DFS and OS of CD4/CD8 > 1 group were 93months(P=0.030 and P=0.013),showing statistical differences.The median DFS was71.5 months in the non-strongiy positive EGFR group and 94.5 months in the strongly positive EGFR group(P =0.502).The median OS was 78.5 months in the non-strongly positive EGFR group and 94.5 months in the high proportion group,P =0.473.EGFR non-strongly positive group,TILs<40%(n=25)median DFS and OS were 24 and 36 months,respectively,and TILs≥40%(n=35)median DFS and OS were 96 months,respectively.There were statistically significant differences in DFS(P =0.035)and OS(P=0.048)among groups with different TILs ratios.EGFR positive group,TILs<40%(n=7)median DFS and OS were 98 months,TILs≥40%(n=3)median DFS and OS were 94months(P =0.513 and P =0.882).Conclusion:There was no statistically significant difference in DFS and OS between patients with triple-negative breast cancer with different TILs proportions after treatment.The prognosis of TNBC patients with CD4/CD8 ratio > 1 was better.EGFR expression had no significant effect on postoperative OS.In TNBC patients with non-strongly positive EGFR,the higher proportion of TILs,the longer postoperative DFS and OS.