Correlation Between Tertiary Lymphoid Structure And Prognosis Of Breast Cancer

Background:Breast cancer is a common malignant tumor of the breast,often leading to the death of patients.Breast cancer is a heterogeneous disease,and there are huge differences in clinical manifestations and survival rates among different subtypes of breast cancer.Tertiary lymphoid structure(TLS)refers to the ectopic lymphoid structure that is commonly found in inflammatory or tumor tissues and is similar to the secondary lymphoid structure,which has guiding significance for the prognosis of breast cancer.Objective:TLS has become an important prognostic indicator in many primary tumors.We aimed to investigate the expression level of TLS in breast cancer and its prognostic significance.Methods:A total of 107 patients who were pathologically diagnosed with breast cancer and treated at the Department of Breast Surgery,Shengjing Hospital of China Medical University from January 2005 to December 2019 were enrolled.Patients were followed up for a long time and their paraffin-embedded tissues were collected for sectioning.Hematoxylin and eosin(H&E)staining and Immunohistochemistry(IHC)staining were used to process the paraffin-embedded sections of breast cancer specimens.TLS was defined as clustered lymphocyte clusters in HE sections and positive expression of CD3 and CD20 in immunohistochemical sections.Breast cancer TLS were classified into five levels based on the location and number of TLS.Level 0:No TLS exists in the slice.Grade 1:no TLS within the cancer tissue and 1-4 TLS present outside the cancer tissue.Grade 2:no TLS within the cancer tissue and more than four TLS outside the cancer tissue.Grade 3:the presence of 1-4 TLS within the cancer tissue,regardless of the number of TLS present outside the cancer tissue.Grade4:more than 4 TLS within the cancer tissue,regardless of how many TLS exist outside the cancer tissue.Through prognostic follow-up and electronic medical records,patients who were diagnosed with breast cancer recurrence or metastasis at the last examination and died were defined as dying of breast cancer Distant metastasis refers to the metastasis of primary breast cancer to organs such as liver,lung,bone and other organs,excluding chest wall or axillary lymph node metastasis.The Kaplan-Meier method was used to plot the survival curve of the patients,and Pearsonχ2 test or Fisher exact test was used to evaluate the correlation between clinicopathological features and TLS status when appropriate.Binary logistic regression analysis was used to evaluate the relationship between distant metastasis of breast cancer and TLS.Results:1.A total of 107 breast cancer patients diagnosed and treated in Shengjing Hospital of China Medical University from January 2005 to December 2019 were included in this study.The age of the patients ranged from 24 to 75 years,with a median age of 49years.All cases were invasive ductal carcinoma(107 cases).Of these 107 patients,9patients had unclear metastasis.Analysis of the remaining 98 patients showed that 40patients had distant metastasis and 58 patients did not have distant metastasis.The maximum follow-up time was 154 months,the minimum follow-up time was 15months,and the median follow-up time was 70 months.A total of 52 patients died of breast cancer..There were 22 cases of grade 0(20.6%),25 cases of grade 1(23.4%),13 cases of grade 2(12.1%),39 cases of grade 3(36.4%),and 8 cases of grade 4(7.5%).2.The TLS positive rate of breast cancer patients with tumor size<5cm~2was higher than that of breast cancer patients with tumor size>5cm~2(86.1%vs S60.7%,P=0.004).Patients with intratumoral TLS had a lower probability of lymph node metastasis than those without(33.3%vs57.4%,P=0.013).There was no significant correlation between TLS and age,height,weight,ER expression,PR expression,Ki-67 and P53 expression,breast cancer stage3.Kaplan-Meier survival analysis showed that TLS positive breast cancer patients,The Overall survival(OS)of breast cancer patients with TLS was longer than that of TLS negative patients(OS:102±6.524 months vs 61±7.076 months,P=0.011).The OS of patients without TLS(grade 0),patients with only extra-tumoral TLS(grade 1 vs.grade 2),and patients with intratumoral TLS(grade 3 vs.grade 4)were 61±7.076,89±10.517,and 107±6.723 months,respectively(P=0.008).The higher the TLS grade,the longer the OS.The OS of grade 0-4 were 61±7.076 months,87±14.986 months,89±14.856 months,102±6.816 months,154±0 months,respectively(P=0.046).4.Intratumoral TLS and endocrine therapy are independent prognostic factors for distant metastasis of breast cancer.Breast cancer patients with intratumoral TLS positive have a lower probability of distant metastasis than those with intratumoral TLS negative,and patients with endocrine therapy have a higher probability of distant metastasis than those without endocrine therapy.Conclusions:In breast cancer,TLS does exist.Compared with breast cancer patients without TLS,breast cancer patients with TLS have smaller tumor volume and longer OS.Breast cancer patients with intratumoral TLS have longer OS than those without intratumoral TLS.Intratumoral TLS and endocrine therapy are independent prognostic factors for distant metastasis of breast cancer.Breast cancer patients with intratumoral TLS have a lower probability of distant metastasis than those without intratumoral TLS,and patients with endocrine therapy have a higher probability of distant metastasis than those without endocrine therapy.Patients with intratumoral TLS positivity had a lower probability of lymph node metastasis than those with intratumoral TLS negativity...