| Objective:1.To investigate the effect of neoadjuvant therapy,relapse and metastasis on the molecular typing of invasive breast cancer.2.To analysis the common types of patients with pathological complete remission after NAT.Method:Screening of 629 hospitalized cases from June 2015 to December 2017 in the Fourth Hospital of Hebei Medical University.Patients were female,aged 23-82.Among them,327 cases were ? 50 years old and 302 cases were >50 years old.Invasive ductal carcinoma had 553 cases.Invasive lobular carcinoma had 31 cases.Mucous adenocarcinoma had 18 cases.Medullary carcinoma had 11 cases.Invasive ductal lobular mixed carcinoma had 9 cases.Invasive ductal carcinoma with micro papillary carcinoma had 7cases.There were 220 cases of negative lymph nodes and 409 cases of positive lymph nodes.The maximum tumor size was less than or equal to 2cm in 214 cases,2-5cm in 365 cases,and >5cm in 50 cases.These patients came from four separated groups.The first group included 432 cases of breast cancer that received neoadjuvant therapy before surgery and did not achieve pCR.The second group collected 81 cases of lymph node metastasis after chemotherapy after breast cancer resection.The third group collected 61 cases of distant metastasis lesions after chemotherapy after breast cancer resection.There were 32 cases of liver metastases,21 cases of lung metastases,6 cases of bone metastases,and 2 cases of brain metastases.The fourth group included 55 cases of breast cancer that received neoadjuvant therapy before surgery and achieved pCR.Immunohistochemistry was used to detect the expression of ER,PR,HER2 and Ki-67 in each group.The results of HER2 immunohistochemistry for 2+ all required fluorescence in situ hybridizationfor the final expression.And we based on these indicators to determine the molecular classification of breast cancer.The SPSS 22.0 statistical software was used to analyze the changes.P<0.05 was considered statistically significant.Results:1.Changes of ER,PR,HER2,Ki-67 and molecular typing before and after NATIn pre-and post-neoadjuvant chemotherapy,the change of ER,PR,HER2 from negative to positive expression were 19 cases,31 cases,and 8 cases,respectively.From positive to negative expression were 34 cases,54 cases,9cases respectively.Ki-67 changed from low to high expression in 11 cases,from high to low expression in 133 cases.The number of cases from Luminal type B HER2 negative to Luminal type A were 53.The other changes were minor.The overall rate of change from positive to negative or from negative to positive expression for ER before and after NAT was 12.27%(53/432).HER2 was 3.94%(17/432).The differences were not statistically significant(P>0.05).The overall rate of change of PR was 19.68%(85/432).The difference was statistically significant(P=0.017).The overall rate of change of Ki-67 was 33.33%(144/432).The difference was statistically significant(P<0.001).When further dividing Ki-67 expression into three groups,that was,<14% was a group,14%-30% was a group,and >30% was a group,the difference was statistically significant(P < 0.001).When the analysis was performed for cases in which the ER change before and after NAT exceeded20% or the change in PR exceeded 20% or the change in Ki-67 exceeded 10%,the differences were not statistically significant(P>0.05).The changes of Luminal A and Luminal B HER2 negative expression before and after NAT were statistically significant(P<0.001).However,there was no statistically significant difference in Luminal B type HER2 positive,HER2over-expression,and Basal-like type(P=0.236).The overall rate of change of molecular typing was 37.50%(162/432).The difference was statistically significant(P<0.001).2.Changes of ER,PR,HER2,Ki-67 and molecular typing between primary tumor and metastases lymph nodeBetween primary tumor and metastases lymph node,the change of ER,PR,HER2 from negative to positive expression were 4 cases,7 cases,and 5cases,respectively.From positive to negative expression were 10 cases,9cases,5 cases respectively.Ki-67 changed from low to high expression in 5cases,from high to low expression in 5 cases.The number of cases from Luminal type B HER2 positive to HER2 positive was 5.The other changes were minor.The overall rate of change of ER,PR,HER2,Ki-67,and molecular typing between primary tumor and metastasis lymph node were17.28%(14/81),19.75%(16/81),and 12.35%(10/81),12.35%(10/81),29.63%(24/81)respectively and the differences were not statistically significant(P> 0.05).When further dividing Ki-67 expression into three groups,the difference was not statistically significant(P=0.998).When the analysis was performed for cases in which the ER change exceeded 20% or the change in PR exceeded 20% or the change in Ki-67 exceeded 10%,the differences were not statistically significant(P>0.05).3.Changes of ER,PR,HER2,Ki-67 and molecular typing between primary tumor and distant metastasesBetween primary tumor and distant metastases,the change of ER,PR,HER2 from negative to positive expression were 6 cases,7 cases,and 2 cases,respectively.From positive to negative expression were 3 cases,8 cases,4cases respectively.Ki-67 changed from low to high expression in 14 cases,from high to low expression in 4 cases.The number of cases from Luminal type A to Luminal type B HER2 negative was 6.The other changes were minor.The overall rate of change of ER,PR,HER2,Ki-67,and molecular typing between primary tumor and distant metastases were 14.75%(9/61),24.59%(15/61),9.83%(6/61),34.43%(21/61),and there were no significant differences(P>0.05).The overall rate of change of Ki-67 was 29.51%(18/61).The difference was statistically significant(P = 0.031).When further dividing Ki-67 expression into three groups,the difference was statistically significant(P=0.007).When the analysis was performed for cases in which the ER change exceeded 20%,the difference was statistically significant(P =0.048).When the analysis was performed for cases in which the PR change exceeded20% or the change in Ki-67 exceeded 10%,the differences were not statistically significant(P>0.05).4.Pathological features of patients with pCR after neoadjuvant therapyThe pCR rate of Luminal B HER2 positive,HER2 overexpression and Basal-like typing patients was higher than Luminal A and Luminal B HER2 negative typing.The difference was statistically significant(P=0.004).The expression of ER and PR were negatively correlated with pCR(P<0.05).The expression of Ki-67 was positively correlated with p CR(P=0.001).Conclusion:1.There were significant changes in the expression of PR,Ki-67,and molecular typing before and after NAT.The expression of Ki-67 decreased after NAT.The change of molecular typing expression was mainly Luminal B type HER2 negative became into Luminal A type.NAT had no significant effect on the expression of ER and HER2.After NAT,the patient's molecular classification should be re-determined and the treatment plan should be adjusted in time.2.No significant changes in the expression of ER,PR,HER2,Ki-67,and molecular typing between primary tumors and lymph node metastases were performed.But there were still some cases that had changed.3.The change of Ki-67 expression was mainly the low expression of Ki-67 in primary tumors became into high expression in distant metastases.ER was more variable between primary tumors and distant metastases.It was recommended to detect the expression of Ki-67 and ER in distant metastasis to guide the rational use of drugs in the clinic.4.Patients with Luminal B HER2 positive,HER2 overexpression,and Basal-like typing were more likely to achieve pCR.Patients whose ER or PR were negative or Ki-67 was high were more likely to achieve pCR.Neoadjuvant therapy was more effective. |
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