IHC Marker Regulation Effects And Survival Study On Breast Cancer Patients Treated By Neoadjuvant Chemotherapy

PURPOSE:To study the changes and respective clinical significance of IHC markers expression in breast cancer patients’ specimen pre- and post anthracycline and paclitaxel contained neoadjuvant chemotherapy.MEHODS:A retrospective analysis was introduced on 139 female patients treated with hospitalized neoadjuvant chemotherapy contained anthracycline and paclitaxel agents from January 2008 to August 2014 in hospital. Associated clinical test results were collected; Age, family history, size of primary lesion, positive number of metastatic lymph node, changes of IHC markers(ER, PR, HER2, Ki-67, p53) after neoadjuvant chemotherapy, regime and the cycle counts of neoadjuvant chemotherapy, the following therapies after surgery, the recurrence and survival statistics. Chemotherapy efficiency and recurrence were evaluated by RESIST criterion; The histological results were classified by Luminal standard. The statistical software SPSS 19.0 was introduced in index analysis:1) Significance of biomarkers’ changes were analyzed by pair tests(Chi-square Test and t Test); 2) Relevance of therapy efficiency(pCR) and factors such as biomarker changes were testified by single-factor analysis; 3) The differences of DFS between subgroups were analyzed by Kaplan-meire curve.RESULTS:There were 139 patients involved,5 death in 37 recurrence, the median period of follow-up is 47.5 mo. The number of biomarker switches and changes post-surgery:37 in PR(30.08%, P<0.001),30 in PR(24.39%, P<0.001),43 in HER2(34.96%, P<0.001),68 down-regulates more than 5 percent in Ki-67(55.28%, P<0.001),41 in p53(33.33%, P<0.001); Histological grades(P=0.013) and counts of pre-surgery chemotherapy cycles(P=0.002) were statistically related to pCR outcomes. There was no significant difference between pCR patients and non-pCR patients on DFS(P=0.126); Family history of breast or gynaecological cancer(P=0.003), more than 4 positive axillary lymphonodes(P=0.007), poor differentiation(P=0.004) were proven to be risk factors of recurrence. Patients who experienced more than 5 percent down-regulations of Ki-67(P=0.015) or received radiotherapy post-surgery(P=0.029) had longer DFS, while patients whose ER(P=0.001) or PR(P=0.029) switched to negative, p53 mutation (P=0.003) or HER2 (P=0.106, obviously but not significantly different) switched to positive suffered worse DFS.CONCLUSIONS:There are significant changes of IHC biomarkers expression in breast cancer after neoadjuvant chemotherapy, and such changes have clinical senses: both negative-oriented switching of ER or PR and positive-oriented switching of p53 indicates bad prognosis. Positive-oriented switching of HER2 is a potential risk factor of recurrence though the effects on DFS is not statically significant. While more than 5 percent down regulation of Ki-67 is a signal to better prognosis. Bringing with longer DFS, post-surgery regional radiotherapy keeps down the recurrence both locally and systemically. Patients with poor differentiation and more therapy cycles are more feasible to pCR achievement. As to HR positive patients, pCR should not be set as the optimal and terminal goal in neoadjuvant chemotherapy. Excessive therapy cycles to hormone-receptor positive patients aim to better remissions should be avoided for adverse effects and drug resistance.