| BackgroundBreast cancer is one of the most common malignancy and one of the leading causes of cancer-related deaths worldwide among women, and some patients are diagnosed with locally advanced breast cancer. Neoadjuvant chemotherapy (NAC) is the standard of care for locally advanced breast cancer, and it significantly facilitates breast-conserving surgery and reduces postoperative recurrence risk. It was found that the patients with the same stage or same pathologic type accepted the same new adjuvant chemotherapy scheme in clinical, but their curative effect and prognosis were different actually. With the deepening and development of the molecular biology of breast cancer research in recent years, immunohistochemical technique has been widely used, and people realize that the important cause of tumor heterogeneity attribute to the biology characteristics in breast cancer. The differences of molecular level and genetic level in patients lead to the different sensitivity to chemotherapy drugs, even if with the same tumor histologic types, but the changes in corresponding molecular genetic in patients also are not completely consistent, therefore, even if the patients accepted the same chemotherapy regimens, the curative effect and prognosis might be different.Therefore,it is important to understand the differences in breast cancer molecular level and the correlation of clinical characteristics. It has the profound significance to look for the biological or inflammatory indicators to predict the prognosis and evaluate the response to neoadjuvant chemotherapy in breast cancer patients, and it has a certain guiding significance to formulate individualized treatment for the breast cancer patients.Breast cancer is regarded as a kind of hormone-dependent tumor, its regulation differentiation and proliferation were affected by estrogen receptor (ER) and progesterone receptor (PR). ER and PR are recognized as the only predictable biomarkers of endocrine therapy efficacy. The expression of ER and PR in breast tumor tissue is closely related with its pathological features, biological behavior,endocrine therapy sensitivity, chemotherapy sensitivity and prognosis. Therefore,understanding the expression of ER and PR in breast cancer tissue is of great significance. Previous studies had shown that ER and PR expression would have different changes following NAC, however, there is a larger controversy in the alterations, such as whether the changes are related to chemotherapy regimens, and the different predictive values of the pretreatment ER and PR to NAC curative effect.Therefore, assessment of ER and PR changes post-NAC treatment is vital for evaluation of NAC efficiency and will affect the subsequent individualized treatment for breast cancer patients.Inflammation in the tumor microenvironment plays an important role in the proliferation and survival of malignant cells. Neutrophils/lymphocyte ratio (NLR) or platelet/lymphocyte ratio (PLR) in peripheral blood is a useful indicator of systemic inflammation. Proinflammatory markers, including NLR and PLR, have been demonstrated to be associated with many aspects of different malignancies. The aim of the current study was to assess the associations of NLR and PLR with estrogen receptor (ER) and progesterone receptor (PR) in locally advanced breast cancer patients and their changes after neoadjuvant chemotherapy (NAC). Whether these parameters were predictive for the response to NAC in breast cancer patients was also evaluated.Purpose1. To analyse the associations between pre-treatment NLR/PLR and pre-treatment ER/PR.2. To analyse the changes of ER, PR, NLR and PLR after neoadjuvant chemotherapy,and to evaluate the correlation between NAC-induced changes in ER/PR/NLR/PLR and different chemotherapy regimens.3. To analyse the associations between NAC-induced changes of ER/PR and NLR/PLR.4. To analyse the correlation between the expression status of pretreatment ER, PR and NAC efficacy.5. To evaluate the predictive value of pretreatment NLR and PLR for NAC response.Methods132 female patients with primary locally advanced breast cancer who were treated with either ET (epirubicin/docetaxel), TEC (docetaxel/epirubicin/cyclophosphamide),or CEF (cyclophosphamide/epirubicin/fluorouracil) as NAC before surgery were included. Breast cancer patients received at most six cycles of anthracycline-based and/or taxane-based NAC every three weeks and the regimens were as follows: ET scheme (epirubiIin: 90mg/m2, docetaxel: 75 mg/m2), TEC scheme (docetaxel: 75 mg/m2 , epirubicin: 9mg/m2, cyclophosphamide: 500 mg/m2), and CEF scheme(cyclophosphamide: 500 mg/m2, epirubicin: 90mg/m2, fluorouracil: 500 mg/m2).According to the standardized procedures and interpretation standards of immunohistochemistry detection, ER and PR were immunostained before NAC and after surgical resection. NLR and PLR were defined as the absolute neutrophil count divided by the absolute lymphocyte count and the absolute platelet count divided by the absolute lymphocyte count, respectively, and were calculated from peripheral blood cell count. Peripheral blood was obtained immediately after breast cancer diagnosis and before any treatment modality (pretreatment NLR and PLR) and was also taken after one cycle of NAC. The capacity of NLR and PLR in predicting the expression level of ER, PR and the response to NAC were analyzed using receiver operating characteristic (ROC) curve analysis. All patients undergoing NAC were routinely examined by breast ultrasound, and NAC efficacy was evaluated according to the Response Evaluation Criteria in Solid Tumors (RECIST) guideline version.NLR and PLR were calculated from peripheral blood cell count and receiver operating curve (ROC) was used to determine their optimal cut-off levels. The correlation between pre-NAC NLR/PLR and ER/PR expression was analyzed by Chi-square statistics and t test. The comparisons of the means between pre- and post-treatment NLR and PLR were shown by t test. The associations between the NAC-induced changes in ER/PR/NLR/PLR and different chemotherapy regimens,and the correlations between pre-NAC NLR/PLR and NAC efficacy were analyzed by Chi-square statistics.Results1. The status of ER and PR expression before NAC are not related to NLR/PLR before NAC.2. The level of ER-positive breast cancers before NAC was higher both in NLRlow(<2.05) group and PLRlow group (<159.01), but PR-positive proportion was only higher in the PLR1ow group (<159.01 vs. > 159.01; P=0.048). No statistical difference was found between the NLRlow group and the NLRhigh group in the expression of PR.3. Changes in ER or PR expression level or status were observed in some patients.Changes of ER expression level were observed in ET/TEC/CEF group were observed in 46.88% (15/32), 57.89% (11/19) and 43.33% (13/30) cases respectively,and it looked more obvious than the other two groups. Changes of ER expression status in ET/TEC/CEF group were observed in 15.63% (5/32), 21.05%(4/19), and 10.00% (3/30) cases respectively. The change of ER expression level and/or state was evident in TEC group. Changes of PR expression level in ET,/TEC/CEF group were observed in 37.50% (12/32), 47.37% (9/19), and 30.00% (9/30) cases respectively, and the status changes of PR expression in ET/TEC/CEF group were observed in 21.88% (7/32), 15.79% (3/19), and 16.67% (5/30) cases respectively.The change of PR expression level is obvious in the TEC group, but the change in expression state is more apparent in ET group. The differences of the changes in the ER or PR expression level or status among ET, TEC and CEF groups were no significant (p>0.05, X2 test).4. The difference of NLR value was evident in TEC scheme aft-NAC (P=0.003,P<0.05), but the difference was no any significant in ET or CEF schemes (P>0.05),however, the results were influenced by G-CSF (granulocyte colony-stimulating factor). It was observed that the differences of PLR values were significant in the above three chemotherapy regimens aft-NAC(P=0.007,0.000,0.000, respectively).5. The elevated PLR would be found in the majority aft-NAC.6. The alterations of NLR and PLR after NAC correlated with chemotherapy regimens.7. The correlations between the changes in ER/PR and NLR/PLR was no significant differences (P >0.05, X2 test).8. The status of ER and PR expression before NAC are not related to NAC response.9. The patients with low pre-treatment NLR (<1.67) or PLR (<151.27) had better responses to NAC than those with high NLR (?1.67, 67.3% vs. 47.1%, P<0.05) or PLR (?151.27, 64.0% vs. 45.1%, P<0.05).ConclusionsThis article analysed the associations between pre-treatment NLR/PLR and pre-treatment ER/PR, and evaluated the predictive value of pretreatment ER, PR, NLR and PLR for NAC response, and the study shown that:1. The status of ER and PR expression before NAC were not related to NLR/PLR before NAC, but the expression level of ER and PR were relevant to pretreatment NLR or PLR, and few similar studies have been found.2. NLR, PLR would have obvious changes after NAC in breast cancer patients, and elevated PLR was found aft-NAC. The alterations of NLR and PLR after NAC were correlated with chemotherapy regimens,and different effects were shown in different NAC scheme. To date, no similar studies have been found. Changes in ER and PR expression status or level occured following NAC in some patients,and the alterations were not related to the changes in NLR/PLR or chemotherapy regimens.3. By evaluating the correlation of pretreatment ER, PR, NLR, PLR and NAC response, the results displayed that the status of ER and PR expression before NAC were not related to NAC response, but the patients in pre-treatment NLRlow group or PLRlow group had better responses to NAC, and pretreatment NLR and PLR may be important predictive indicators for NAC response in breast cancer patients. |
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