Clinicopathological Characteristics Of De Novo Stage Ⅳ Breast Cancer And The Optimization Of Its Locoregional Treatment Strategies

Background: The clinicopathological features,metastasis characteristics and subsequent treatments of the patients with de novo stage Ⅳ breast cancer are closely related to their prognosis.The criteria for grouping these factors related to prognosis are not uniform,and they are interrelated and change dynamically.Retrospective studies at home and abroad have not reached a consistent conclusion.In particular,there has been controversy about whether surgical treatment of primary tumors can bring survival benefits.How to make locoregional interventions for potential benefit subgroups through precise screening,and how to optimize locoregional treatment strategies on the basis of systemic treatment,so as to maximize the survival benefit of the surgical population,are problems that needs to be solved urgently.The molecular classification of breast cancer is an important supplement to the traditional histopathological classification.Both HER-2 overexpression and basal-like breast cancer can be distinguished from a clinicopathological perspective,but there is still controversy regarding the division of luminal subtypes.In view of this,we further detailed the expression of ER/PR and conducted a preliminary study on the correlation of molecular expression.Content: Part Ⅰ: To investigate the clinicopathological features of metastases and the effect of treatment on prognosis in de novo stage Ⅳ breast cancer.Part Ⅱ: To explore the differences between the surgery group and the non-surgery group and the potential benefit factors;to investigate the influence of the clinicopathological and metastatic features at the initial diagnosis and after surgery,and the treatment at the operative stage on the prognosis of patients.Part Ⅲ: To study the correlation between the expression of different molecular markers,the factors affecting the correlation,and the relationship between the correlation and its influence on the prognosis.Methods: Clinical data of 518 patients with de novo stage Ⅳ breast cancer admitted to the Affiliated Cancer Hospital of Tianjin Medical University from February 2007 to December 2017 were collected and analyzed retrospectively.Follow-up was initiated at the time of diagnosis of de novo stage Ⅳ breast cancer and ended at the time of death or December 31,2020.Firstly,age,main complaint time,first clinical T/N stage,metastasis characteristics,molecular marker expression and treatment were included,and the prognostic factors of all patients,339 ER-positive and 179 ER-negative patients were investigated.Secondly,the differences between the surgical group and the non-surgical group were analyzed by Fisher’s exact test,and the potential survival benefit factors of the surgical group were analyzed.The relevant indexes obtained by postoperative pathology and the treatment at the surgical stage were included to analyze the prognostic factors of 266 surgical patients.Log-Rank test was used for univariate analysis of prognosis,and Cox regression model was used for multivariate analysis of prognosis.Finally,according to the difference between ER and PR expression rate and HER-2 semi-quantitative,the equivalent value replacement was performed,and the other molecular markers were replaced by the binary value of 0 and 1 according to the corresponding cut-off value,and the Pwcorr test was used for bivariate correlation analysis.Stata 15.0 software was used for statistical analysis,and P<0.05 was considered statistically significant.Results: 1.Clinical T and N stage,metastasis characteristics(P<0.001),ER/PR expression,Ki-67 status,chemotherapy at the initial diagnosis stage,primary tumor surgery(P=0.004)and radiotherapy were correlated with prognosis.The clinical N stage,metastasis characteristics(P=0.001),PR expression,Ki-67 status,primary tumor surgery(P=0.019)and radiotherapy were related to the prognosis of ER-positive patients at the first diagnosis.The clinical T stage,metastasis characteristics(P<0.001),whether to undergo chemotherapy at the initial diagnosis stage and at the follow-up of the disease progression,and primary tumor surgery(P=0.021)were related to the prognosis of ER-negative patients.2.Patients in the surgical group have potential survival benefits in terms of clinical T and N stage,first-diagnosis metastasis characteristics,first-diagnosis chemotherapy,and primary tumor radiotherapy.First diagnosis metastasis characteristics(P<0.001),postoperative Ki-67 status(P=0.002),postoperative pathological T stage(P=0.009),postoperative pathological N stage(P<0.001)and postoperative primary focus area radiotherapy(P<0.001)were independent prognostic factors for surgical patients.3.There were positive correlations between ER and PR(P<0.001),HER-2 and Ki-67 (P<0.001),HER-2 and P53(P=0.027),Ki-67 and P53(P<0.001)in 269 patients with ER(+)before chemotherapy,but negative correlations between ER and HER-2 (P<0.001),ER and Ki-67(P=0.004),ER and P53(P=0.013),PR and HER-2(P<0.001),PR and Ki-67(P=0.001).In 115 patients with ER(+)after chemotherapy,there was a positive correlation between ER and PR(P<0.001),between HER-2 and Ki-67(P=0.011),and between Ki-67 and P53(P=0.003),while a negative correlation between PR and HER-2(P=0.032).Conclusions: 1.The independent prognostic factors for survival of de novo stage Ⅳ breast cancer patients were not consistent in the total cohort and the ER(+/-) subgroups.The first-diagnosed metastasis and primary tumor surgery were common independent prognostic factors among them.2.First-diagnosed oligometastasis and the stable ER status in de novo stage Ⅳ breast cancer patients were the prerequisites for locoregional treatment optimization strategies.ER-positive surgical population focuses on clinical N stage,PR expression and Ki-67 status,and patients with low N stage during surgery,low Ki-67 expression status and postoperative primary focal area radiotherapy are more beneficial for survival;ER-negative surgical population focuses on clinical T stage,and patients with low T stage during operation and adequately standardized chemotherapy can have better survival benefits.3.ER positive was the basis for the correlation of the expression of molecular markers,and the correlation disappears or weakens after continuous cycles of chemotherapy.The influence of different molecular markers on the prognosis of patients in each group was related to the strength of the correlation with HER-2 expression.