Clinicopathological Features Of Breast Cancer With Low HER2 Expressionand Analysis Of Factors Related To The Efficacy Of Neoadjuvant Chemotherapy

Background : Human epidermal growth factor receptor 2(HER2)targeting drugs are mainly targeted at HER2-positive breast cancer,and are not recommended for breast cancer with low HER2 expression(HER2immunohistochemistry was 1+ or 2+ with negative in situ hybridization).However,breast cancer with low HER2 expression has different levels of HER2 protein expression,which has potential therapeutic needs.New targeted drugs to optimize the payload and connection,has high drug-loading ratio,improved the traditional positive HER2 breast cancer prognosis,at the same time,the study found that its role through effective across a cell membrane so that the "bystander effect",and can show activity in breast cancer HER2 lower expression,opens up a new situation about low HER2 expression of breast cancer treatment research.Low expression of HER2 may become a new type of breast cancer and usher in more accurate treatment.However,there are still few studies on the treatment of patients with low expression of HER2 in breast cancer,and there is a lack of standard treatment regimens and little understanding of its clinicopathological features.A better understanding of the clinicopathological features of breast cancer with low expression of HER2 is conducive to the study of its treatment.Objective:Clinicopathological data of patients with HER2-negative breast cancer who underwent initial neoadjuvant chemotherapy were collected to compare the differences in different levels of HER2 protein expressions(IHC0,IHC1+,IHC2+/ISH-)and analyze the factors related to the efficacy of neoadjuvant chemotherapy for breast cancer with low HER2 expression,aiming to better understand the breast cancer with low HER2 expression.Methods:Retrospective analysis was used to collect clinicopathological data of 161 patients with HER2-negative breast cancer who received initial treatment with neoadjuvant chemotherapy from March 2019 to March 2021 in the Department of Breast Surgery,Affiliated Hospital of Southwest Medical University.Including age,menstrual status,tumor size(T stage),axillary lymph node status,TNM stage,histological grade,molecular typing,Estrogen receptor(ER),Progesterone receptor,PR),human epidermal growth factor receptor 2(HER2),nuclear proliferation index(Ki-67),Pathological complete response(p CR)and other indicators,and analysis of variance was used for counting data,chi-square test and rank-sum test for measuring data.The differences of various clinicopathological indicators in different levels of HER2 protein expression(IHC0,1+,2+/ISH-)were compared.Univariate and multivariate binary Logistic regression was used to analyze the factors influencing the pathological complete response(p CR)rate of breast cancer patients with low HER2 expression after neoadjuvant chemotherapy,and P < 0.05 was considered as statistically significant difference.included in this study,including 108 cases of HER2-low expression breast cancer,accounting for 67.1% of HER2-negative breast cancer.HER2 IHC0,IHC1+,IHC2+/ISH-showed no statistical difference in age,menstrual status,T stage,TNM stage and Ki-67 expression(P > 0.05).There were statistically significant differences in axillary lymph node metastasis status,histological grade,molecular typing,estrogen receptor expression and progesterone receptor expression(P<0.05).HER2 IHC1+ and IHC2+/ISH-patients with breast cancer compared with HER2 Patients with IHC0 breast cancer had higher rates of axillary lymph node metastasis(P=0.048),lower histological grade(P=0.006),more hormone receptor expression(P<0.001),and more Luminal type breast cancer(P<0.001).Pathological complete response(p CR)after neoadjuvant chemotherapy showed no statistical difference in HER2 IHC0,1+,2+/ISH-(P=0.099).The p CR rate of HER2 low expression(IHC1+,2+/ISH-)in HER2-negative population and Luminal subgroup was lower than that of HER2 IHC0,and the difference was statistically significant(P< 0.05),but there was no statistical difference in TNBC subgroup(P=0.814).Univariate analysis of 108 cases of breast cancer patients with low HER2 expression showed that axillary lymph node status and estrogen receptor status were the influencing factors of p CR rate of neoadjuvant chemotherapy for breast cancer with low HER2 expression(P<0.05).After controlling confounding factors by multivariate analysis,axillary lymph node status showed no statistical difference(P>0.05).Age,histological grade and estrogen receptor status were independent factors influencing the p CR rate of neoadjuvant chemotherapy forResults:A total of 161 patients with HER2-negative breast cancer were breast cancer with low HER2 expression(P< 0.05).Conclusion:Different levels of HER2 protein expression(IHC0,IHC1+,IHC2+/ISH-)in patients with HER2-negative breast cancer have unique clinicopathological characteristics.Low expression of HER2 cannot be equal to HER2 IHC0,and low expression of HER2 accounts for a large proportion in traditional HER2-negative breast cancer.In the era of precision therapy,Breast cancer patients with low HER2 expression have great potential for more individualized treatment;In the HER2-negative population and the Luminal subgroup,the pathological complete response rate of breast cancer with low HER2 expression after neoadjuvant chemotherapy was lower than that of patients with zero HER2 expression.Age,histological grade and estrogen receptor status were independent influencing factors of the pathological complete response rate of breast cancer with low HER2 expression after neoadjuvant chemotherapy.