Retrospective Analysis Of The Clinical And Pathological Features Of Early-stage HER-2-Low Breast Cancer In A Single Center

Background:Human epidermal growth factor receptor 2(HER-2)is closely associated with breast cancer,and current evidence suggests that HER-2-positive phenotypes can benefit from targeted therapy.It has been noted that 60%of patients with HER-2 negative breast cancer exhibit low HER-2 expression,and the updated opinions suggest that this subgroup might have different clinical and pathological characteristics.With the development and advancement of antibody-coupled drugs,T-DXd has demonstrated antitumor activity in HER-2 low-expression cells.Meanwhile,compared with traditional conventional treatment,it also significantly improved patients’prognosis in advanced breast cancer populations.However,whether HER-2 expression status correlates with estrogen receptors and progesterone receptors and other clinical and pathological features has not yet reached a consensus.Objective:To explore the differences in clinical and pathological characteristics between early-stage HER-2 low expression(HER-2 1+and HER-2 2+/FISH-)breast cancers and HER-2 zero expression(HER-2 0)breast cancers and their specific tumor biological behavior;and to investigate whether zero HER-2 expression is associated with poor prognosis in HER-2 negative breast cancers.Methods:The subjects were obtained from the patients who underwent surgical treatment and comprehensive antitumor therapy for breast cancer at our center from 2014-2017,and a total of 1636 patients were included in this study,of whom 106 were lost at discharge,and follow-up data were obtained for a total of 1530(93.5%)patients,with a follow-up period of9 to 108 months and an average follow-up time of 66.47 months.The primary observed endpoint was the occurrence of recurrent/metastatic events of breast cancer or deaths including all types of causes,with 107 recurrent events and 66 deaths(62 deaths due to distant metastases of breast cancer)during the follow-up period.Data included age at diagnosis,menstrual status,estrogen receptor,progesterone receptor,Ki-67 values,HER-2,FISH,surgical modality,P-stage,number of lymph node metastases,and whether adjuvant therapy(chemotherapy,radiotherapy,and endocrine therapy)received.For the count data,theχ~2test was applied to explore the differences between the HER-2 low expression group and the HER-2 zero expression group in the composition ratio of the above characteristics;for the measurement data,the parametric test was applied to compare the differences and correlations between the two subgroups in clinical and pathological characteristics.Both univariable and multivariable logistic regression models were constructed to analyze the sources of differences.To investigate the changing pattern of HER-2 expression status before and after neoadjuvant therapy and the difference in pathological complete remission(p CR)rate,theχ~2test and paired-sample parametric test were used to compare the sources of differences,and logistic regression models were constructed to investigate the correlated factors affecting p CR.Finally,the impact of HER-2 expression status on patient prognosis was investigated using Cox risk proportional model.Results:1.The percentage of triple-negative breast cancer was significantly higher in the HER-2zero expression group than the low expression group,and the percentage of Luminal type was significantly higher in the HER-2 low expression group than in the zero expression group.The percentage of luminal type was significantly higher than that of the zero expression group.2.There was a significant difference in the age distribution between the HER-2 low expression group and the HER-2 zero expression group,with a higher proportion of patients under 40 years of age in the HER-2 zero expression group.3.The percentage of Ki-67 high expression in the HER-2 zero expression group was significantly higher than that in the low expression group.In the analysis of variance and correlation analysis,it was confirmed that the HER-2 low expression group tended to exhibit lower Ki-67 values.4.The rate of axillary lymph node metastasis was higher in the HER-2 low expression group,but there was no significant difference in the degree of metastasis.In contrast,in the young breast cancer subgroup,the difference in axillary lymph node metastasis rate was more significant between the two subgroups,and the HER-2 low expression group showed more severe axillary lymph node metastasis.Meanwhile,HER-2 expression status was correlated with the degree of axillary lymph node metastasis.5.Among HER-2 negative breast cancer patients treated with neoadjuvant therapy,the p CR was higher in the HER-2 zero expression group,but the difference was not statistically significant,and HER-2 expression status did not have a significant impact on p CR outcome.Before and after neoadjuvant therapy,HER-2 expression status was unstable,mostly from"zero expression"to"low expression".Therefore,in clinical application,HER-2 expression status should be used as a dynamic assessment index to develop more accurate individualized treatment plans.6.In HER-2 negative breast cancer,there was no significant difference in prognosis between the HER-2 low expression breast cancer and HER-2 zero expression groups,regardless of HR status.However,the present study confirmed that high HR expression with low Ki-67 values was associated with a positive prognosis.Based on the correlation between HER-2 expression status and high HR,low Ki-67,and considering the effect of HER-2expression status on prognosis from the synergistic effect of other pathological parameters,HER-2 low expression status may still be a predictor of a positive prognosis.Conclusion:1.Compared with the HER-2 zero expression group,the HER-2 low expression group showed a higher degree of tumor differentiation and a lower degree of tumor proliferation.2.In the young breast cancer and triple-negative breast cancer groups,the HER-2 low expression group showed a more severe degree of axillary lymph node metastasis compared with the HER-2 zero expression group,which was associated with a poor prognosis.3.Compared with HER-2 low expression breast cancer,zero HER-2 expression was not an independent risk factor for poor prognosis.