Analysis Of The Influencing Factors Related To HER2-Zero And HER2-Low Expression On The Efficacy Of Neoadjuvant Chemotherapy In HR-Positive Breast Cancer

Background:Breast cancer has come up to the first place of incidence rate of female malignancies.In this regard,several effective treatment strategies and diagnose methods have been continuously developed during the last decades which have greatly improved prognosis.As one of the effective therapeutic strategies,neoadjuvant therapy brings possibility of surgery for inoperable patients and increases opportunities for breast conserving surgery,prompts the patient’s sensitivity and tolerance to drugs in order to provide a basis for formulating follow-up treatment plans.Traditionally,the classification of breast cancer relies on the expression of hormone receptor(HR)and human epidermal growth factor receptor 2(HER2)status which also determines the therapeutics in different molecular.The abnormal amplification of HER2 is one of the poor prognosis factors.In fact,the definition of HER2 expression status is more than dichotomous.According to statistics,about 50% of HER2-negative patients shows low expression of HER2,which is commonly defined as immunohistochemistry(IHC)1+ or IHC 2+ without simultaneous fluorescence in situ hybridization(FISH)amplification.Nevertheless,patients with HER2-low expression breast cancer obtained limited efficacy through traditional targeted drugs like trastuzumab.Only a small number of patients can achieve pathological complete response(p CR)among those with HR-positive/HER2-negative breast cancer by taking neoadjuvant chemotherapy.The clinicopathological characteristics of patients with HER2-low expression breast cancer and their response to neoadjuvant chemotherapy attract researchers’ attention,while none unified conclusions and standard therapeutic options have been reached currently.Further discussion and research are still needed.Objective:1.To explore the clinicopathological features of HER2-low expression as a potential new classification;2.To compare the p CR rate of HER2-zero and HER2-low expression and perform subgroup analysis;3.To analyze the influencing factors of neoadjuvant chemotherapy in the HER2-zero group and the HER2-low expression group.Materials and methods:We incorporated 117 patients who were diagnosed as HR-positive HER2-negative breast cancer during August 2018 to May 2022 in the department of Breast Surgery,a class III hospital affiliated to Jilin University.The initial treatment of patients was neoadjuvant chemotherapy and ultimately received surgery.Retrospective analysis methods are used and relevant data analysis is carried out with statistical software.The clinical data we collected include: age,menstrual state,body mass index,tumor T stage,axillary lymph node status,expression level of Estrogen receptor(ER),Progesterone receptor(PR),HER2 and Ki-67,Miller-Payne stage and(non-)pathological complete response.The measurement data was expressed by` x ± s and intergroup analysis was carried out by t-test.The counting data was expressed as number(%)and compared between groups using chi-square test or rank sum test.Univariate Logistic regression was used to analyze the independent influencing factors of neoadjuvant chemotherapy efficacy of Luminal breast cancer patients in the HER2-zero and HER2-low expression groups.Differences with p <0.05 were considered statistically significant.Result:1.117 patients were enrolled in this study,including 36 cases of HER2-zero(30.8%),81 cases of HER2-low expression(30.8%).Age ranged from 29 to 73 years old,median age is 49 years old.Patients of HER2-low expression had more axillary lymph node metastases than HER2-zero(90.1%VS75.0%,p=0.032)and a higher PR status(p=0.027).2.The p CR rate of HER2-zero and HER2-low expression are randomly 8.3% and 4.9%(p=0.77),a lower rate showed in HER2-low expression but there is no statistical significance,neither while comparing the difference between IHC0,IHC1+ and IHC2+/FISH-(p=0.709).3.Single factor analysis showed that,in HER2-zero group,high ER status is related to worse neoadjuvant chemotherapy efficacy(p=0.042);PR status is also the affecting factor in HER2-zero group which is negatively correlated with neoadjuvant chemotherapy effect(p=0.03).PR status is associated with a worse outcome of neoadjuvant chemotherapy in patients with HER2-low expression(p=0.018).Conclusion:1.HER2-low expression(IHC1+,IHC2+/FISH-)is a classification with distinct pathological characteristics and different from HER2-zero in HR-positive breast cancer.2.There is no difference between HER2-zero and HER2 low expression in pathological complete response rates of HR-positive breast cancer after neoadjuvant chemotherapy.3.ER and PR status are directly related in the efficacy of neoadjuvant chemotherapy for HR-positive HER2-zero breast cancer.PR status is the influencing factor of the neoadjuvant chemotherapy efficacy of HR-positive HER2-low expression breast cancer.