Clinicopathological Characteristics And Prognosis Of Early-stage HER-2 Low-expression Breast Cancer

Background and Purpose: In recent years,breast cancer has replaced lung cancer as the most prevalent malignancy in women worldwide,posing a serious threat to women’s health and quality of life.HER-2 is an important indicator of breast cancer staging and treatment,and overexpression of human epidermal growth factor receptor 2(HER-2)is present in approximately 15-20% of breast cancer patients,and in the absence of treatment,HER-2overexpression is associated with a worse prognosis.In the absence of treatment,HER-2overexpression is associated with a worse prognosis.Owing to the emergence of drugs targeting human epidermal growth factor receptor 2(HER-2),remarkable prognostic enhancement has been seen for patients with HER-2-positive breast carcinoma.However,anti-HER-2 medicines are applicable merely to individuals with HER-2-positive tumors,and the benefit for those with low HER-2 expression is unclear.The DESTINY-Breast04 phase III and RC48 clinical trial results showed the benefit of antibody-drug couples for low HER-2-expressing individuals with breast carcinoma.Hence,the purposes of the present work are to explore the clinicopathological traits and prognostic differences in the HER-2 low expression Chinese population with early-stage breast carcinoma.Methods: The entire newly-diagnosed female early-stage breast carcinoma patients with negative HER-2 expression,who received treatment at our center from January of 2008 to December of 2017,were enrolled.Exclusion criteria were breast carcinoma patients at stage IV,with positive HER-2 expression,insufficient HER-2 data,as well as lobular or ductal carcinoma in situ.A total of 4,598 patients were enrolled eventually into the analysis,of which 2,837 had HER-2 0 tumors and 1,761 had HER-2 low tumors.We gathered the clinicopathological information from the breast carcinoma database of Qingdao University Hospital,which encompassed demographics,tumor dimensions,state of lymph nodes,HER-2 level,ER and PR staining,histological grading,as well as Ki-67.Their survival and prognosis information was obtained by follow-up.The median follow-up time was 71 months.Difference comparisons were made between HER-2 0 and HER-2 low groups regarding the clinical traits and outcomes.Results:1.Clinicopathological features of HER-2 low expression breast cancer:A total of 4598 patients were enrolled in this study,including 2837 patients with zero HER-2 expression and 1761 patients with low HER-2 expression.Of the 1761 patients with low HER-2expression tumors,1487(32.3%)were HER-2 IHC1+ and 274(5.9%)were HER-2 IHC2+.We found a higher proportion of HR positivity in patients with HER-2 low-expressing tumors compared with patients with HER-2 zero-expressing tumors(80.9% vs.77.8%,p<0.05).In addition,a higher number of HER-2-low-expressing tumors was found in the HR-positive subgroup than in the HR-negative subgroup(39.3% versus 34.8%,p< 0.05).In contrast to HER-2 0 tumors,the HER-2 low tumors were linked to an older median age at diagnosis,T1 tumors,N1 stage,a higher Ki-67 index,as well as inferior histological grade.In terms of surgical modality,the proportion of total mastectomy was slightly higher in the group with zero HER-2 expression(76.8% vs.73.7%,P=0.046).There was no significant difference between the two groups in terms of adjuvant radiotherapy(P=0.263)and chemotherapy(P=0.077),and a higher proportion of patients in the HER-2 low expression group received endocrine therapy due to the higher proportion of hormone receptor positive patients(P=0.017).2.Prognosis of HER-2 low expression breast cancer:Insignificant inter-group difference was noted regarding overall survival(OS),although the HER-2–0 group exhibited better disease-free survival(DFS)than the HER-2 low group for the entire(P = 0.003),HRpositive(P = 0.007)and lymph node-negative(P = 0.009)populations.3.Univariate and multivariate analyses:According to the univariate findings,tumor size,lymph node stage,hormone receptor negativity,high histologic grade,high Ki-67 and low HER-2 level were linked to inferior DFS for the entire included patients.In multivariate analysis,tumor size,lymph node stage,hormone receptor negativity,high histologic grade,high Ki-67 and low HER-2 level were linked to inferior DFS for the entire enrolled patients.Univariate and multivariate analyses showed similar results among the HR-positive population.But in the lymph node-negative population,hormone receptor negativity,high Ki-67 and low HER-2 level were linked to poorer DFS.In multifactorial analysis,correlations of hormone receptor negativity,high Ki-67,as well as low HER-2 level with poorer DFS were noted among the lymph node-negative population.Multivariate regression analysis confirmed low HER-2 expression was an inferior DFS prognostic factor in the HER-2-negative population with early-stage breast cancer(HR,1.33;95% CI,1.06–1.66;P = 0.013).Conclusions: The clinical traits of the HER-2 low carcinomas differed from those of HER-2–0 tumors.Despite the insignificant inter-group difference in OS,the differences in DFS were found for the overall,HR-positive and lymph node-negative subjects,suggesting the possibility of HER-2 low as an inferior prognostic factor for disease progression in earlystage breast cancer.