Effect Of Her-2 Protein Expression Intensity On The Efficacy And Prognosis Of Neoadjuvant Chemotherapy In Triple Negative Breast Cancer

Research backgroundBreast cancer has become a global disease threatening the health of women and is one of the most common malignant tumors in women.Among the molecular subtypes of the breast,triple-negative breast cancer(TNBC)is a special subtype of breast cancer,accounting for 15% to 25% of breast cancer patients.Moreover,these patients are prone to early recurrence or metastasis,and the survival rate is lower than that of other subtypes of breast cancer.Treatment strategies for patients with TNBC are limited due to the lack of expression of specific receptors,and non-specific drug chemotherapy is currently recognized as a systemic therapy.In recent years,neoadjuvant chemotherapy(NAC)plays an increasingly important role in clinical practice.It can reduce tumor staging and increase the chances of breast-conserving surgery.It can also evaluate the sensitivity of tumors to chemotherapeutic drugs and improve the prognosis of breast cancer patients.Nowadays,NAC has become a standard treatment strategy for patients with TNBC,and patients who achieve complete pathological remission(p CR)after NAC have better long-term prognosis results.Although TNBC is more difficult to treat and has a poor prognosis than other subtypes,not all patients exhibit poor clinical outcomes.Studies have shown that breast cancer patients with low expression of human epidermal growth factor receptor-2(HER-2)protein can also benefit from targeted HER-2 therapy,which indicates that for patients with low expression of HER-2 protein,different expression intensities of HER-2 protein may have different prognosis results.In patients with TNBC,HER-2 protein is not expressed or is low in expression,but three different expression intensities of 0,1+ and 2+ are still present.However,there are few and controversial studies on the prognosis of low expression of HER-2 protein.In conclusion,it is necessary to further study the effect of different expression levels of HER-2 protein on the efficacy and prognosis of neoadjuvant chemotherapy in TNBC.ObjectiveThe prognosis of breast cancer patients with low expression of HER-2 protein is not the same,and its prognostic value needs further study.The purpose of this study was to investigate the effects of the expression levels of HER-2 proteins(0,1+,and 2+)in triple-negative breast cancer on the efficacy and prognosis of neoadjuvant chemotherapy.MethodsA total of 221 TNBC patients treated with NAC in the Department of Breast,Affiliated Tumor Hospital of Zhengzhou University from January 2014 to December2018 were retrospectively analyzed.According to the postoperative pathological results,it is determined whether p CR is achieved.p CR is defined as that there is no cancer cell residue in the primary breast lesion or only ductal carcinoma in situ,and there is no cancer cell infiltration in the lymph nodes,yp T0/isyp N0.Disease free survival(DFS),defined as the interval(in months)from the date of surgery to the date of reexamination for the discovery of local recurrence,distant metastasis,or contralateral invasive cancer,was determined through a follow-up system of outpatient visits that ended in October 2020.Enumeration data were presented as rates(%)and differences between groups were analyzed using Mann-Whitney U or Kruskal-Wallis H tests.The influencing factors related to p CR were screened by Chi-square test,and the independent influencing factors of p CR were further analyzed by multi-factor Logistic regression.The Kaplan-Meier(K-M)curve was used to evaluate the relationship between the expression intensity of different HER-2 proteins and the postoperative DFS rate,and Log-Rank test was performed.Univariate and multivariate Cox regression were used to analyze the independent prognostic factors.P < 0.05 indicated statistically significant.Results1.Among the 221 female patients enrolled in the study,the age ranged from 19 to77 years old(median 47 years old),and 32.1% of them achieved p CR status after NAC.The median follow-up time was 23 months,ranging from 1 to 73 months,and a total of 29.9%(66 patients)experienced recurrence or metastasis.2.There was no statistically significant correlation between the expression level of HER-2 protein and age,menstrual status,clinical T stage,clinical N stage,or Ki-67(P > 0.05).Baseline characteristics were generally consistent across subgroups of HER-2 protein expression intensities.3.Single factor analysis showed that the expression level of HER-2 protein was related to p CR(P < 0.05).Further multivariate analysis showed that the expression level of HER-2 protein was an independent factor affecting p CR(P < 0.05).4.K-M survival analysis showed that the expression level of HER-2 protein was negatively correlated with the DFS rate(P < 0.01).Multivariate analysis showed that the intensity of HER-2 expression was an independent prognostic factor(P < 0.05).ConclusionsIn patients with TNBC,the expression level of HER-2 protein is an important prognostic indicator.The lower the expression level,the easier it is to achieve p CR after NAC treatment and the better the prognosis will be.It should then be included as a risk factor in the prognosis of patients with TNBC.Meanwhile,the invention also provides ideas for searching potential therapeutic targets for breast cancer patients with low expression of HER-2 protein.