| Objective A retrospective analysis was conducted to include 1153HER2-negative patients in a single-center database from January 1,2014 to January 1,2020;to understand and compare the proportion of HER2 negative breast cancers with different levels of HER2 expression and differences in clinical molecular characteristics;Exploring the disease outcomes of HER2-negative breast cancer patients with varying levels of HER2 expression,this research will provide a guide for clinical formulation.so as to guide clinical decision making for precise treatment.Methods Exploring the disease outcomes of HER2-negative breast cancer patients with varying levels of HER2 expression,this research will provide a guide for clinical formulation.and were followed up by reviewing patients’outpatient or inpatient medical records,telephone and weibo.SPSS 26.0 and Graph Pad Prism 9.0 statistical software were used for statistical analysis and data processing.For counting data,t-test and ANOVA were applied,while chi-square test was utilized for measurement data.Exploring the disease outcomes of HER2-negative breast cancer patients with varying levels of HER2 expression,this research will provide a guide for clinical formulation.Results 1.Proportion of HER2-negative breast cancers with different levels of HER2 expression:1153HER2-negative patients were included in this study,of which 48.9%(564/1153),32.9%(379/1153),and 18.2%(210/1153).1.1 The proportion of HR+/HER2 negative patients was 79.7%(919/1153),of which 45.6%(419/919),35.4%(325/919),and 19.0%(175/919)were HER2 IHC0,HER2 IHC1+,and HER2 IHC2+/ISH-.1.2 The proportion of patients with triple negative breast cancer was 20.3%(234/1153),of which the proportions of HER2 IHC0,HER2 IHC1+,and HER2IHC2+/ISH-were 62.0%(145/234),23.1%(54/234),and 14.9%(35/234).2.Comparison of clinicopathological characteristics of breast cancer patients with different levels of HER2 expression in HER2-negative breast cancer2.1 Comparison of clinicopathological characteristics of patients with HER2IHC0,IHC1+,and IHC2+/ISH-breast cancer: in T-stage(χ2=7.376,P=0.025),TNM-stage(χ2=8.811,P=0.012),histological grade(χ2=13.875,P<0.001),and vascular/neural invasion(χ2=8.246,P=0.016),molecular staging(χ2=20.497,P<0.001),ER(χ2=22.403,P<0.001),PR(χ2=14.826,P<0.001),and Ki-67(χ2=7.640,P=0.022)were statistically different(P<0.05).There were no statistical differences in age,site of breast cancer,menopausal status,tumor size,axillary lymph node status,surgical modality,and radiation therapy(P>0.05).2.1.2 Comparison of clinicopathological features between HER2 IHC0 and IHC1+ breast cancer patients: histological grading(χ2=13.036,P<0.001),vascular/neural invasion(χ2=5.641,P=0.018),molecular staging(χ2=17.884,P<0.001),ER(χ2=20.557,P<0.001),PR(χ2=38.461,P<0.001),and Ki-67(χ2=4.151,P=0.042)were statistically different(P<0.05).There were no statistical differences in age,site of breast cancer,menopausal status,tumor size,T-stage,axillary lymph node status,TNM stage,surgical modality,and radiation therapy(P> 0.05).2.1.3 Comparison of clinicopathological characteristics between HER2 IHC0 and IHC2+/ISH-breast cancer patients: in axillary lymph node status(χ2=4.991,P=0.025),TNM stage(χ2=8.247,P=0.004),vascular/nerve invasion(χ2=6.135,P=0.013),molecular staging(χ2=7.011,P=0.008),ER(χ2=6.238,P=0.013),and PR(χ2=7.507,P=0.006)were statistically different(P<0.05).There were no statistical differences in age,site of breast cancer,menopausal status,tumor size,histological grade,T-stage,Ki-67,surgical modality,and radiation therapy(P>0.05).2.1.4 Comparison of clinicopathological characteristics between HER2 IHC1+ and IHC2+/ISH-breast cancer patients: there were statistical differences(P<0.05)in histological grading(χ2=5.781,P=0.016),TNM stage(χ2=7.174,P=0.007),and Ki-67(χ2=6.565,P=0.01).There were no statistical differences in age,site of breast cancer,menopausal status,tumor size,T-stage,choroidal/neural invasion,axillary lymph node status,molecular staging,ER,PR,surgical modality,and radiation therapy(P>0.05).2.2 Comparison of clinicopathological characteristics among HR+ breast cancer patients with HER2 IHC0,IHC1+,and IHC2+/ISH-breast cancer: there were statistical differences(P<0.05)in plexus/nerve invasion(χ2=7.407,P=0.025)and Ki-67(χ2=20.253,P<0.001).There were no statistical differences in age,site of breast cancer,menopausal status,tumor size,axillary T stage,TNM stage,histological grading,axillary lymph node status,surgical approach,and radiation therapy(P>0.05).2.2.1 Statistically,there were differences(P<0.05)between HR+/HER2 IHC0 and HR+/HER2 IHC1+ breast cancer patients in plexus/nerve invasion(χ2=6.335,P=0.012)and Ki-67(χ2=7.397,P=0.007)when comparing clinicopathological characteristics.Age,site of breast cancer,menopausal status,tumor size,T stage,TNM stage,histological grading,axillary lymph node status,surgical modality,and radiation therapy were not statistically significant.(P>0.05).2.2.2 Statistically,there were differences(P<0.05)between HR+/HER2 0 and HR+/HER2 1+ breast cancer patients in plexus/nerve invasion(χ2=6.335,P=0.012)and Ki-67(χ2=7.397,P=0.007)when comparing clinicopathological characteristics.Age,site of breast cancer,menopausal status,tumor size,T stage,TNM stage,histological grading,axillary lymph node status,surgical modality,and radiation therapy were not statistically significant.(P>0.05).2.2.3 Comparison of clinicopathological characteristics between HR+/HER21+ and HER2 2+/ISH-breast cancer patients: statistically different(P<0.05)on Ki-67(χ2=4.617,P=0.032).There were no statistical differences in age,site of breast cancer,menopausal status,tumor size,T stage,TNM stage,choroidal/neural invasion,histological grading,axillary lymph node status,surgical modality,and radiation therapy(P>0.05).2.3 Comparison of clinicopathological characteristics of HER2 IHC0,IHC1+,and IHC2+/ISH-breast cancer patients with triple-negative breast cancer: TNM stage(χ2=7.301,P=0.026),histological grading(χ2=15.462,P<0.001),Ki-67(χ2=9.283,P=0.01),respectively,and Radiation therapy(χ2=8.485,P=0.004)were statistically different(P<0.05).There were no statistical differences in age,site of breast cancer,menopausal status,tumor size,T-stage,TNM staging,plexus/nerve invasion,axillary lymph node status,or surgical approach(P>0.05).2.3.1 Comparison of clinicopathological characteristics among triple negative breast cancer patients with HER2 IHC0 and IHC1+ breast cancer: there were statistical differences(P<0.05)in histological grading(χ2=15.120,P<0.001),Ki-67(χ2=9.340,P=0.002),and radiation therapy(χ2=8.502,P=0.014).There were no statistical differences in age,site of breast cancer,menopausal status,tumor size,T-stage,plexus/nerve invasion,axillary lymph node status,or surgical approach(P>0.05).2.3.2 Statistically,there were differences(P<0.05)between HR+/HER2 IHC0 and HR+/HER2 IHC1+ breast cancer patients in plexus/nerve invasion(χ2=6.335,P=0.012)and Ki-67(χ2=7.397,P=0.007)when comparing clinicopathological characteristics.Age,site of breast cancer,menopausal status,tumor size,T stage,TNM stage,histological grading,axillary lymph node status,surgical modality,and radiation therapy were not statistically significant.(P>0.05).2.3.3 Comparison of clinicopathological characteristics of HER2 IHC1+ and HER2 2+/ISH-breast cancer patients with triple negative breast cancer: there were statistical differences(P<0.05)in TNM stage(χ2=6.228,P=0.013)and histological grading(χ2=7.832,P=0.005).There were no statistical differences in age,site of breast cancer,menopausal status,tumor size,T-stage,plexus/nerve invasion,axillary lymph node status,surgical modality,or radiation therapy(P>0.05).3.Survival analysis of different HER2 expression status among HER2-negative breast cancer patients.3.1 Comparison of disease-free survival rates among HER2-negative breast cancer patients with different HER2 expression status: the mean survival times of HER2 IHC0,HER2 IHC1+,and HER2 IHC2/ISH-were 82.5、94.7and 86.7 months,respectively,with statistical differences in disease-free survival rates among the three groups(P=0.0002).(P<0.05).3.2 Comparison of disease-free survival rates of breast cancer patients with different HER2 expression status in the HR+ cohort: The mean survival times of the HER2 IHC0,HER2 IHC1+,and HER2 IHC2+/ISH-groups were 83.4 months,94.8 months,and 86.9 months,respectively,and there was a statistical difference in the disease-free survival rates of the three groups(P=0.0031).(P<0.05).3.3 In triple-negative breast cancer HER2 IHC0,HER2 IHC1+ and HER2IHC2/ISH-the mean survival times of the three groups were 77.8 months,93.5months and 85.2 months,respectively,and there was no statistical difference in the disease-free survival rates of the three groups(P=0.1198).(P>0.05).4.Prognostic impact of clinicopathological characteristics on breast cancer patients with different HER2 expression status in HER2-negative breast cancer4.1 Univariate analysis of recurrence and metastatic events in HER20-expressing breast cancer patients revealed that histological grade,T-stage,N-stage,vascular/neural invasion and TNM stage were associated with the prognosis of HER2 0-expressing breast cancer patients(P<0.049,<0.0001,<0.001,<0.001,<0.001,<0.001);multifactorial Cox regression analysis confirmed that vascular/neural invasion,histological grade,T stage,N stage and TNM stage(P<0.006,<0.001,<0.015,<0.005)were associated with the prognosis of patients with HER2 0-expressing breast cancer.4.2 Univariate analysis of recurrence and metastatic events in HER21+-expressing breast cancer patients revealed that T-stage,N-stage and TNM-stage,and Ki-67 expression levels were associated with the prognosis of HER2IHC1+expressing breast cancer patients(P<0.004,<0.001,<0.001,<0.001);multifactorial Cox regression analysis confirmed that Ki-67,N staging(P=0.002,<0.001)were associated with the prognosis of HER2 IHC1+ expressing breast cancer patients.4.2 Univariate analysis of recurrence and metastatic events in HER2 2+/ISHoverexpressing breast cancer patients revealed that T stage,N stage and TNM stage were associated with the prognosis of HER2 2+/ISH-overexpressing breast cancer patients(P<0.001,< 0.005,<0.001),respectively;multifactorial Cox regression analysis confirmed that tumor T stage(P=0.013)correlated with the prognosis of patients with HER2 2+/ISH-overexpressing breast cancer.Conclusion 1.The highest proportion of HER2 IHC0 breast cancer patients among HER2 negative breast cancers followed by HER2 IHC1+,HER2 IHC2+/ISH-in 5 years at the General Hospital of Ningxia Medical University Cancer Hospital.HER2 IHC1+,HER2 IHC2+/ISH-tumors were significantly enriched in HR-positive breast cancer compared to HER2 IHC0 tumors,and HER2 IHC0 was more common in patients with TNBC.2.There were differences in clinicopathological features of HER2 expression in IHC0,IHC1+,and IHC2+/ISH-breast cancers,regardless of HR status,and differences in Ki-67 different expression levels in IHC0,IHC1+,and IHC2+/ISHpatients,with HER2 IHC0 being more susceptible to choroidal nerve invasion compared to HER2 IHC1+,IHC2+/ISH-,HER2 IHC1+ had a lower histological grade and TNM stage than IHC2+/ISH-.3.The clinical outcomes of breast cancer patients with different HER2 expression levels(IHC0,IHC1+,IHC2+/ISH-)were different,showing the best DFS for IHC1+ and the worst DFS for IHC0.However,there was no difference in survival time among the three in TNBC,suggesting that different therapeutic needs exist for patients with different HER2 protein expression in clinical practice. |
PDF Full Text Request