The Prognostic Value Of Node Status And Molecular Sub-types In Breast Cancer With 4 Or More Positive Lymph Nodes :A Population-based Study SEER Database

Background:Breast cancer is the leading cause of cancer releated death among women all over the world.And the most commonly diagnosed cancer types in China.Nodal metastasis is a well known indicator of distance metastasis and positive lymph nodes usually associated with a poor survival outcome compare with patients with lymph node negative.Molecular type based on the high throughput technology is also a well established prognostic indicator of breast cancer patients which has revolutionized the opinions and the treatment of breast cancer.Although breast cancer subtypes were initially described and classified by molecular subtypes,the traditional IHC based molecular type showed the highly consistency with the genetic expression,conferring the similar prognostic values.So in our study,we took IHC as a standard way of molecular subtype classification.So far as we know,the relation between nodal metastases and BCS,and the prognostic value of nodal metastases in different BCS are still remains unclear.According to the2011^thh St.Gallen conference,breast cancer patients with 4 or more lymph nodes metastasis as the high risk groups usually had poor outcome.The treatment remedy never considered lymph node metastasis anymore.But for those patients,how lymph node metastasis burden affect patients’outcome in different breast cancer subtypes was still not clear.There was paramount necessity to deeply investigate the relation between lymph node burden and prognosis in molecular subtypes finally help to make the precise treatment plan.Objective:Our aim was to investigate the relation between nodal metastases and BCS of breast cancer patients with 4 or more lymph nodes metastasis,and the prognostic value of nodal metastases in the different BCS.Methods:Data from the Surveillance,Epidemiology and End Results database（2010–2013）were used to identify 6502 patients with 4 or more lymph nodes metastasis.Patients were subdivided into 4 subgroups including HoR+/HER2-,HoR+/HER2+,HoR-/HER2+,and triple negative breast cancer（TNBC）.And we assessed the effects of lymph node（LN）status on breast cancer-specific survival（BCSS）.Statistical comparisons of clinical outcomes and other clinicopathological data were assessed with SPSS software version25.0.The Kaplan-Meier method,log-rank test and Cox univariate regression analysis（p<0.05was considered statistically significant）were used to evaluate the differences between the different pN stage subgroup and molecular subgroups.Results:According to the inclusion criteria,a total of 6502 breast cancer patients with 4 or more lymph nodes metastasis were finally enrolled in this retrospective study.Among them HoR+/HER2-are 4011（61.7%）,HoR+/HER2+are 962（14.8%）,HoR-/HER2+are 521（8.0%）,TNBC are1008（15.5%）.Lymph node metastasis pN=4-6 are 3221（49.5%）,pN=7-9 are 1405（21.6%）,pN≥10 are 1876（28.9%）.1.The clinicopathological characteristics of breast cancer patients with 4 or more axillary lymph node metastasis by molecular subtyping:HoR-/HER2+and TNBC subtype were more likely to be histological grade 3 and pN₃ lymph nodes metastasis.2.Univariate and multivariate analysis showed:race,tumor grade,tumor size,number of lymph nodes metastasis,molecular subtype,radiotherapy and chemotherapy were factors related to the survival outcome of breast cancer patients with 4 or more lymph nodes metastasis.3.Kaplan-Meier analysis revealed that patients in pN_≥1010 stage had an exceptionally poor prognosis:3-year BCSS rate was 88.5%in pN_4-6stage,82.5%in pN_7-9-9 stage,76.9%in pN_≥1010 stage（P<0.001）.4.In the 3-years BCSS of different molecular subtypes,TNBC had the most poor outcome.3-year BCSS rate was 89.4%in HoR+/HER2-,89.2%in HoR+/HER2+,82.5%in HoR-/HER2+,and 57.3%in TNBC.As to 3-year BCSS,the survival curves showed that there was no outstanding survival distinction between HoR+/HER2-and HoR+/HER2+patients（P=0.576）.5.When the analysis was stratified by pN stage we found that the patients with higher pN stage disease had bad prognostic than the patients with lower pN stage disease in every breast cancer subtype.However,there was no outstanding survival distinction in patients with pN_7-9-9 and pN_≥1010 stage disease in TNBC（P=0.07）and pN4-6,pN7-9 and pN≥10 stage disease inHoR-/HER2+and HoR+/HER2+disease。6.After the analysis was classified by breast cancer subtype,we found that TNBC had the bad prognostic in every pN stage.However,there were no outstanding survival distinction between HoR+/HER2-patients and HoR+/HER2+breast cancer subtype when patients in pN_4-6stage（P=0.279）.Conclusion:1.Among the inclusion patients HoR-/HER2+and TNBC patients usually with gradeⅢtumors.2.Among the inclusion patients HoR-/HER2+and TNBC patients usually with more than 10 lymph nodes metastasis.3.For breast cancer patients with 4 or more lymph nodes metastasis, as the pN stage increased patients’outcome decreased.There were singnificant difference between pN_4-6、pN_7-9-9 and pN_≥1010 groups.4.For breast cancer patients with 4 or more lymph nodes metastasis,TNBC had the worst outcome.HoR+/HER2-and HoR+/HER2+had no survival difference（P=0.576）.5.When breast cancer patients with 4 or more lymph nodes metastasis was stratified by pN stage we found that the patients with higher pN stage disease had bad prognostic than the patients with lower pN stage disease in TNBC and HoR+/HER2-disease.6.When breast cancer patients with 4 or more lymph nodes metastasis was stratified by molecular subtype TNBC had the worst outcome（p<0.001）.