| Background:Although achieving pathological complete response(pCR)and nearpathological complete response(near-pCR)after neoadjuvant therapy(NAT)in breast cancer predicts a better outcome,some patients still experience recurrence.The aim of our study was to investigate whether near-pCR and pCR have comparable outcomes and to analyze the predictive risk factors of recurrence in the pCR and near-pCR population.Methods:Patients receiving NAT between January 2010 and April 2021 in the Cancer Hospital,Chinese Academy of Medical Sciences were reviewed retrospectively.Patients achieving pCR and near-pCR after NAT were included.Clinical and pathological features,and follow-up information were collected.pCR was defined as ypT0NO/ypTisN0.NearpCR was defined as ypT1mi/1a/1bN0 or ypT0/isN1mi.Kaplan-Meier method was used to calculate survival curves,and the Log-rank test was used to compare the difference in survival between the pCR and near-pCR groups.Log-rank test was used for univariate analysis and Cox proportional hazards model was used for multivariate analysis of risk factors for recurrence.Results:We reviewed 1209 breast cancer patients treated with NAT,and 292 patients were included according to the admission criteria.Of the 292 patients,173 were pCR and 1 19 were near-pCR.The median age was 46 years(range,23-75 years).The predominant tumor subtypes were human epidermal growth factor receptor type 2(HER2)positive breast cancer(49.0%)and triple-negative breast cancer(TNBC)(30.8%).The median follow-up was 53 months(range,9-138 months).A total of 25(8.6%)patients developed recurrence,with 9(5.2%)in the pCR group and 16(13.4%)in the near-pCR group.The vast majority(84.0%)of recurrence occurred within 36 months.The 5-year recurrencefree survival(RFS)rate of patients achieving pCR was significantly higher than that of patients achieving near-pCR(94.6%vs.85.6%,P=0.008).But the 5-year overall survival(OS)rate between the two cohorts had no statistical difference(94.3%vs.89.6%,P=0.304).Clinical N3(cN3)before NAT was an independent risk factor of recurrence for patients who achieved pCR(P=0.003)and near-pCR(P=0.036).Tumor size before NAT,subtypes of breast cancer,and chemotherapy regimens showed no significant association with recurrence both for patients who achieved pCR and near-pCR(P>0.05).Conclusions:cN3 before NAT was an independent risk factor of recurrence for patients who achieved pCR and near-pCR.It is worthwhile to monitor closely for patients with cN3,especially in the first 3 years.It needs to be further explored whether intensive adjuvant therapy should be given to these patients in the future.Background:Trastuzumab and pertuzumab gives additional hope for human epidermal growth Fator receptor type 2(HER2)positive breast cancer patients.Neoadjuvant trastuzumab and pertuzumab combined with chemotherapy regimens significantly increased pathological complete response(pCR)rate and survival for early HER2-positive breast cancers.But since pertuzumab come into the market of China in 2019,large realworld data are lacking.This study aimed to investigate the efficacy,safety,tolerability,factors influencing the efficacy,and survival of HER2-positive breast cancer patients receiving neoadjuvant treatment with trastuzumab,pertuzumab,taxane,and carboplatin(TCbHP)in real-world.Methods:The clinical and pathological data of HER2-positive breast cancer treated with TCbHP neoadjuvant therapy were prospectively collected from August 2019 to October 2022 at the the Cancer Hospital of the Chinese Academy of Medical Sciences,Huanxing Cancer Hospital of Beijing,and Sanhuan Cancer Hospital of Beijing.Survival data were obtained by follow-up.pCR was defined as ypT0N0/ypTisN0.Disease-free survival(DFS)was calculated by the Kaplan-Meier method.The difference between groups were calculated using Chi-square test.The factors influencing the efficacy were analyzed by logistic regression.Results:A total of 252 eligible patients with early HER2-positive breast cancer were enrolled according to the admission criteria after screening 792 breast cancer patients receiving neoadjuvant therapy.The median age was 48 years(range:20-72).Patients with stage Ⅱ and Ⅲ were 29.4%and 69.4%,respectively.A total of 139 patients achieved pCR,the pCR rate was 55.2%.The pCR rates of hormone receptor(HR)negative and positive were 72.3%(68/94)and 44.9%(71/158),respectively.The pCR rates of neoadjuvant regimen including docetaxel,paclitaxel,and albumin-paclitaxel were 50.0%(41/82),50.0%(57/114),and 73.2%(41/56),respectively.HR status(HR-vs.HR+,odd ratio[OR]=2.87,95%confidence interval[CI]:1.57-5.23,P=0.001),the neoadjuvant regimen of taxanes(albumin-binding paclitaxel vs.paclitaxel,OR=2.42,95%CI:1.14-5.13,P=0.021;albuminbinding paclitaxel vs.docetaxel,OR=2.46,95%CI:1.11-5.47,P=0.027),HER2 expression(HER2+FISH+vs.HER2 3+,OR=0.23,95%CI:0.10-0.57,P=0.001),and clinical tumor size(cT)before neoadjuvant therapy(cT1-2 vs.cT3-4,OR=3.33,95%CI:1.67-6.64,P=0.001)were the main factors influencing pCR.During neoadjuvant therapy,22 patients(8.7%)reduced the dose of taxanes and 42 patients(16.6%)reduced the dose of carboplatin.The most common grade 3 or 4 adverse events were neutropenia(9.9%).No serious cardiac events occurred.The 2-year DFS rate was 96.4%.Conclusions:This study suggest that the neoadjuvant TCbHP regimen for early HER2positive breast cancer has excellent efficacy,tolerance,survival,and manageable toxicity.TCbHP regimen can be used as neoadjuvant therapy for HER2-positive breast cancer patients in China.Albumin-binding paclitaxel showed a higher pCR rate and further validation in prospective cohorts is warranted.Background:The combination of trastuzumab and pertuzumab significantly increased the pathological complete responds(pCR)rate in early human epidermal growth factor receptor 2(HER2)positive breast cancer,but some patients are resistant to the treatment.Our study aimed to screen biomarkers related to the efficacy of trastuzumab and pertuzumab therapy and to provide valuable information for guiding follow-up treatment and research.Methods:We collected baseline tissue samples of HER2-positive breast cancer patients who received neoadjuvant treatment with trastuzumab/pertuzumab/taxane/carboplatin(TCbHP)from May 2021 to December 2022 at the Chinese Academy of Medical Sciences Cancer Hospital.Target sequence capture high-throughput genome sequencing and transcriptome testing were performed to describe variant events in HER2-positive early breast cancers.The genes,genome stability,and immune microenvironment on the efficacy of anti-HER2 therapy were analyzed,and the biomarkers were screened.Results:High-throughput genomic sequencing of baseline tissue specimens was performed in 40 patients with early HER2-positive breast cancer.The high-frequency variation genes are as follows:ERBB2 92.5%,TP53 87.5%,CDK12 70.0%,PIK3CA 30.0%,RARA 27.5%,PPM1D 25%,TOP2A 20.0%,KMT2C 20.0%,GNAS 20.0%,ZNF21720.0%,KMT2D 17.5%,ROS1 17.5%,HOXB13 17.5%,SPOP 15.0%,and GATA315.0%.There is one patient that did not undergo surgery.Of the 39 patients who had undergone surgery,19 achieved pCR and 20 non-pCR.No significant difference was observed in clinical and pathological features between the two groups.Patients with PIK3CA mutant have decreased pCR rate than patients with PIK3CA wild type(hazard ratio[HR]=13.47,95%confidence interval[CI]:1.39-130.91,P=0.025).Patients with SPOP amplification have decreased pCR rate than patients with SPOP wild type(P=0.047).A total of 28 patients whose RNA quality was eligible underwent whole-transcriptome sequencing successfully.One patient had not undergone surgery,and of the 27 patients who had undergone surgery,15 achieved pCR and 12 non-pCR.The high expression of ERBB2 mRNA(P=0.004)and CDK12 mRNA(P<0.001)were correlated with increased pCR rate.The high expression of CD8 effector memory T cells(CD8 Tem)(P=0.008)、Plasmacytoid Dendritic Cells,pDC(P=0.012)、T helper 2 cells(Th2)(P=0.022)were correlated with increased pCR rate.The high expression of fibroblasts(P=0.014)and Hematopoietic Stem Cells(HSC)(P=0.034)were correlated with decreased pCR rate.Conclusions:At the DNA level,PI3KCA mutation and SPOP gene amplification were associated with decreased pCR rate.At the RNA level,the high expression of ERBB2 mRNA and CDK12 mRNA were correlated with increased pCR rate.In the immune microenvironment,the high expression of CD8 Tem,pDC,and Th2 was correlated with increased pCR rate,and the high expression of fibroblast and HSC correlated with the decreased pCR rate.It is warranted to further explore and better illuminate the utility of these biomarkers in future clinical trials and clinical practice. |
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