Objective:Lymphovascular invasion(LVI)is a crucial step in metastasis and is closely associated with poor prognosis in patients with breast cancer.However,its clinical and molecular characteristics remain insufficient...Objective:Lymphovascular invasion(LVI)is a crucial step in metastasis and is closely associated with poor prognosis in patients with breast cancer.However,its clinical and molecular characteristics remain insufficiently defined.We aimed to identify molecular targets for LVI-positive(LVI+)breast cancer and predict patient prognosis via the analysis of genomic variations using targeted sequencing.Methods:We established a large-scale targeted sequencing cohort of 4,079 breast cancer samples,which included 3,159 early-stage and locally advanced patients with available LVI statuses.Comparisons of somatic mutation frequencies and germline pathogenic/likely pathogenic(P/LP)mutation frequencies,mutational signature analyses,and mutual exclusivity and co-occurrence analyses were performed to identify key genomic features involved in LVI+patients.Additionally,Kaplan-Meier survival analysis was conducted to further explore the prognostic value of co-mutations in LVI+cases.Results:We observed that LVI+patients with the hormone receptor-positive/human epidermal growth factor receptor 2-negative(HR+/HER2-)and triple-negative breast cancer(TNBC)subtypes exhibited worse disease-free survival.Notably,HR+/HER2-and HER2+breast cancer patients with LVI displayed distinct genomic features compared with LVI-tumors.Specifically,LVI+HR+/HER2-tumors exhibited greater frequencies of somatic mutations in TP53 and ESR1,germline BRCA2 P/LP variations,and an enrichment of clock-like single-base substitution(SBS)1 mutational signatures.In contrast,LVI+HER2+tumors demonstrated a higher incidence of somatic PIK3CA mutations and increased activity of the apolipoprotein B m RNA editing enzyme catalytic polypeptide(APOBEC)-associated SBS2 signature.Furthermore,we revealed that the co-mutation of TP53 and NF1 could serve as a potential prognostic marker for LVI+HR+/HER2-patients.Conclusions:Our findings provide a comprehensive overview of the genomic characteristics of LVI in breast cancer,thereby offering insights that may help in refining precision treatment strategies for LVI+breast cancer patients.展开更多
Objective:Sentinel lymph node biopsy(SLNB)is currently the standard of care in clinically node negative(cN0)breast cancer.The present study aimed to evaluate the negative predictive value(NPV)of 18F-FDG dedicated lymp...Objective:Sentinel lymph node biopsy(SLNB)is currently the standard of care in clinically node negative(cN0)breast cancer.The present study aimed to evaluate the negative predictive value(NPV)of 18F-FDG dedicated lymph node positron emission tomography(LymphPET)in cN0 patients.Methods:This was a prospective phase II trial divided into 2 stages(NCT04072653).In the first stage,cN0 patients underwent axillary LymphPET followed by SLNB.In the second stage,SLNB was omitted in patients with a negative preoperative axillary assessment after integration of LymphPET.Here,we report the results of the first stage.The primary outcome was the NPV of LymphPET to detect macrometastasis of lymph nodes(LN-macro).Results:A total of 189 patients with invasive breast cancer underwent LymphPET followed by surgery with definitive pathological reports.Forty patients had LN-macro,and 16 patients had only lymph node micrometastasis.Of the 131 patients with a negative LymphPET result,16 patients had LN-macro,and the NPV was 87.8%.After combined axillary imaging evaluation with ultrasound and LymphPET,100 patients were found to be both LymphPET and ultrasound negative,9 patients had LN-macro,and the NPV was 91%.Conclusions:LymphPET can be used to screen patients to potentially avoid SLNB,with an NPV>90%.The second stage of the SOAPET trial is ongoing to confirm the safety of omission of SLNB according to preoperational axillary evaluation integrating LymphPET.展开更多
Objective： The indication of adjuvant chemotherapy recommendation（ACR） in breast cancer patients with intermediate recurrence score（RS） is controversial. This study investigated the relationship between routine c...Objective： The indication of adjuvant chemotherapy recommendation（ACR） in breast cancer patients with intermediate recurrence score（RS） is controversial. This study investigated the relationship between routine clinicopathological indicators and ACR, and established a nomogram for predicting the probability of ACR in this subset of patients.Methods： Data for a total of 504 consecutive patients with intermediate RS from January 2014 to December2016 were retrospectively reviewed. A nomogram was constructed using a multivariate logistic regression model based on data from a training set（378 cases） and validated in an independent validation set（126 cases）. A Youdenderived cut-off value was assigned to the nomogram for accuracy evaluation.Results： The multivariate logistic regression analysis identified that age, histological grade, tumor size, lymph node（LN） status, molecular subtype, and RS were independent predictors of ACR. A nomogram based on these predictors performed well. The P value of the Hosmer-Lemeshow test for the prediction model was 0.286. The area under the curve（AUC） values were 0.905 [95% confidence interval（95% CI）： 0.876–0.934] and 0.883（95%CI： 0.824–0.942） in the training and validation sets, respectively. The accuracies of the nomogram for ACR were84.4% in the training set and 82.1% in the validation set.Conclusions： We developed a nomogram to predict the probability of ACR in breast cancer patients with intermediate RS. This model may aid the individual risk assessment and guide treatment decisions in clinical practice.展开更多
基金supported by grants from the National Natural Science Foundation of China(No.82373303,No.82072922,No.82403750)a grant from the Natural Science Foundation of Shanghai(No.24ZR1412600)。
文摘Objective:Lymphovascular invasion(LVI)is a crucial step in metastasis and is closely associated with poor prognosis in patients with breast cancer.However,its clinical and molecular characteristics remain insufficiently defined.We aimed to identify molecular targets for LVI-positive(LVI+)breast cancer and predict patient prognosis via the analysis of genomic variations using targeted sequencing.Methods:We established a large-scale targeted sequencing cohort of 4,079 breast cancer samples,which included 3,159 early-stage and locally advanced patients with available LVI statuses.Comparisons of somatic mutation frequencies and germline pathogenic/likely pathogenic(P/LP)mutation frequencies,mutational signature analyses,and mutual exclusivity and co-occurrence analyses were performed to identify key genomic features involved in LVI+patients.Additionally,Kaplan-Meier survival analysis was conducted to further explore the prognostic value of co-mutations in LVI+cases.Results:We observed that LVI+patients with the hormone receptor-positive/human epidermal growth factor receptor 2-negative(HR+/HER2-)and triple-negative breast cancer(TNBC)subtypes exhibited worse disease-free survival.Notably,HR+/HER2-and HER2+breast cancer patients with LVI displayed distinct genomic features compared with LVI-tumors.Specifically,LVI+HR+/HER2-tumors exhibited greater frequencies of somatic mutations in TP53 and ESR1,germline BRCA2 P/LP variations,and an enrichment of clock-like single-base substitution(SBS)1 mutational signatures.In contrast,LVI+HER2+tumors demonstrated a higher incidence of somatic PIK3CA mutations and increased activity of the apolipoprotein B m RNA editing enzyme catalytic polypeptide(APOBEC)-associated SBS2 signature.Furthermore,we revealed that the co-mutation of TP53 and NF1 could serve as a potential prognostic marker for LVI+HR+/HER2-patients.Conclusions:Our findings provide a comprehensive overview of the genomic characteristics of LVI in breast cancer,thereby offering insights that may help in refining precision treatment strategies for LVI+breast cancer patients.
基金supported by the Ministry of Education Innovation Team(Grant No.IRT1223)and the Shanghai Health System Joint Project of Key Disease(Grant No.2013ZYJB0302).
文摘Objective:Sentinel lymph node biopsy(SLNB)is currently the standard of care in clinically node negative(cN0)breast cancer.The present study aimed to evaluate the negative predictive value(NPV)of 18F-FDG dedicated lymph node positron emission tomography(LymphPET)in cN0 patients.Methods:This was a prospective phase II trial divided into 2 stages(NCT04072653).In the first stage,cN0 patients underwent axillary LymphPET followed by SLNB.In the second stage,SLNB was omitted in patients with a negative preoperative axillary assessment after integration of LymphPET.Here,we report the results of the first stage.The primary outcome was the NPV of LymphPET to detect macrometastasis of lymph nodes(LN-macro).Results:A total of 189 patients with invasive breast cancer underwent LymphPET followed by surgery with definitive pathological reports.Forty patients had LN-macro,and 16 patients had only lymph node micrometastasis.Of the 131 patients with a negative LymphPET result,16 patients had LN-macro,and the NPV was 87.8%.After combined axillary imaging evaluation with ultrasound and LymphPET,100 patients were found to be both LymphPET and ultrasound negative,9 patients had LN-macro,and the NPV was 91%.Conclusions:LymphPET can be used to screen patients to potentially avoid SLNB,with an NPV>90%.The second stage of the SOAPET trial is ongoing to confirm the safety of omission of SLNB according to preoperational axillary evaluation integrating LymphPET.
文摘Objective： The indication of adjuvant chemotherapy recommendation（ACR） in breast cancer patients with intermediate recurrence score（RS） is controversial. This study investigated the relationship between routine clinicopathological indicators and ACR, and established a nomogram for predicting the probability of ACR in this subset of patients.Methods： Data for a total of 504 consecutive patients with intermediate RS from January 2014 to December2016 were retrospectively reviewed. A nomogram was constructed using a multivariate logistic regression model based on data from a training set（378 cases） and validated in an independent validation set（126 cases）. A Youdenderived cut-off value was assigned to the nomogram for accuracy evaluation.Results： The multivariate logistic regression analysis identified that age, histological grade, tumor size, lymph node（LN） status, molecular subtype, and RS were independent predictors of ACR. A nomogram based on these predictors performed well. The P value of the Hosmer-Lemeshow test for the prediction model was 0.286. The area under the curve（AUC） values were 0.905 [95% confidence interval（95% CI）： 0.876–0.934] and 0.883（95%CI： 0.824–0.942） in the training and validation sets, respectively. The accuracies of the nomogram for ACR were84.4% in the training set and 82.1% in the validation set.Conclusions： We developed a nomogram to predict the probability of ACR in breast cancer patients with intermediate RS. This model may aid the individual risk assessment and guide treatment decisions in clinical practice.
