Background The clinical benefit of T-DXd in advanced breast cancer with hormone receptor-positive(HR+),human epidermal growth factor receptor 2(HER2)-ultralow tumors in the DESTINY-Breast06 trial has drawn attention t...Background The clinical benefit of T-DXd in advanced breast cancer with hormone receptor-positive(HR+),human epidermal growth factor receptor 2(HER2)-ultralow tumors in the DESTINY-Breast06 trial has drawn attention to this subtype.Methods We re-evaluated 473 pathological specimens from 302 HER2-negative breast cancer patients in our next generation sequencing database,classifying HER2-negative status into HER2-ultralow,IHC 0 without membrane staining(MS−)and HER2-low.Clinicopathologic characteristics and genomic profiles were analyzed by HER2 status.Results Overall,35.5%of primary and 49.0%of metastatic HER2-IHC 0 tumors were reclassified as ultralow.Subtype analysis based on HR status showed no distinct clinicopathological characteristics in the HER2-ultralow subgroup.Upon metastasis,40%of HER2-ultralow primary tumors converted to IHC 0(MS−)and 46.7%to HER2-low.In the metastatic tumors,60%of HER2-IHC 0(MS−)and 50%of HER2-ultralow translated to other HER2 statuses in re-obtained samples.HER2-ultralow status was associated with worse disease-free survival than HER2-IHC 0(MS−)and HER2-low status in HR-negative breast cancer,but no differences of overall survival were observed.The median progression-free survival for first-line chemotherapy was 7.2 months in HR+HER2-low,6.8 months in ultralow,and 8.8 months in IHC 0(MS−)patients(P=0.06).PIK3CA mutations were more common in the HER2-low subtype than in HER2-ultralow tumors in the HR−subtype.Conclusion In conclusion,HER2-ultralow status is not associated with distinct clinicopathologic or genomic characteristics.HER2-IHC 0(MS−)and ultralow statuses often coexist within the same patient.展开更多
The DESTINY-Breast04(DB-04)trial is a phaseⅢclinical trial that examined the efficacy of trastuzumab deruxtecan(T-DXd),an anti-HER2-antibody drug,in patients with low HER2 expression(HER2-low)advanced breast cancer.T...The DESTINY-Breast04(DB-04)trial is a phaseⅢclinical trial that examined the efficacy of trastuzumab deruxtecan(T-DXd),an anti-HER2-antibody drug,in patients with low HER2 expression(HER2-low)advanced breast cancer.The study enrolled patients with HER2-low,unresectable,and/or recurrent metastatic breast cancer(mBC)who were resistant to previous endocrine therapy and had received one or two previous lines of chemotherapy.Among the 557 enrolled patients,494(88.7%)patients had hormone receptor-positive(HR+)mBC and 63(11.3%)patients had hormone receptor-negative(HR−)mBC.展开更多
目的对人表皮生长因子受体2(HER-2)低表达乳腺癌的临床特征、抗体偶联药物(antibody drug conjugates,ADCs)在HER-2低表达人群的治疗进展进行总结。方法以“HER-2 low breast cancer、antibody drug conjugates”为英文关键词在PubMed...目的对人表皮生长因子受体2(HER-2)低表达乳腺癌的临床特征、抗体偶联药物(antibody drug conjugates,ADCs)在HER-2低表达人群的治疗进展进行总结。方法以“HER-2 low breast cancer、antibody drug conjugates”为英文关键词在PubMed数据库进行检索,检索时间为自建库至2022年12月。纳入标准:(1)HER-2低表达乳腺癌的生物学和临床特征;(2)ADCs药物的临床前试验和临床试验。排除标准:(1)个案报道;(2)重复的临床试验。最终纳入50篇文献。结果随着ADCs药物临床数据的不断公布,HER-2低表达乳腺癌的概念逐渐被重视。HER-2低表达乳腺癌有望成为一个全新的治疗亚型。以T-Dxd为代表的ADCs药物,包括Trastuzumab-emtansine、Trastuzumab-deruxtecan、Trastuzumab-Duocarmazine、ARX-788、XMT-1522、MEDI4276、A166和MRG002已经在HER-2低表达乳腺癌人群中展示出较好的疗效,相信新型ADCs在不久的未来能够成为HER-2低表达乳腺癌人群的治疗新选择。结论以T-Dxd为代表的新型ADCs的不断问世将成为HER-2低表达乳腺癌人群的治疗新选择,并改善该人群的预后。展开更多
The identification of HER2-low metastatic breast cancer as a novel subgroup with therapeutic implications underscores the intricacies in breast cancer classification.This subset,comprising 45%-60%of breast cancer case...The identification of HER2-low metastatic breast cancer as a novel subgroup with therapeutic implications underscores the intricacies in breast cancer classification.This subset,comprising 45%-60%of breast cancer cases,presents a challenge due to its heterogeneous nature,characterized by varying HER2 protein expression levels.This heterogeneity complicates diagnosis and treatment decisions.The advent of trastuzumab deruxtecan(T-DXd),a second-generation antibody-drug conjugate(ADC),instills renewed hope for HER2-low breast cancer patients,having demonstrated effectiveness in clinical trials.The article also explores the evolution of HER2 testing guidelines,notably the 2023 ASCO/CAP guidelines that acknowledge the potential benefits of HER2-targeted therapies for this subgroup.In summary,this article emphasizes the significance of collaborative efforts between Pathologists and Oncologists in the era of precision medicine.It also highlights the potential for innovative,tailored therapies for HER2-low breast cancer,promising enhanced treatment outcomes and a broader range of therapeutic options.展开更多
基金supported by grants from the National Natural Science Foundation of China(grant No.81903084 to J.J.,82303646 to G.D.C.,and 82473071 to H.X.C.)the Program for Shanghai Outstanding Academic Leader(grant No.LJRC2102 to H.X.C.)the Shanghai Anticancer Association SOAR PROJECT(grant No.SACA-AX202106 to H.X.C.).
文摘Background The clinical benefit of T-DXd in advanced breast cancer with hormone receptor-positive(HR+),human epidermal growth factor receptor 2(HER2)-ultralow tumors in the DESTINY-Breast06 trial has drawn attention to this subtype.Methods We re-evaluated 473 pathological specimens from 302 HER2-negative breast cancer patients in our next generation sequencing database,classifying HER2-negative status into HER2-ultralow,IHC 0 without membrane staining(MS−)and HER2-low.Clinicopathologic characteristics and genomic profiles were analyzed by HER2 status.Results Overall,35.5%of primary and 49.0%of metastatic HER2-IHC 0 tumors were reclassified as ultralow.Subtype analysis based on HR status showed no distinct clinicopathological characteristics in the HER2-ultralow subgroup.Upon metastasis,40%of HER2-ultralow primary tumors converted to IHC 0(MS−)and 46.7%to HER2-low.In the metastatic tumors,60%of HER2-IHC 0(MS−)and 50%of HER2-ultralow translated to other HER2 statuses in re-obtained samples.HER2-ultralow status was associated with worse disease-free survival than HER2-IHC 0(MS−)and HER2-low status in HR-negative breast cancer,but no differences of overall survival were observed.The median progression-free survival for first-line chemotherapy was 7.2 months in HR+HER2-low,6.8 months in ultralow,and 8.8 months in IHC 0(MS−)patients(P=0.06).PIK3CA mutations were more common in the HER2-low subtype than in HER2-ultralow tumors in the HR−subtype.Conclusion In conclusion,HER2-ultralow status is not associated with distinct clinicopathologic or genomic characteristics.HER2-IHC 0(MS−)and ultralow statuses often coexist within the same patient.
文摘The DESTINY-Breast04(DB-04)trial is a phaseⅢclinical trial that examined the efficacy of trastuzumab deruxtecan(T-DXd),an anti-HER2-antibody drug,in patients with low HER2 expression(HER2-low)advanced breast cancer.The study enrolled patients with HER2-low,unresectable,and/or recurrent metastatic breast cancer(mBC)who were resistant to previous endocrine therapy and had received one or two previous lines of chemotherapy.Among the 557 enrolled patients,494(88.7%)patients had hormone receptor-positive(HR+)mBC and 63(11.3%)patients had hormone receptor-negative(HR−)mBC.
文摘目的对人表皮生长因子受体2(HER-2)低表达乳腺癌的临床特征、抗体偶联药物(antibody drug conjugates,ADCs)在HER-2低表达人群的治疗进展进行总结。方法以“HER-2 low breast cancer、antibody drug conjugates”为英文关键词在PubMed数据库进行检索,检索时间为自建库至2022年12月。纳入标准:(1)HER-2低表达乳腺癌的生物学和临床特征;(2)ADCs药物的临床前试验和临床试验。排除标准:(1)个案报道;(2)重复的临床试验。最终纳入50篇文献。结果随着ADCs药物临床数据的不断公布,HER-2低表达乳腺癌的概念逐渐被重视。HER-2低表达乳腺癌有望成为一个全新的治疗亚型。以T-Dxd为代表的ADCs药物,包括Trastuzumab-emtansine、Trastuzumab-deruxtecan、Trastuzumab-Duocarmazine、ARX-788、XMT-1522、MEDI4276、A166和MRG002已经在HER-2低表达乳腺癌人群中展示出较好的疗效,相信新型ADCs在不久的未来能够成为HER-2低表达乳腺癌人群的治疗新选择。结论以T-Dxd为代表的新型ADCs的不断问世将成为HER-2低表达乳腺癌人群的治疗新选择,并改善该人群的预后。
文摘The identification of HER2-low metastatic breast cancer as a novel subgroup with therapeutic implications underscores the intricacies in breast cancer classification.This subset,comprising 45%-60%of breast cancer cases,presents a challenge due to its heterogeneous nature,characterized by varying HER2 protein expression levels.This heterogeneity complicates diagnosis and treatment decisions.The advent of trastuzumab deruxtecan(T-DXd),a second-generation antibody-drug conjugate(ADC),instills renewed hope for HER2-low breast cancer patients,having demonstrated effectiveness in clinical trials.The article also explores the evolution of HER2 testing guidelines,notably the 2023 ASCO/CAP guidelines that acknowledge the potential benefits of HER2-targeted therapies for this subgroup.In summary,this article emphasizes the significance of collaborative efforts between Pathologists and Oncologists in the era of precision medicine.It also highlights the potential for innovative,tailored therapies for HER2-low breast cancer,promising enhanced treatment outcomes and a broader range of therapeutic options.
