Objective:Endocrine therapy with fulvestrant has shown synergistic antitumor effects with some chemotherapy drugs in vitro.This study evaluated the efficacy and safety of fulvestrant with vinorelbine in patients with ...Objective:Endocrine therapy with fulvestrant has shown synergistic antitumor effects with some chemotherapy drugs in vitro.This study evaluated the efficacy and safety of fulvestrant with vinorelbine in patients with hormone receptor positive(HR+)/human epidermal growth factor receptor-2-negative(HER2−)recurrent or metastatic breast cancer.Methods:Patients were intramuscularly administered fulvestrant 500 mg(day 1 per cycle for 28 days)and oral vinorelbine(60 mg/m2 on days 1,8,and 15 of each cycle).The primary endpoint was progression-free survival(PFS).Secondary endpoints included overall survival,objective response rate,disease control rate,duration of response,and safety.Results:A total of 38 patients with HR+/HER2−advanced breast cancer included in the study were followed up for a median time of 25.1 months.The overall median PFS was 9.86 months[95%confidence interval(CI)7.2-23.13],and the median PFS of the first-line and the second-line treatment population was 20.73 months(95%CI 9.82 to NR)and 4.27 months(95%CI 3.68 to NR),respectively.Most adverse events reported were of grade 1/2,and none were of grade 4/5.Conclusions:This is the first exploratory study of a fulvestrant and oral vinorelbine regimen in the treatment of HR+/HER2−recurrent and metastatic breast cancer.The combination chemo-endocrine therapy was efficacious,safe,and promising for patients with HR+/HER2−advanced breast cancer.展开更多
Objective:Mammographic calcifications are a common feature of breast cancer,but their molecular characteristics and treatment implications in hormone receptor-positive(HR+)/human epidermal growth factor receptor 2-neg...Objective:Mammographic calcifications are a common feature of breast cancer,but their molecular characteristics and treatment implications in hormone receptor-positive(HR+)/human epidermal growth factor receptor 2-negative(HER2−)breast cancer remain unclear.Methods:We retrospectively collected mammography records of an HR+/HER2−breast cancer cohort(n=316)with matched clinicopathological,genomic,transcriptomic,and metabolomic data.On the basis of mammographic images,we grouped tumors by calcification status into calcification-negative tumors,tumors with probably benign calcifications,tumors with calcification of lowmoderate suspicion for maligancy and tumors with calcification of high suspicion for maligancy.We then explored the molecular characteristics associated with each calcification status across multiple dimensions.Results:Among the different statuses,tumors with probably benign calcifications exhibited elevated hormone receptor immunohistochemical staining scores,estrogen receptor(ER)pathway activation,lipid metabolism,and sensitivity to endocrine therapy.Tumors with calcifications of high suspicion for malignancy had relatively larger tumor sizes,elevated lymph node metastasis incidence,Ki-67 staining scores,genomic instability,cell cycle pathway activation,and may benefit from cyclin-dependent kinase 4 and 6(CDK4/6)inhibitors.Conclusions:Our research established links between tumor calcifications and molecular features,thus proposing potential precision treatment strategies for HR+/HER2−breast cancer.展开更多
目的探讨雄激素受体(androgen receptor,AR)在HER-2+(HR-),HER-2+(HR+)及三阴性(triplenegative breast cancer,TNBC)乳腺癌中的表达及其与临床病理特征的关系。方法收集2014年5月至2017年4月手术切除的260例HER-2+(HR+),HER-2+(HR-)和...目的探讨雄激素受体(androgen receptor,AR)在HER-2+(HR-),HER-2+(HR+)及三阴性(triplenegative breast cancer,TNBC)乳腺癌中的表达及其与临床病理特征的关系。方法收集2014年5月至2017年4月手术切除的260例HER-2+(HR+),HER-2+(HR-)和三阴性乳腺癌标本,采用免疫组织化学方法检测AR的表达情况,采用χ~2检验分析AR在三个分型中的表达特点及其与临床病理特征的关系,采用Kaplan-Meier生存分析曲线显示AR在三个分型乳腺癌患者中的预后价值。结果AR的表达与组织分级、组织学类型、组织是否存在坏死相关(P<0.05),与ER、PR、HER-2、p53的表达有密切联系(P<0.01)。AR在HER-2+(HR-),HER-2+(HR+)和三阴性乳腺癌中的表达率分别为85.71%(66/77),74.03%(57/77)和29.25%(31/106),三组间的差异具有统计学意义(P<0.01)。生存曲线显示,AR阳性无病生存率高于AR阴性(P<0.05),AR阳性和AR阴性总生存率差异无统计学意义。结论AR的表达与HER-2+(HR-),HER-2+(HR+)及三阴性乳腺癌患者的组织分级、组织学类型、组织坏死以及预后等临床病理参数具有较好的相关性。展开更多
基金supported by grants from the National Key R&D Program of China(Grant No.2018YFC0115204)the National Natural Science Foundation of China(Grant No.81672634)+3 种基金the Chinese Society of Clinical Oncology Foundation(Grant No.Y-2019AZMS-0377)the Beijing Medical Award Foundation(Grant No.YXJL-2020-0941-0763)Beijing Hope Run Special Fund of Cancer Foundation of China(Grant No.LC2019B16)Beijing Xisike Clinical Oncology Research Foundation(Grant No.Y-pirrefabre202101-0008).
文摘Objective:Endocrine therapy with fulvestrant has shown synergistic antitumor effects with some chemotherapy drugs in vitro.This study evaluated the efficacy and safety of fulvestrant with vinorelbine in patients with hormone receptor positive(HR+)/human epidermal growth factor receptor-2-negative(HER2−)recurrent or metastatic breast cancer.Methods:Patients were intramuscularly administered fulvestrant 500 mg(day 1 per cycle for 28 days)and oral vinorelbine(60 mg/m2 on days 1,8,and 15 of each cycle).The primary endpoint was progression-free survival(PFS).Secondary endpoints included overall survival,objective response rate,disease control rate,duration of response,and safety.Results:A total of 38 patients with HR+/HER2−advanced breast cancer included in the study were followed up for a median time of 25.1 months.The overall median PFS was 9.86 months[95%confidence interval(CI)7.2-23.13],and the median PFS of the first-line and the second-line treatment population was 20.73 months(95%CI 9.82 to NR)and 4.27 months(95%CI 3.68 to NR),respectively.Most adverse events reported were of grade 1/2,and none were of grade 4/5.Conclusions:This is the first exploratory study of a fulvestrant and oral vinorelbine regimen in the treatment of HR+/HER2−recurrent and metastatic breast cancer.The combination chemo-endocrine therapy was efficacious,safe,and promising for patients with HR+/HER2−advanced breast cancer.
基金supported by grants from the National Key Research and Development Project of China(Grant No.2020YFA0112304)the National Natural Science Foundation of China(Grant Nos.81922048,82072922,91959207,and 92159301)+3 种基金the Program of Shanghai Academic/Technology Research Leader(Grant No.20XD1421100)the Shanghai Key Laboratory of Breast Cancer(Grant No.12DZ2260100)the Clinical Research Plan of SHDC(Grant Nos.SHDC2020CR4002 and SHDC2020CR5005)the SHDC Municipal Project for Developing Emerging and Frontier Technology in Shanghai Hospitals(Grant No.SHDC12021103).
文摘Objective:Mammographic calcifications are a common feature of breast cancer,but their molecular characteristics and treatment implications in hormone receptor-positive(HR+)/human epidermal growth factor receptor 2-negative(HER2−)breast cancer remain unclear.Methods:We retrospectively collected mammography records of an HR+/HER2−breast cancer cohort(n=316)with matched clinicopathological,genomic,transcriptomic,and metabolomic data.On the basis of mammographic images,we grouped tumors by calcification status into calcification-negative tumors,tumors with probably benign calcifications,tumors with calcification of lowmoderate suspicion for maligancy and tumors with calcification of high suspicion for maligancy.We then explored the molecular characteristics associated with each calcification status across multiple dimensions.Results:Among the different statuses,tumors with probably benign calcifications exhibited elevated hormone receptor immunohistochemical staining scores,estrogen receptor(ER)pathway activation,lipid metabolism,and sensitivity to endocrine therapy.Tumors with calcifications of high suspicion for malignancy had relatively larger tumor sizes,elevated lymph node metastasis incidence,Ki-67 staining scores,genomic instability,cell cycle pathway activation,and may benefit from cyclin-dependent kinase 4 and 6(CDK4/6)inhibitors.Conclusions:Our research established links between tumor calcifications and molecular features,thus proposing potential precision treatment strategies for HR+/HER2−breast cancer.
文摘目的探讨雄激素受体(androgen receptor,AR)在HER-2+(HR-),HER-2+(HR+)及三阴性(triplenegative breast cancer,TNBC)乳腺癌中的表达及其与临床病理特征的关系。方法收集2014年5月至2017年4月手术切除的260例HER-2+(HR+),HER-2+(HR-)和三阴性乳腺癌标本,采用免疫组织化学方法检测AR的表达情况,采用χ~2检验分析AR在三个分型中的表达特点及其与临床病理特征的关系,采用Kaplan-Meier生存分析曲线显示AR在三个分型乳腺癌患者中的预后价值。结果AR的表达与组织分级、组织学类型、组织是否存在坏死相关(P<0.05),与ER、PR、HER-2、p53的表达有密切联系(P<0.01)。AR在HER-2+(HR-),HER-2+(HR+)和三阴性乳腺癌中的表达率分别为85.71%(66/77),74.03%(57/77)和29.25%(31/106),三组间的差异具有统计学意义(P<0.01)。生存曲线显示,AR阳性无病生存率高于AR阴性(P<0.05),AR阳性和AR阴性总生存率差异无统计学意义。结论AR的表达与HER-2+(HR-),HER-2+(HR+)及三阴性乳腺癌患者的组织分级、组织学类型、组织坏死以及预后等临床病理参数具有较好的相关性。
