Pub Date : 2021-02-15DOI: 10.1158/1538-7445.SABCS20-PS5-46
E. Torlakovic, S. R. Sompuram, K. Vani, Lili Wang, Anika K Schaedle, P. DeRose, S. Bogen
: Traceability of measurement to a higher order reference standard is a foundation of laboratory testing. There is as yet no method for creating reference standards for cellular proteins in situ in an analogous fashion as for soluble analytes. At present, IHC laboratories produce results for breast cancer hormone receptors without connection to a reference standard. Not surprisingly, high rates of testing variation as well as discrepancies among IHC laboratories have been reported. To address this need, we developed a system of measurement traceability using a linked fluorescein tag for creating reference standards for any cellular analyte and, as a first test, validate it for estrogen receptor (ER) testing. In this study, the newly developed ER standard defines and compares the thresholds separating “high positive”, “low positive”, and “negative” tests according to updated ASCO/CAP guidelines as detected by clinical IHC laboratories in a national external quality assessment survey. This reference standard utilizes NIST Standard Reference Material (SRM) 1934 as a universal IHC standard. We calculated ER concentration based on a linked fluorescence measurement traceable to NIST SRM 1934 as each ER is linked to
{"title":"Abstract PS5-46: Introduction and clinical validation of metrology standards for immunohistochemistry (IHC); New tool for standardization of estrogen receptor (ER) IHC assay in breast cancer","authors":"E. Torlakovic, S. R. Sompuram, K. Vani, Lili Wang, Anika K Schaedle, P. DeRose, S. Bogen","doi":"10.1158/1538-7445.SABCS20-PS5-46","DOIUrl":"https://doi.org/10.1158/1538-7445.SABCS20-PS5-46","url":null,"abstract":": Traceability of measurement to a higher order reference standard is a foundation of laboratory testing. There is as yet no method for creating reference standards for cellular proteins in situ in an analogous fashion as for soluble analytes. At present, IHC laboratories produce results for breast cancer hormone receptors without connection to a reference standard. Not surprisingly, high rates of testing variation as well as discrepancies among IHC laboratories have been reported. To address this need, we developed a system of measurement traceability using a linked fluorescein tag for creating reference standards for any cellular analyte and, as a first test, validate it for estrogen receptor (ER) testing. In this study, the newly developed ER standard defines and compares the thresholds separating “high positive”, “low positive”, and “negative” tests according to updated ASCO/CAP guidelines as detected by clinical IHC laboratories in a national external quality assessment survey. This reference standard utilizes NIST Standard Reference Material (SRM) 1934 as a universal IHC standard. We calculated ER concentration based on a linked fluorescence measurement traceable to NIST SRM 1934 as each ER is linked to","PeriodicalId":20307,"journal":{"name":"Poster Session Abstracts","volume":"49 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87986305","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-02-15DOI: 10.1158/1538-7445.SABCS20-PS14-01
R. Coleman, G. Fried, Sung-Bae Kim, I. Kuchuk, D. Kiesl, M. Ramos, J. Sohn, J. Siegel, Rui Li, D. Uema, V. Wagner, H. Rugo
Background: Approximately 65-75% of women with metastatic breast cancer (mBC) have skeletal involvement, which can result in bone pain, pathologic fractures, and spinal-cord compression (SCC), impairing quality of life and function. Radium-223 dichloride (Ra-223) is a targeted alpha-emitting radionucleotide therapy that is approved for treatment of bone metastases from castration-resistant prostate cancer, but has been little studied in mBC. Objective: To assess the efficacy and safety of Ra-223 in women with bone-metastatic hormone receptor (HR)-positive breast cancer receiving endocrine monotherapy. Methods: This international, phase 2, randomized, double-blind, placebo-controlled trial (NCT02258464) involved women ≥18 years with HER2-negative, HR-positive, bone-dominant (≥2 skeletal lesions) mBC. Women with 1-2 skeletal-related events before study entry, treated with ≥1 line of hormonal therapy in the metastatic setting and bone-supportive agents, were randomized 1:1 to receive Ra-223 55 kBq/kg or placebo intravenously every 4 weeks for up to 6 cycles, combined with local standard of practice endocrine monotherapy and bone-targeted therapy with denosumab or a bisphosphonate. The primary endpoint was symptomatic skeletal event-free survival (SSE-FS). SSE was defined as external beam radiotherapy to relieve skeletal symptoms, symptomatic pathologic fractures, SCC, cancer-related orthopedic surgery, or death from any cause. Secondary endpoints included overall survival (OS), radiologic progression-free survival (rPFS), pain measurements, and safety. Results: Considering the evolving treatment landscape and slow recruitment, enrollment was closed early, and patients who completed treatment were permitted to roll over early to a follow-up study. Of the planned 227 women, 99 were randomized (Ra-223 n=49, placebo n=50; median age 57 years, range 28-85 years; 89% postmenopausal). The median number of injections received was 6 (range 1-6) in both arms. Median SSE-FS was 30 months (80% confidence interval [CI] 22, 43) in the Ra-223 arm vs 18 months (80% CI 9, 28) in the placebo arm; hazard ratio 0.75 (95% CI 0.41, 1.36; P=0.334). Trends in favor of Ra-223 over placebo were found for OS and pain measurements (Table). Treatment-emergent adverse events (TEAEs) occurred in 96% of patients in the Ra-223 arm and 94% in the placebo arm; drug-related TEAEs occurred in 44% and 33% of patients, respectively, and grade 3/4 TEAEs in 31% and 39%, respectively. In the Ra-223 vs placebo arms, there were fewer serious TEAEs (6% vs 25%, respectively, most commonly bone pain), bone-associated TEAEs (21% vs 27%, respectively; fracture 4% vs 12%, respectively), and TEAEs leading to treatment discontinuation (2% vs 6%, respectively). Conclusion: Although the primary endpoint was not met, possibly because of the small sample size, early discontinuation of follow-up, and lower than anticipated event rates, numerical trends consistently favored Ra-223 over placebo for SSE-FS,
背景:大约65-75%的女性转移性乳腺癌(mBC)有骨骼受累，可导致骨痛、病理性骨折和脊髓压迫(SCC)，影响生活质量和功能。镭-223二氯化(Ra-223)是一种靶向α -放射核苷酸疗法，被批准用于治疗去势抵抗性前列腺癌的骨转移，但在mBC的研究很少。目的:评价Ra-223在骨转移激素受体(HR)阳性乳腺癌患者接受内分泌单药治疗中的疗效和安全性。方法:这项国际2期、随机、双盲、安慰剂对照试验(NCT02258464)涉及年龄≥18岁、her2阴性、hr阳性、骨显性(≥2个骨骼病变)mBC的女性。在研究开始前有1-2个骨骼相关事件的妇女，在转移情况下接受≥1线激素治疗和骨支持药物治疗，随机1:1接受Ra-223 55 kBq/kg或安慰剂静脉注射，每4周最多6个周期，结合当地标准的内分泌单药治疗和denosumab或双膦酸盐骨靶向治疗。主要终点是症状性骨骼无事件生存期(SSE-FS)。SSE被定义为用于缓解骨骼症状、症状性病理性骨折、SCC、癌症相关骨科手术或任何原因导致的死亡的外束放疗。次要终点包括总生存期(OS)、放射学无进展生存期(rPFS)、疼痛测量和安全性。结果:考虑到不断变化的治疗环境和缓慢的招募，登记提前关闭，完成治疗的患者被允许提前转入随访研究。在计划的227名妇女中，99名被随机分配(Ra-223 n=49，安慰剂n=50;年龄中位数57岁，范围28-85岁;89%的绝经后)。双臂接受注射的中位数为6次(范围1-6)。Ra-223组的中位SSE-FS为30个月(80%可信区间[CI] 22,43)，而安慰剂组为18个月(80%可信区间[CI] 9,28);风险比0.75 (95% CI 0.41, 1.36;P = 0.334)。在OS和疼痛测量中发现Ra-223优于安慰剂的趋势(表)。在Ra-223组中，96%的患者发生了治疗后出现的不良事件(teae)，而在安慰剂组中，这一比例为94%;药物相关性teae发生率分别为44%和33%，3/4级teae发生率分别为31%和39%。在Ra-223组和安慰剂组中，严重teae(分别为6%和25%，最常见的是骨痛)、骨相关teae(分别为21%和27%;骨折(分别为4%和12%)和teae导致治疗中断(分别为2%和6%)。结论:虽然没有达到主要终点，可能是由于样本量小、早期终止随访和低于预期的事件发生率，但在SSE-FS、OS和骨痛测量方面，Ra-223的数值趋势始终优于安慰剂。两组的总体TEAE发生率相似，但Ra-223组的严重或重度TEAE发生率低于安慰剂组。引文格式:Robert E. Coleman, Georgeta Fried, Sung-Bae Kim, Iryna Kuchuk, David Kiesl, Manuel Ramos, jooohyuk Sohn, Jonathan Siegel, Rui Li, Deise Uema, Volker Wagner, Hope S. Rugo镭-223在接受内分泌治疗的hr阳性骨转移性乳腺癌患者中的作用:国际2期随机、双盲、安慰剂对照试验[摘要]。参见:2020年圣安东尼奥乳腺癌虚拟研讨会论文集;2020年12月8-11日;费城(PA): AACR;癌症杂志，2021;81(4增刊):PS14-01。
{"title":"Abstract PS14-01: Radium-223 in women with HR-positive bone-metastatic breast cancer receiving endocrine therapy: International phase 2, randomized, double-blind, placebo-controlled trial","authors":"R. Coleman, G. Fried, Sung-Bae Kim, I. Kuchuk, D. Kiesl, M. Ramos, J. Sohn, J. Siegel, Rui Li, D. Uema, V. Wagner, H. Rugo","doi":"10.1158/1538-7445.SABCS20-PS14-01","DOIUrl":"https://doi.org/10.1158/1538-7445.SABCS20-PS14-01","url":null,"abstract":"Background: Approximately 65-75% of women with metastatic breast cancer (mBC) have skeletal involvement, which can result in bone pain, pathologic fractures, and spinal-cord compression (SCC), impairing quality of life and function. Radium-223 dichloride (Ra-223) is a targeted alpha-emitting radionucleotide therapy that is approved for treatment of bone metastases from castration-resistant prostate cancer, but has been little studied in mBC. Objective: To assess the efficacy and safety of Ra-223 in women with bone-metastatic hormone receptor (HR)-positive breast cancer receiving endocrine monotherapy. Methods: This international, phase 2, randomized, double-blind, placebo-controlled trial (NCT02258464) involved women ≥18 years with HER2-negative, HR-positive, bone-dominant (≥2 skeletal lesions) mBC. Women with 1-2 skeletal-related events before study entry, treated with ≥1 line of hormonal therapy in the metastatic setting and bone-supportive agents, were randomized 1:1 to receive Ra-223 55 kBq/kg or placebo intravenously every 4 weeks for up to 6 cycles, combined with local standard of practice endocrine monotherapy and bone-targeted therapy with denosumab or a bisphosphonate. The primary endpoint was symptomatic skeletal event-free survival (SSE-FS). SSE was defined as external beam radiotherapy to relieve skeletal symptoms, symptomatic pathologic fractures, SCC, cancer-related orthopedic surgery, or death from any cause. Secondary endpoints included overall survival (OS), radiologic progression-free survival (rPFS), pain measurements, and safety. Results: Considering the evolving treatment landscape and slow recruitment, enrollment was closed early, and patients who completed treatment were permitted to roll over early to a follow-up study. Of the planned 227 women, 99 were randomized (Ra-223 n=49, placebo n=50; median age 57 years, range 28-85 years; 89% postmenopausal). The median number of injections received was 6 (range 1-6) in both arms. Median SSE-FS was 30 months (80% confidence interval [CI] 22, 43) in the Ra-223 arm vs 18 months (80% CI 9, 28) in the placebo arm; hazard ratio 0.75 (95% CI 0.41, 1.36; P=0.334). Trends in favor of Ra-223 over placebo were found for OS and pain measurements (Table). Treatment-emergent adverse events (TEAEs) occurred in 96% of patients in the Ra-223 arm and 94% in the placebo arm; drug-related TEAEs occurred in 44% and 33% of patients, respectively, and grade 3/4 TEAEs in 31% and 39%, respectively. In the Ra-223 vs placebo arms, there were fewer serious TEAEs (6% vs 25%, respectively, most commonly bone pain), bone-associated TEAEs (21% vs 27%, respectively; fracture 4% vs 12%, respectively), and TEAEs leading to treatment discontinuation (2% vs 6%, respectively). Conclusion: Although the primary endpoint was not met, possibly because of the small sample size, early discontinuation of follow-up, and lower than anticipated event rates, numerical trends consistently favored Ra-223 over placebo for SSE-FS, ","PeriodicalId":20307,"journal":{"name":"Poster Session Abstracts","volume":"71 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74368736","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-02-15DOI: 10.1158/1538-7445.SABCS20-PS10-50
Joanna Kufel-Grabowska, T. San, A. Bernardo, L. Cavanna, I. Pérez, G. Suchodolska, J. Hippenmeyer, P. Gokani, M. Lillie, C. Rodríguez
Background: Over recent years, therapeutic biosimilars have started to be licensed as oncology treatments in both palliative and potentially curative settings, but little is known about their uptake and usage in routine clinical practice. ABP 980 is a trastuzumab biosimilar that is licensed in Europe and the USA for the treatment of HER2+ early or metastatic breast cancer and metastatic gastric cancer. This European real-world study aimed to describe patterns of ABP 980 usage in clinical practice in patients with breast cancer. Methods: This descriptive observational chart review study included consecutive patients aged ≥18 years with HER2+ breast cancer (any disease stage or treatment phase) who were receiving or had previously received ABP 980 and had medical charts available for data extraction. Patients were followed up from ABP 980 initiation to withdrawal of consent, death, loss to follow up, entry into an interventional trial, or study end (12 months after last patient enrolled). Follow-up data from ABP 980 initiation to enrolment were retrospectively collected; data after enrolment were prospectively collected. Data were extracted into electronic case report forms quarterly. The primary objective is to describe patient demographics and disease characteristics by treatment phase and prior trastuzumab exposure and communication with patients about biosimilar use is an exploratory objective. Other exploratory endpoints are ABP 980 safety (including cardiac dysfunction, infusion-related reactions and other adverse events of interest) and efficacy (both to be assessed in the final analysis). This planned interim analysis was performed approximately 6 months after the first patient enrolled and provides baseline data on patient characteristics. Results: At the time of analysis, 135 women were included from five countries (Poland n=42; Italy n=38; the Netherlands n=32; France n=21; Spain n=2). Patients were mostly recruited from hospital-based sites (61%), including a mixture of academic/non-academic and publicly/privately funded centers. A policy on biosimilar use was documented in 28% of sites and 36% of patients were informed they were starting a biosimilar, with the brand mentioned to 34% of patients. Mean (standard deviation [SD]) age at ABP 980 initiation was 58.3 (11.5) years and mean (SD) time from ABP 980 initiation to enrolment was 7.3 (4.8) months. At ABP 980 initiation, 22%, 27%, 13% and 28% of patients had Stage I, II, III or IV disease, respectively. Overall, 68% of patients had estrogen/progesterone receptor-positive tumors and all patients with known ECOG performance status (n=73) had a score of 0 or 1. ABP 980 usage was approximately equally distributed across neoadjuvant (39%), adjuvant (30%), and metastatic settings (30%). Of the patients receiving treatment for metastatic disease (n=41), most received ABP 980 as their 1st- (56%) or 2nd- (20%) line treatment. Overall, 40% of patients had switched to ABP 980 from another trastu
背景:近年来，治疗性生物仿制药已开始获准作为姑息治疗和潜在治疗的肿瘤治疗药物，但对其在常规临床实践中的吸收和使用知之甚少。ABP 980是一种曲妥珠单抗生物仿制药，已在欧洲和美国获得许可，用于治疗HER2+早期或转移性乳腺癌和转移性胃癌。这项欧洲真实世界的研究旨在描述ABP 980在乳腺癌患者临床实践中的使用模式。方法:这项描述性观察图回顾研究纳入了年龄≥18岁的HER2+乳腺癌患者(任何疾病阶段或治疗阶段)，这些患者正在接受或曾经接受过ABP 980治疗，并有可用于数据提取的医学图表。患者从ABP 980开始随访到撤回同意、死亡、失去随访、进入介入性试验或研究结束(最后一名患者入组后12个月)。回顾性收集了从ABP 980开始到入组的随访数据;前瞻性地收集入组后的数据。数据每季度被提取到电子病例报告表格中。主要目标是通过治疗阶段和曲妥珠单抗暴露来描述患者的人口统计学和疾病特征，并与患者就生物仿制药的使用进行沟通是一个探索性目标。其他探索性终点是ABP 980的安全性(包括心功能障碍、输注相关反应和其他相关不良事件)和疗效(两者都将在最终分析中进行评估)。该计划的中期分析在第一个患者入组后大约6个月进行，并提供患者特征的基线数据。结果:在分析时，135名妇女来自5个国家(波兰n=42;意大利n = 38岁;荷兰n=32;法国n = 21;西班牙n = 2)。患者大多来自医院(61%)，包括学术/非学术和公共/私人资助的中心。28%的网站记录了生物仿制药的使用政策，36%的患者被告知他们正在开始使用生物仿制药，34%的患者提到了该品牌。ABP 980起始时的平均(标准差[SD])年龄为58.3(11.5)岁，从ABP 980起始到入组的平均(SD)时间为7.3(4.8)个月。在ABP 980起始时，分别有22%、27%、13%和28%的患者为I、II、III或IV期疾病。总体而言，68%的患者患有雌激素/孕激素受体阳性肿瘤，所有已知ECOG表现状态的患者(n=73)得分为0或1。ABP 980的使用在新辅助治疗(39%)、辅助治疗(30%)和转移治疗(30%)中大致均匀分布。在接受转移性疾病治疗的患者中(n=41)，大多数接受ABP 980作为一线(56%)或二线(20%)治疗。总体而言，40%的患者从另一种曲妥珠单抗产品转向ABP 980。在这54名患者中，44%的患者从静脉曲妥珠单抗转为静脉曲妥珠单抗，15%的患者从皮下曲妥珠单抗转为静脉曲妥珠单抗。大多数从皮下起始曲妥珠单抗转向ABP 980的患者正在接受转移性疾病的治疗(7/8)。结论:这些中期结果报告了曲妥珠单抗生物类似药ABP 980在欧洲的使用模式。在各种机构类型和乳腺癌治疗环境中，包括那些具有治愈潜力的治疗环境中，有40%的患者从另一种曲妥珠单抗产品转向ABP 980。本研究的招募工作正在进行中。引文格式:Joanna Kufel-Grabowska, Tevy San, Antonio Bernardo, Luigi Cavanna, Isaura Fernandez Perez, Grazyna Suchodolska, Jane Hippenmeyer, Priya Gokani, Mark Lillie, Cesar A. Rodriguez。曲妥珠单抗生物类似药(ABP 980)在欧洲HER2+乳腺癌患者临床治疗中的使用模式:一项观察图回顾研究(GARDENIA)的中期分析[摘要]。参见:2020年圣安东尼奥乳腺癌虚拟研讨会论文集;2020年12月8-11日;费城(PA): AACR;癌症杂志，2021;81(4增刊):摘要nr PS10-50。
{"title":"Abstract PS10-50: Patterns of use of a trastuzumab biosimilar (ABP 980) in patients with HER2+ breast cancer treated in clinical practice in Europe: An interim analysis from an observational chart review study (GARDENIA)","authors":"Joanna Kufel-Grabowska, T. San, A. Bernardo, L. Cavanna, I. Pérez, G. Suchodolska, J. Hippenmeyer, P. Gokani, M. Lillie, C. Rodríguez","doi":"10.1158/1538-7445.SABCS20-PS10-50","DOIUrl":"https://doi.org/10.1158/1538-7445.SABCS20-PS10-50","url":null,"abstract":"Background: Over recent years, therapeutic biosimilars have started to be licensed as oncology treatments in both palliative and potentially curative settings, but little is known about their uptake and usage in routine clinical practice. ABP 980 is a trastuzumab biosimilar that is licensed in Europe and the USA for the treatment of HER2+ early or metastatic breast cancer and metastatic gastric cancer. This European real-world study aimed to describe patterns of ABP 980 usage in clinical practice in patients with breast cancer. Methods: This descriptive observational chart review study included consecutive patients aged ≥18 years with HER2+ breast cancer (any disease stage or treatment phase) who were receiving or had previously received ABP 980 and had medical charts available for data extraction. Patients were followed up from ABP 980 initiation to withdrawal of consent, death, loss to follow up, entry into an interventional trial, or study end (12 months after last patient enrolled). Follow-up data from ABP 980 initiation to enrolment were retrospectively collected; data after enrolment were prospectively collected. Data were extracted into electronic case report forms quarterly. The primary objective is to describe patient demographics and disease characteristics by treatment phase and prior trastuzumab exposure and communication with patients about biosimilar use is an exploratory objective. Other exploratory endpoints are ABP 980 safety (including cardiac dysfunction, infusion-related reactions and other adverse events of interest) and efficacy (both to be assessed in the final analysis). This planned interim analysis was performed approximately 6 months after the first patient enrolled and provides baseline data on patient characteristics. Results: At the time of analysis, 135 women were included from five countries (Poland n=42; Italy n=38; the Netherlands n=32; France n=21; Spain n=2). Patients were mostly recruited from hospital-based sites (61%), including a mixture of academic/non-academic and publicly/privately funded centers. A policy on biosimilar use was documented in 28% of sites and 36% of patients were informed they were starting a biosimilar, with the brand mentioned to 34% of patients. Mean (standard deviation [SD]) age at ABP 980 initiation was 58.3 (11.5) years and mean (SD) time from ABP 980 initiation to enrolment was 7.3 (4.8) months. At ABP 980 initiation, 22%, 27%, 13% and 28% of patients had Stage I, II, III or IV disease, respectively. Overall, 68% of patients had estrogen/progesterone receptor-positive tumors and all patients with known ECOG performance status (n=73) had a score of 0 or 1. ABP 980 usage was approximately equally distributed across neoadjuvant (39%), adjuvant (30%), and metastatic settings (30%). Of the patients receiving treatment for metastatic disease (n=41), most received ABP 980 as their 1st- (56%) or 2nd- (20%) line treatment. Overall, 40% of patients had switched to ABP 980 from another trastu","PeriodicalId":20307,"journal":{"name":"Poster Session Abstracts","volume":"72 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75643690","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-02-15DOI: 10.1158/1538-7445.sabcs20-ps1-32
A. Goyal, Shama Puri, A. Marshall, K. Valassiadou, M. Hoosein, A. Carmichael, Gabriella Erdelyi, Nitasha Sharma, J. Dunn, J. York
{"title":"Abstract PS1-32: A multicentre prospective feasibility study of carbon dye tattooing of biopsied axillary node and surgical localisation in breast cancer patients","authors":"A. Goyal, Shama Puri, A. Marshall, K. Valassiadou, M. Hoosein, A. Carmichael, Gabriella Erdelyi, Nitasha Sharma, J. Dunn, J. York","doi":"10.1158/1538-7445.sabcs20-ps1-32","DOIUrl":"https://doi.org/10.1158/1538-7445.sabcs20-ps1-32","url":null,"abstract":"","PeriodicalId":20307,"journal":{"name":"Poster Session Abstracts","volume":"48 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74805939","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-02-15DOI: 10.1158/1538-7445.sabcs20-ps11-42
E. Obeid, R. Parikh, E. Esterberg, B. Arondekar, A. Hitchens, L. S. Arruda, A. Niyazov
{"title":"Abstract PS11-42: Treatment patterns and clinical outcomes among patients (pts) with HER2- advanced breast cancer (ABC) and germlineBRCA1/2mutation(s) (gBRCA1/2mut): results from a US real-world study","authors":"E. Obeid, R. Parikh, E. Esterberg, B. Arondekar, A. Hitchens, L. S. Arruda, A. Niyazov","doi":"10.1158/1538-7445.sabcs20-ps11-42","DOIUrl":"https://doi.org/10.1158/1538-7445.sabcs20-ps11-42","url":null,"abstract":"","PeriodicalId":20307,"journal":{"name":"Poster Session Abstracts","volume":"21 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84683491","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-02-15DOI: 10.1158/1538-7445.SABCS20-PS19-04
Darius O Gaymon, M. Lippman, P. Foley, P. Miller
Correct interpretation of disease progression and therapeutic responses in mouse models of breast cancer requires interrogation of models and conditions that faithfully recapitulate human disease and conditions that mimic clinical intervention. Historically, standard temperature (ST) for in vivo murine research has been approximately 70-72°F (21-22°C), mimicking ambient temperatures in laboratories that are comfortable for researchers. However, previous work from the Repasky lab demonstrated that ST housing results in chronic cold stress and immune suppression mediated by an increase in norepinrephrine (NE) levels, leading to increased tumor aggressiveness. In contrast, syngeneic murine mammary tumors in mice housed at higher temperatures [~ 82°F] grew more slowly and resulted in fewer metastases. Based on these findings, we investigated tumor progression and metastasis in a temperature dose response in two syngeneic murine mammary tumor models: the balb/c-4T1 model and the c57bl6/E0771-LMB (a lung metastatic variant of E0771 cells) model.Mice were acclimatized in rooms with three different ambient temperaures and challenged with tumor cells. ST was maintained at 70-72°F, while mid-temperature (MT) was maintained at 78-80°F, and high temperature (HT) was maintained at 84-85°F. Compared to ST and MT, an ambient temperature of 84-85°F resulted in a statistically significant delay in tumor formation and decreased primary tumor growth by unpaired t-test (p=.0006) At day 13, when 4T1 tumors are typically well-initiated and measurable by caliper, mean tumor volumes in the ST-housed mice were significantly larger than the HT group. At day 21, ST tumors means were 4 times larger than HT. In the E0771-LMB model, mean tumor volumes on day 14 were nearly 3 times larger in ST-housed mice than HT. At day 27, the mean tumor volumes were 2 times larger in the ST group compared to HT-housed mice. Data on metastasis will be presented at the meeting. Mean NE levels in mice housed at ST were twice as high as those at HT, providing ancillary evidence that traditional “standard” temperatures are a significant stressor for mice (p=.0091).These data demonstrate the potential for misleading interpretations of biological significance of chronic cold stress when modeling immunocompetent tumor progression [conditions almost universally employed in most studies]. Furthermore, these data demonstrate that the presence of chronic cold stress and its immunosuppressive effects call into question the interpretation of many previous studies completed at or near standard temperature and may suggest the need to increase ambient temperatures in syngeneic experiments in order to more accurately model human disease. Citation Format: Darius O Gaymon, Marc Lippman, Patricia Foley, Philip Miller. Standard temperature husbandry increases tumor aggressiveness via chronic cold stress in murine mammary cancer models [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Sym
正确解释乳腺癌小鼠模型中的疾病进展和治疗反应，需要对忠实地概括人类疾病和模拟临床干预条件的模型和条件进行询问。从历史上看，小鼠体内研究的标准温度(ST)约为70-72°F(21-22°C)，模拟实验室环境温度，使研究人员感到舒适。然而，Repasky实验室先前的工作表明，ST住房导致慢性冷应激和由去甲肾上腺素(NE)水平增加介导的免疫抑制，导致肿瘤侵袭性增加。相比之下，同基因小鼠乳腺肿瘤在较高温度下(~ 82°F)生长更慢，导致更少的转移。基于这些发现，我们研究了两种同基因小鼠乳腺肿瘤模型:balb/c-4T1模型和c57bl6/E0771- lmb (E0771细胞的肺转移变体)模型的肿瘤进展和转移的温度剂量反应。小鼠在三种不同环境温度的房间中适应环境，并接受肿瘤细胞的攻击。温度维持在70-72°F，中温(MT)维持在78-80°F，高温(HT)维持在84-85°F。与ST组和MT组相比，84-85°F的环境温度导致肿瘤形成的延迟和原发肿瘤生长的减少(p=.0006)，通过未配对t检验(p=.0006)。在第13天，当4T1肿瘤典型地启动和用卡尺测量时，ST组小鼠的平均肿瘤体积显著大于HT组。在第21天，ST肿瘤的平均值是HT的4倍。在E0771-LMB模型中，st组小鼠第14天的平均肿瘤体积比HT组大近3倍。在第27天，ST组的平均肿瘤体积比ht组大2倍。有关转移的数据将在会议上公布。在高温条件下饲养的小鼠的平均NE水平是高温条件下的两倍，这提供了辅助证据，表明传统的“标准”温度对小鼠来说是一个重要的应激源(p= 0.0091)。这些数据表明，在模拟免疫活性肿瘤进展(大多数研究中几乎普遍采用的条件)时，可能会对慢性冷应激的生物学意义产生误导性解释。此外，这些数据表明，慢性冷应激的存在及其免疫抑制效应对许多先前在标准温度或接近标准温度下完成的研究的解释提出了质疑，并可能表明需要在同基因实验中提高环境温度，以便更准确地模拟人类疾病。引用格式:Darius O Gaymon, Marc Lippman, Patricia Foley, Philip Miller。标准温度饲养通过慢性冷应激提高小鼠乳腺癌模型的肿瘤侵袭性[摘要]。参见:2020年圣安东尼奥乳腺癌虚拟研讨会论文集;2020年12月8-11日;费城(PA): AACR;癌症杂志，2021;81(4增刊):PS19-04。
{"title":"Abstract PS19-04: Standard temperature husbandry increases tumor aggressiveness via chronic cold stress in murine mammary cancer models","authors":"Darius O Gaymon, M. Lippman, P. Foley, P. Miller","doi":"10.1158/1538-7445.SABCS20-PS19-04","DOIUrl":"https://doi.org/10.1158/1538-7445.SABCS20-PS19-04","url":null,"abstract":"Correct interpretation of disease progression and therapeutic responses in mouse models of breast cancer requires interrogation of models and conditions that faithfully recapitulate human disease and conditions that mimic clinical intervention. Historically, standard temperature (ST) for in vivo murine research has been approximately 70-72°F (21-22°C), mimicking ambient temperatures in laboratories that are comfortable for researchers. However, previous work from the Repasky lab demonstrated that ST housing results in chronic cold stress and immune suppression mediated by an increase in norepinrephrine (NE) levels, leading to increased tumor aggressiveness. In contrast, syngeneic murine mammary tumors in mice housed at higher temperatures [~ 82°F] grew more slowly and resulted in fewer metastases. Based on these findings, we investigated tumor progression and metastasis in a temperature dose response in two syngeneic murine mammary tumor models: the balb/c-4T1 model and the c57bl6/E0771-LMB (a lung metastatic variant of E0771 cells) model.Mice were acclimatized in rooms with three different ambient temperaures and challenged with tumor cells. ST was maintained at 70-72°F, while mid-temperature (MT) was maintained at 78-80°F, and high temperature (HT) was maintained at 84-85°F. Compared to ST and MT, an ambient temperature of 84-85°F resulted in a statistically significant delay in tumor formation and decreased primary tumor growth by unpaired t-test (p=.0006) At day 13, when 4T1 tumors are typically well-initiated and measurable by caliper, mean tumor volumes in the ST-housed mice were significantly larger than the HT group. At day 21, ST tumors means were 4 times larger than HT. In the E0771-LMB model, mean tumor volumes on day 14 were nearly 3 times larger in ST-housed mice than HT. At day 27, the mean tumor volumes were 2 times larger in the ST group compared to HT-housed mice. Data on metastasis will be presented at the meeting. Mean NE levels in mice housed at ST were twice as high as those at HT, providing ancillary evidence that traditional “standard” temperatures are a significant stressor for mice (p=.0091).These data demonstrate the potential for misleading interpretations of biological significance of chronic cold stress when modeling immunocompetent tumor progression [conditions almost universally employed in most studies]. Furthermore, these data demonstrate that the presence of chronic cold stress and its immunosuppressive effects call into question the interpretation of many previous studies completed at or near standard temperature and may suggest the need to increase ambient temperatures in syngeneic experiments in order to more accurately model human disease. Citation Format: Darius O Gaymon, Marc Lippman, Patricia Foley, Philip Miller. Standard temperature husbandry increases tumor aggressiveness via chronic cold stress in murine mammary cancer models [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Sym","PeriodicalId":20307,"journal":{"name":"Poster Session Abstracts","volume":"131 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85636980","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-02-15DOI: 10.1158/1538-7445.sabcs20-ps18-32
A. Nagalingam, N. Muniraj, S. Siddharth, D. Avtanski, S. Parida, Pajamurthy Kuppusamy, N. Saxena
{"title":"Abstract PS18-32: Hyperleptinemia in obese state renders luminal breast cancers refractory to tamoxifen coordinating a crosstalk between Med1, miR205 and Erb B kinases","authors":"A. Nagalingam, N. Muniraj, S. Siddharth, D. Avtanski, S. Parida, Pajamurthy Kuppusamy, N. Saxena","doi":"10.1158/1538-7445.sabcs20-ps18-32","DOIUrl":"https://doi.org/10.1158/1538-7445.sabcs20-ps18-32","url":null,"abstract":"","PeriodicalId":20307,"journal":{"name":"Poster Session Abstracts","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90333300","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2020-08-28DOI: 10.21203/rs.3.rs-66195/v1
Junnnan Xu, T. Sun
Background: Ovarian function suppression is being widely utilized as endocrine therapy to reduce estrogen release in premenopausal breast cancer patients and was achieved either by medical treatment with bilateral oophorectomy, irradiation, or the Gonadotropin releasing hormone (GnRH) agonist. This study aimed to examine whether GnRHa differed from ovarian ablation on depression, sexual dysfunction and quality of life.Methods: The premenopausal breast cancer patients who received ovarian function suppression were enrolled from seven hospital between June 2019 and June 2020. Our independent variable was the type of ovarian suppression, categorized as Ovarian Ablation (OA cohort, n=174) and medical GnRH agonist (GnRHa cohort, n=389). The self-administered questionnaire (OFS-Q5) was developed and used in this study aimed to assess the depression (PHQ-9), sexual dysfunction (FSFI) and quality of life (EORTC QLQ-BR23).Results: In this cross-sectional study, 563 patients with ovarian function suppression completed surveys were collected. The mean sum score of the PHQ-9 tend to be slight decrease in GnRHa cohort than that in ovarian ablation (OA) cohort (11.4 ±5.7 vs. 12.8 ±5.8, OR=1.910, P=0.079). Patients with major depression (PHQ-9≧15) was indicated significantly fewer in GnRHa cohort (31.1% vs 40.2%, P=0.025). The more surprising correlation is less patients with sexual dysfunction (61.5%, FSFI< 23) in OA cohort, a remarkable increase in GnRHa cohort (72.2%, P = 0.011). The ratio of sexual dysfunction remained lower for ovarian ablation women in long-term ovarian suppression (duration of ovarian suppression > 2 years: OA vs GnRHa, OR=1.555, P=0.037). No significantly difference for most subscales of QLQ-BR23 between two cohorts was evident.Conclusions: Our current investigation demonstrate here for the first time that medical GnRHa resulted in favour depression, worse sexual function than those with ovarian ablation, with similar quality of life. This new understanding should help to improve and alleviate adverse effect in patients with diverse ovarian function suppression.
背景:卵巢功能抑制被广泛应用于绝经前乳腺癌患者的内分泌治疗，以减少雌激素的释放，并通过双侧卵巢切除术、照射或促性腺激素释放激素(GnRH)激动剂等药物治疗来实现。本研究旨在探讨GnRHa与卵巢消融术在抑郁、性功能障碍和生活质量方面是否存在差异。方法:选取2019年6月至2020年6月在7家医院接受卵巢功能抑制治疗的绝经前乳腺癌患者。我们的自变量是卵巢抑制的类型，分为卵巢消融术(OA队列，n=174)和药物GnRH激动剂(GnRHa队列，n=389)。本研究采用自填问卷(OFS-Q5)评估抑郁症(PHQ-9)、性功能障碍(FSFI)和生活质量(EORTC QLQ-BR23)。结果:本横断面研究共收集563例卵巢功能抑制患者完成问卷调查。GnRHa组PHQ-9平均总分较OA组略有下降(11.4±5.7比12.8±5.8,OR=1.910, P=0.079)。重度抑郁症(PHQ-9≧15)患者在GnRHa组中明显减少(31.1% vs 40.2%， P=0.025)。更令人惊讶的相关性是OA队列中出现性功能障碍的患者较少(61.5%，FSFI< 23)，而GnRHa队列中出现性功能障碍的患者显著增加(72.2%，P = 0.011)。长期卵巢抑制的卵巢消融女性的性功能障碍比例仍然较低(卵巢抑制持续时间:OA vs GnRHa, OR=1.555, P=0.037)。QLQ-BR23大部分分量表在两组间无显著差异。结论:我们目前的研究首次表明，与卵巢消融术相比，医学GnRHa导致抑郁，性功能更差，但生活质量相似。这一新认识将有助于改善和减轻多种卵巢功能抑制患者的不良反应。
{"title":"Abstract PS9-48: Depression, sexual dysfunction and quality of life among breast cancer patients with ovarian function suppression: A cross sectional study between ovarian ablation verse GnRH agonists","authors":"Junnnan Xu, T. Sun","doi":"10.21203/rs.3.rs-66195/v1","DOIUrl":"https://doi.org/10.21203/rs.3.rs-66195/v1","url":null,"abstract":"\u0000 Background: Ovarian function suppression is being widely utilized as endocrine therapy to reduce estrogen release in premenopausal breast cancer patients and was achieved either by medical treatment with bilateral oophorectomy, irradiation, or the Gonadotropin releasing hormone (GnRH) agonist. This study aimed to examine whether GnRHa differed from ovarian ablation on depression, sexual dysfunction and quality of life.Methods: The premenopausal breast cancer patients who received ovarian function suppression were enrolled from seven hospital between June 2019 and June 2020. Our independent variable was the type of ovarian suppression, categorized as Ovarian Ablation (OA cohort, n=174) and medical GnRH agonist (GnRHa cohort, n=389). The self-administered questionnaire (OFS-Q5) was developed and used in this study aimed to assess the depression (PHQ-9), sexual dysfunction (FSFI) and quality of life (EORTC QLQ-BR23).Results: In this cross-sectional study, 563 patients with ovarian function suppression completed surveys were collected. The mean sum score of the PHQ-9 tend to be slight decrease in GnRHa cohort than that in ovarian ablation (OA) cohort (11.4 ±5.7 vs. 12.8 ±5.8, OR=1.910, P=0.079). Patients with major depression (PHQ-9≧15) was indicated significantly fewer in GnRHa cohort (31.1% vs 40.2%, P=0.025). The more surprising correlation is less patients with sexual dysfunction (61.5%, FSFI< 23) in OA cohort, a remarkable increase in GnRHa cohort (72.2%, P = 0.011). The ratio of sexual dysfunction remained lower for ovarian ablation women in long-term ovarian suppression (duration of ovarian suppression > 2 years: OA vs GnRHa, OR=1.555, P=0.037). No significantly difference for most subscales of QLQ-BR23 between two cohorts was evident.Conclusions: Our current investigation demonstrate here for the first time that medical GnRHa resulted in favour depression, worse sexual function than those with ovarian ablation, with similar quality of life. This new understanding should help to improve and alleviate adverse effect in patients with diverse ovarian function suppression.","PeriodicalId":20307,"journal":{"name":"Poster Session Abstracts","volume":"53 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78191197","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: The present study is aimed at summarizing the clinicopathological characteristics, prognosis, and management of breast adenosquamous carcinoma (ASC). Methods: A population-based study was performed using retrospectively extracted data from the Surveillance, Epidemiology and End Results database for breast cancer patients with histological diagnoses of ASC, infiltrating duct carcinoma (IDC) and squamous cell carcinoma (SCC) from 2004 to 2016. End-points were overall survival (OS) and breast cancer-specific mortality (BCSM). Propensity Score Matching (PSM) was employed to minimize selection bias of baseline characteristics. Univariable and multivariable analyses were used for identifying valuable prognostic factors. Results: ASC presented similar tumor size but low histological grade and less lymph node metastasis compared to IDC. ASC expressed less positive rate of hormone receptors and barely HER2, which was similar with SCC (estrogen receptor (ER): ASC 27.74% and SCC 21.53%, progesterone receptor (PR): ASC 18.06% and SCC 12.85%, HER2: ASC 4.44% and SCC 7.53%). ASC patients underwent the same treatment as IDC (chemotherapy 36.99% vs. 41.86%, BCS 50.58% vs 52.83%, P >0.05), only with less radiotherapy (39.88% vs. 48.34%, P<0.05). Median follow-up data of 78 months showed that the prognosis of IDC patients was better than that of ASC patients (all P <0.05 for BCSM and OS). After adjustment for clinicopathological and therapeutic factors in Cox proportional hazards models, ASC was no longer an independent poor prognosis factor. In matched groups, no significant difference in BCSM nor OS was observed between ASC and IDC groups. In HR-negative patients, the prognosis of ASC was similar with that of IDC, and both were superior to SCC. In HR-positive patients, the five-year survival rate of ASC was only about 60%, which was far less than that in ASC of HR-negative, the poor prognosis of ASC was closer to that of SCC. Multivariate analysis showed that older age (age≥60) and advanced AJCC stage (III and IV) were independent factors of poor prognosis in ASC, breast-conserving surgery was also ideally suited for ASC. Conclusions: ASC has unique clinicopathological characteristics and prognosis. To improve the clinical and biological understanding of ASC can make breast cancer patients get more individualized treatment.
{"title":"Abstract PS7-60: Adenosquamous carcinoma of the breast: A population-based study using the SEER database","authors":"Zhangyuan Gu, Juan Liu, Xiaoyan Lin, Cheng Wang, Jiejing Li, Yun Fu, Xiaolin Cheng, Cheng Xu, Zhigang Zhuang","doi":"10.21203/rs.3.rs-50772/v1","DOIUrl":"https://doi.org/10.21203/rs.3.rs-50772/v1","url":null,"abstract":"\u0000 Background: The present study is aimed at summarizing the clinicopathological characteristics, prognosis, and management of breast adenosquamous carcinoma (ASC). Methods: A population-based study was performed using retrospectively extracted data from the Surveillance, Epidemiology and End Results database for breast cancer patients with histological diagnoses of ASC, infiltrating duct carcinoma (IDC) and squamous cell carcinoma (SCC) from 2004 to 2016. End-points were overall survival (OS) and breast cancer-specific mortality (BCSM). Propensity Score Matching (PSM) was employed to minimize selection bias of baseline characteristics. Univariable and multivariable analyses were used for identifying valuable prognostic factors. Results: ASC presented similar tumor size but low histological grade and less lymph node metastasis compared to IDC. ASC expressed less positive rate of hormone receptors and barely HER2, which was similar with SCC (estrogen receptor (ER): ASC 27.74% and SCC 21.53%, progesterone receptor (PR): ASC 18.06% and SCC 12.85%, HER2: ASC 4.44% and SCC 7.53%). ASC patients underwent the same treatment as IDC (chemotherapy 36.99% vs. 41.86%, BCS 50.58% vs 52.83%, P >0.05), only with less radiotherapy (39.88% vs. 48.34%, P<0.05). Median follow-up data of 78 months showed that the prognosis of IDC patients was better than that of ASC patients (all P <0.05 for BCSM and OS). After adjustment for clinicopathological and therapeutic factors in Cox proportional hazards models, ASC was no longer an independent poor prognosis factor. In matched groups, no significant difference in BCSM nor OS was observed between ASC and IDC groups. In HR-negative patients, the prognosis of ASC was similar with that of IDC, and both were superior to SCC. In HR-positive patients, the five-year survival rate of ASC was only about 60%, which was far less than that in ASC of HR-negative, the poor prognosis of ASC was closer to that of SCC. Multivariate analysis showed that older age (age≥60) and advanced AJCC stage (III and IV) were independent factors of poor prognosis in ASC, breast-conserving surgery was also ideally suited for ASC. Conclusions: ASC has unique clinicopathological characteristics and prognosis. To improve the clinical and biological understanding of ASC can make breast cancer patients get more individualized treatment.","PeriodicalId":20307,"journal":{"name":"Poster Session Abstracts","volume":"27 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89902784","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2020-02-15DOI: 10.1158/1538-7445.sabcs19-p2-12-01
I. Nivar, Tara Kauffman, L. Bayne, P. Wiley, B. Goodspeed, Michael D. Feldman, L. Chodosh, A. Clark, A. DeMichele
Background: Patients (pts) treated for early stage breast cancer (BC) have a 30% lifetime risk of developing incurable, distant metastatic disease. Yet, standard monitoring after definitive therapy for primary disease is passive observation. Numerous studies have demonstrated that dormant bone marrow (BM) disseminated tumor cells (DTCs) are independently associated with recurrence, but assessment of DTCs is not performed in clinical practice, largely because of concerns about the acceptability and logistics of bone marrow aspiration (BMA) and lack of established therapies that target DTCs. As part of a large scale screening study for a clinical trial targeting DTCs, we examined pt attitudes about DTC screening and subsequently assessed feasibility and tolerability of BM DTC assessment. Methods: The PENN-SURMOUNT (Surveillance Markers of Utility for Recurrence after (Neo)adjuvant Therapy) Screening Study is a single center prospective, longitudinal cohort study examining BM and blood biomarkers of minimal residual disease (MRD) among pts within 5 years of BC diagnosis, who meet one of the following high risk criteria: positive axillary nodes, triple negative biology, ER+ with Oncotype Dx ≥ 25 and/or high risk Mammaprint, or residual disease (RD) after neoadjuvant chemotherapy (NACT). Consented pts undergo a baseline outpatient BMA; if negative, pts can repeat screening annually. During trial design, we surveyed 25 women with stage 2-3 BC at random from the breast clinic at the University of Pennsylvania to assess feasibility. On the SURMOUNT Study, we collected demographic and clinical characteristics of pts, and patient-centered survey data regarding feasibility and acceptability of the BMA that is administered within 48 hours of the procedure. Results: In the pre-trial feasibility survey, 21/25 (84%) pts indicated they were very/definitely interested in knowing if they harbored DTCs. Of those, 18 (86%) indicated moderate/definite interest in testing for DTCs with BMA after the BMA was described to them in detail. 20 (95%) of pts indicated moderate/definite interest in taking oral therapy to eradicate DTCs. 14 (67%) pts stated undergoing up to 3 additional BMA would not change their likelihood of undergoing the clinical trial; only 1 stated much less likely. In the subsequent SURMOUNT study, 361 pts have been referred to date; 167 were eligible, and 136 (81%) subsequently enrolled. 21 (13%) are still in screening. 130 pts have had at least 1 BMA with annual re-screens in 37 (year 1) and 8 (year 2). 39% traveled >50 miles to participate. Post-BMA symptoms were rare (bleeding 2%; redness 12%) though 59%/70% reported mild-moderate pain/tenderness. After BMA, 47%/29%/25% reported it was better/same/worse than expected. 30%/32%/22% reported minimal/moderate/high anxiety prior to the BMA. Afterward, only 20%/5%/4% reported minimal/moderate/high residual anxiety. In 128 pts with results, 38 (30%) have ≥ 1 DTC (30 initial, 8 on follow-up); by risk group:
背景:接受早期乳腺癌(BC)治疗的患者有30%的终生发展为无法治愈的远处转移性疾病的风险。然而，原发性疾病确诊治疗后的标准监测是被动观察。大量研究表明，休眠骨髓(BM)弥散性肿瘤细胞(dtc)与复发独立相关，但在临床实践中没有对dtc进行评估，主要是因为对骨髓穿刺(BMA)的可接受性和物流的担忧，以及缺乏针对dtc的既定治疗方法。作为针对DTC临床试验的大规模筛选研究的一部分，我们调查了患者对DTC筛查的态度，随后评估了BM DTC评估的可行性和耐受性。方法:PENN-SURMOUNT((新)辅助治疗后复发监测标志物)筛查研究是一项单中心前瞻性纵向队列研究，在BC诊断后5年内符合以下高风险标准之一的患者中检查BM和最小残留病(MRD)的血液生物标志物:腋窝淋巴结阳性，生物学三阴性，ER+， Oncotype Dx≥25和/或高危Mammaprint，或新辅助化疗(NACT)后残留疾病(RD)。同意的患者接受基线门诊BMA;如果阴性，PTS可以每年重复筛查一次。在试验设计期间，我们从宾夕法尼亚大学乳腺诊所随机调查了25名2-3期BC的妇女，以评估可行性。在SURMOUNT研究中，我们收集了患者的人口学和临床特征，以及以患者为中心的关于在手术后48小时内给予BMA的可行性和可接受性的调查数据。结果:在试验前的可行性调查中，21/25(84%)的患者表示他们非常/肯定有兴趣知道他们是否有dtc。其中，18人(86%)在详细描述BMA后表示有中度/明确的兴趣检测dtc伴BMA。20%(95%)的患者表示对口服治疗根除dtc有中度/明确的兴趣。14名(67%)患者表示接受最多3次额外BMA不会改变他们进行临床试验的可能性;只有1人认为可能性很小。在随后的SURMOUNT研究中，迄今已有361例患者;167例符合条件，136例(81%)随后入组。21例(13%)仍在筛查中。在37年(第1年)和8年(第2年)中，130名患者至少有1次BMA，每年重新筛查一次。39%的人旅行超过50英里参加。bma后症状罕见(出血2%;发红12%)，但59%/70%报告轻度至中度疼痛/压痛。在BMA之后，47%/29%/25%的受访者表示比预期更好/相同/更差。30%/32%/22%在BMA前报告有轻微/中度/高度焦虑。之后，只有20%/5%/4%的人报告了轻微/中度/高度的残余焦虑。在128名有结果的患者中，38名(30%)患者的DTC≥1(30名初始患者，8名随访患者);分危险组:淋巴结阳性20/77(26%)，三阴性20/64 (31%)，ER+/RS≥25的3/8(38%)，术后RD的7/29(24%)。DTC+患者与DTC-患者在中位年龄(50.4)、种族、旅行距离、绝经状态和BMI方面相似。94%的DTC+患者进入了CLEVER临床试验。结论:大多数BC幸存者希望了解DTC状态;其中大多数人愿意接受BMA并参加临床治疗试验，许多人愿意出差参加，并愿意接受年度BMA评估。SURMOUNT的研究表明，筛查dtc对于确定针对MRD进行治疗干预以减少复发的患者是可行和有效的。引文格式:Isoris Nivar, Tara Kauffman, Lauren Bayne, Paul Wiley, Brooke Goodspeed, Michael Feldman, Lewis Chodosh, Amy Clark, Angela DeMichele。最小残留病(MRD)筛查对治疗干预的患者态度、经验和结果[摘要]。摘自:2019年圣安东尼奥乳腺癌研讨会论文集;2019年12月10日至14日;费城(PA): AACR;中国癌症杂志，2020;31(增刊):02 - 02。
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