权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Molecular complete response in blood as a predictor for pathologic complete response after neoadjuvant therapy for breast cancer

血液中的分子完全缓解作为乳腺癌新辅助治疗后病理完全缓解的预测因子

基本信息

批准号：
9520587
负责人：
BEN H PARK
金额：
$ 22.47万
依托单位：
JOHNS HOPKINS UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-04-12 至 2018-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9520587
关键词：
Address Axillary Lymph Node Dissection Biological Markers Blood Blood Circulation Blood Tests Blood specimen Breast Cancer Patient Breast Cancer gene Breast Cancer therapy Cancer Patient Clinical Clinical Oncology Clinical Trials DNA Data Detection Detection of Minimal Residual Disease Diagnostic Disease ERBB2 gene Evaluable Disease Family Foundations Future In complete remission Individual Knowledge Lead Liquid substance Local Therapy Logistics Malignant Neoplasms Measures Methods Microscopic Mind Molecular Monitor Mutation Mutation Detection Neoadjuvant Therapy Oncologist Operative Surgical Procedures Pathologic Patient risk Patients Physicians Plasma Polymerase Chain Reaction Postoperative Period Predictive Value Prior Therapy Public Health Publishing Radiation therapy Recurrence Regimen Research Residual Cancers Residual Tumors Residual state Risk Sampling Sensitivity and Specificity Sentinel Lymph Node Biopsy Somatic Mutation Source Specificity Systemic Therapy Technology Testing Therapeutic Time Tissue Sample Tissues Toxic effect Tumor Burden Tumor Tissue Woman Work base burden of illness cancer cell chemotherapy digital exhaust experience gene panel high risk individual patient individualized medicine malignant breast neoplasm neoplastic cell new technology next generation sequencing outcome forecast overtreatment patient population patient subsets peace precision medicine prospective response success treatment planning trial design tumor tumor DNA virtual

项目摘要

Project Summary/Abstract The ability to treat breast cancer using patient specific regimens is not yet feasible. For example, oncologists use prior clinical trials data to recommend multiple therapies based upon features of the tumor and clinical stage of the patient. However, these data are averaged from large groups of patients that are then applied to each individual. Therefore, oncologists end up treating the majority of patients with multiple therapies knowing from past clinical trials that most patients do not need these additional therapies, resulting in overtreatment. For early stage breast cancer, this is because there is no reliable method to identify patients that truly have microscopic residual disease after primary therapy versus those that are already cured. The proposed project addresses this conundrum. The research team will employ the newer technologies of digital PCR (dPCR) and next generation sequencing (NGS), to reliably detect and quantify plasma tumor DNA (ptDNA) molecules shed into the circulation from cancer cells. They have already demonstrated the ability to detect microscopic residual disease using these technologies in early stage breast cancer patients. The team proposes an ambitious project to address unmet needs in early stage (curative intent) breast cancer, to ultimately determine who truly needs additional therapy vs. those patients that are already cured. They propose to evaluate Stage II/III breast cancer patients undergoing neoadjuvant therapy (NAT) and define whether absence of ptDNA after NAT can predict for complete elimination of tumor cells at the time of surgery, termed a pathologic complete response (pCR). Three specific aims are proposed. Aim 1) Identification of somatic mutations in early stage breast cancer using NGS. The team will test the feasibility of using plasma DNA to identifying tumor specific mutations in Stage II/III breast cancer patients prior to any therapy. The success of this aim will preclude the need for obtaining diagnostic tissue samples for NGS, which are often exhausted or unobtainable. Aim 2) Detection of somatic mutations in plasma using dPCR. The successful detection of mutations in preNAT blood by dPCR will validate mutation markers for serial testing of blood samples for each individual patient. Aim 3) Predictive value of ptDNA for residual disease and pathologic complete response (pCR). Using dPCR, the team will determine whether absence of ptDNA in blood after NAT but prior to surgery predicts for pCR. The success of this study will set the stage for future trials to determine if patients without detectable ptDNA after NAT can safely forego surgery, similar to the paradigm shift in using sentinel lymph node biopsies to avoid axillary dissection. Additionally, the presence of ptDNA after NAT and surgery may identify a subset of patients with significant risk for future recurrence, which could serve as a platform for future clinical trials. Ultimately measuring ptDNA will enable individual therapy options and change the current practice of overtreatment in early stage disease.

项目总结/文摘