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Circulating plasma tumor DNA as a biomarker for early stage breast cancer

循环血浆肿瘤 DNA 作为早期乳腺癌的生物标志物

基本信息

批准号：
9392301
负责人：
BEN H PARK
金额：
$ 6.8万
依托单位：
JOHNS HOPKINS UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-09-26 至 2021-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9392301
关键词：
Address Biological Markers Biopsy Blood Blood Circulation Blood Tests Blood specimen Breast Breast Cancer Patient Breast Cancer therapy Breast Oncology Cancer Patient Clinical Clinical Oncology Clinical Trials DNA DNA Markers Data Detection Diagnostic Disease Ensure Evaluable Disease Evolution Family Foundations Future Goals Human In complete remission Individual Knowledge Lead Liquid substance Local Therapy Malignant Neoplasms Malignant neoplasm of anus Measures Methods Microscopic Mind Modeling Mutation Neoadjuvant Therapy Oncogenes Oncologist Operative Surgical Procedures Pathologic Patient risk Patients Physicians Plasma Polymerase Chain Reaction Postoperative Period Predictive Value Primary Neoplasm Prior Therapy Public Health Publishing Radiation therapy Recurrence Research Residual Cancers Residual Tumors Residual state Risk Sample Size Sampling Somatic Mutation Specificity Systemic Therapy Technology Testing Therapeutic Time Toxic effect Tumor Burden Uncertainty Woman Work actionable mutation base burden of illness cancer cell chemotherapy clinical decision-making digital experience gene panel high risk improved outcome individual patient individualized medicine lymph nodes malignant breast neoplasm new technology new therapeutic target next generation sequencing outcome forecast patient population patient subsets peace personalized medicine precision medicine prospective public health relevance response trial design tumor tumor DNA virtual

项目摘要

DESCRIPTION (provided by applicant): Personalized medicine for breast oncology is in evolution. Currently, oncologists use prior clinical trials data to recommend multiple therapies based upon features of the tumor and clinical stage of the patient. A limitation with this approach is that these data are averaged from large groups of patients that are then applied to each individual. This creates uncertainty as there is currently no reliable method to identify individua patients who truly have microscopic residual disease after primary therapy from those that are already cured. Thus, oncologists tend to treat the majority of patients with multiple therapies knowing from past clinical trials that most patients do not need these additional therapies, resulting in overtreatment. This project proposes an alternative model that will lead to a paradigm shift in how oncologists recommend and follow responses to therapy. The research team proposes that using the newer technologies of droplet digital PCR (ddPCR) and next generation sequencing (NGS), plasma tumor DNA (ptDNA) molecules shed into the circulation from cancer cells can be reliably detected and measured. They have already demonstrated the ability to detect microscopic residual disease using these technologies in early stage breast cancer patients. The team proposes a transforming project to address specific unmet needs in early stage (curative intent) breast cancer. It is well known that there are subsets of breast cancer patients who upon completion of preoperative chemotherapy (neoadjuvant therapy; NAT) have no evidence of cancer in the breast and lymph nodes. This is termed a pathologic complete response (pCR), and is associated with a favorable prognosis. This raises the question of whether these patients need surgery after NAT, however, patients must undergo surgery to know that they have achieved a pCR. The team will solve this conundrum by determining if the absence of detectable ptDNA after NAT will predict for a pCR and they will therefore define a "liquid pCR". Based on their data, the team hypothesizes that >95% of patients without detectable ptDNA after NAT will have a pCR. This will set the stage for future studies to determine if patients without detectable ptDNA after NAT can safely forego surgery and/or radiation therapy, similar to the paradigm shift in treating anal cancer decades ago. A second long-term goal of this work is to determine in future studies whether the presence of ptDNA after NAT identifies a subset of patients with significant risk for future recurrence, which could therefore serve as a platform for clinical trials with new targeted therapies for patients wih detectable ptDNA. Ultimately measuring ptDNA will enable individual therapy options and change the current practice of overtreatment in early stage disease.