Abstract OT1-2-01: Circulating tumor DNA in plasma as a surrogate for tumor biopsy to identify tumor genetic alterations in patients with multi-focal metastatic breast cancer
Authors: Chamberlin Mary D , Miller Todd W , Bean Jennifer R , Barth Richard J , Rosenkranz Kari M , Marotti Jonathan D , Gemery John M , Gui Jiang 
Published: May 2015

Abstract
Background: While effective targeted therapies exist for patients with ER/PR + (anti-estrogens) and HER2+ (anti-HER2 agents) disease, and some triple-negative cancers respond to DNA-damaging chemotherapy, many patients eventually exhibit disease refractory to all standard breast cancer therapies, particularly in the metastatic setting. Expanding catalogs of tumor-targeted therapies are being developed, and tumor genetics are playing an increasing role in patient selection. However, tumors can exhibit intra- and inter-tumor genetic heterogeneity. If a biopsied tumor is not genetically reflective of all tumors within a patient, then the optimal therapy may be overlooked. Identifying targetable genetic changes for which there are drugs, using non-invasive procedures, will be an increasing challenge for medical oncologists. One way to potentially overcome this issue is through cell-free circulating tumor DNA, which is detectable in the bloodstream. This study represents the first step in this important process: evaluating plasma DNA as a potential route to non-invasive identification of genetic mutations in patients with metastatic breast cancer with several tumors.
Design: Patients with new or progressive metastatic breast cancer with &gt;=3 sites of biopsy-able disease are enrolled. Large bore, large volume blood draw for PT/ INR and plasma DNA will be obtained. Primary tumor will be biopsied if present. Biopsies of &gt;=3 tumors in &gt;=2 different organ sites will be required. Tumor histology and ER/PR/her2 status will be determined. Tumor tissue and plasma will undergo DNA sequencing.
Eligibility: Measureable new or progressive metastatic breast cancer by CT and bone scan or PET scan.
&gt;=3 sites of disease with &gt;=2 organ sites appropriate for biopsy. Prior therapy allowed, but all specimens must be obtained prior to change in therapy.
Primary objective: To determine whether the genetic mutations in plasma DNA are reflective of the genetic mutations present in biopsies of all tumors.
Secondary objectives: To determine A) the amount of plasma DNA required to capture all somatic genetic mutations in tumor samples, and B) the extent of genetic heterogeneity between primary and metastatic tumors.
Primary endpoint: Rate of genetic concordance between plasma DNA and &gt;=3 tumor within each patient.
Present accrual: 2 Target accrual: 10.
Citation Format: Mary D Chamberlin, Todd W Miller, Jennifer R Bean, Richard J Barth, Kari M Rosenkranz, Jonathan D Marotti, John M Gemery, Jiang Gui. Circulating tumor DNA in plasma as a surrogate for tumor biopsy to identify tumor genetic alterations in patients with multi-focal metastatic breast cancer [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr OT1-2-01.