Abstract PD6-08: IMAGE: Individualized molecular analyses guide efforts in breast cancer with comprehensive genomic profiling of tissue and plasma tumor DNA
Authors: Parsons HA , Beaver JA , Cimino-Mathews A , Zorzi J , Slater S , Clark T , Lipson D , Ali SM , Kennedy M , Otto GA , Young LE , Jeter S , VanDenBerg DA , Rosner GL , Park BH , Stearns V 
Published: May 2016

Abstract
Background: Standard treatment options for patients with metastatic triple negative breast cancer (TNBC) are limited to chemotherapy. Molecular profiling of tumors may allow for novel treatment recommendations.
Methods: We initiated a prospective study designated IMAGE. Women with newly progressing metastatic TNBC who received at least one line of prior chemotherapy were eligible. New metastatic biopsies were obtained for molecular profiling at study entry. Archived metastatic biopsy specimens were allowed if patients had not commenced new systemic therapy. The specimens were reviewed by the study pathologist and stained for ER, PR, HER2, and androgen receptor (AR) by immunohistochemistry. Specimens underwent hybrid-capture based comprehensive genomic profiling (CGP) (Foundation Medicine Inc., Cambridge, MA). Clinical data and genomic profiling reports were reviewed by the GAITWAY (Genomic Alterations in Tumors with Actionable Yields) Molecular Profile Tumor Board. Recommendations were communicated to the treating oncologist and patients were followed for treatment decision and clinical outcomes. Peripheral blood was also analyzed by an investigational assay for circulating plasma tumor DNA (ptDNA) (Foundation Medicine Inc.) at study entry, and when obtainable, from serial blood draws at time of progression. The primary objective was to assess feasibility of completing the process from consent to GAITWAY recommendations within 28 days for at least 80% of patients.
Results: From September 2013 to April 2015, we enrolled 26 eligible women. Median age was 55 (range 25-67); patients identified as white 12 (46%), black 11 (42%), or other 3 (12%); median number of prior lines of treatment was 3; and 65.4% of patients had visceral disease. Twenty (77%) eligible patients received CGP of a metastatic site biopsy. Six patients did not undergo CGP due to either absence of a metastatic site amenable for biopsy or inadequate tissue for CGP. The study met the predefined statistical endpoint for futility and was closed after 20 patients had undergone CGP. Twelve (60%) evaluable patients received treatment recommendations within 28 days of study consent. Failure to meet this time frame was due to difficulties in accessing archival tumor tissue (N=5) and need for additional tissue for molecular analysis (N=3). Preliminary results demonstrate high concordance between mutations in metastatic biopsies and ptDNA in 15/17 patients.
Enrolled in IMAGE26Successful NGS20Potentially actionable mutation identified15GAITWAY recommended targeted therapy as possible next treatment13Received targeted therapy4
Conclusions: CGP of patients with metastatic TNBC can provide additional information that may help direct treatment. However, difficulties in obtaining adequate tumor tissue may hinder this approach. Use of a well-validated ptDNA profiling assay could be an alternative to overcome these limitations.
Citation Format: Parsons HA, Beaver JA, Cimino-Mathews A, Zorzi J, Slater S, Clark T, Lipson D, Ali SM, Kennedy M, Otto GA, Young LE, Jeter S, VanDenBerg DA, Rosner GL, Park BH, Stearns V. IMAGE: Individualized molecular analyses guide efforts in breast cancer with comprehensive genomic profiling of tissue and plasma tumor DNA. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr PD6-08.