Abstract OT2-06-03: METAMORPH: METAstatic markers of recurrent tumor PHenotype for breast cancer

Up to 30% of patients diagnosed with breast cancer will develop recurrent disease within their lifetime, and currently this form of the disease is incurable. There are unmet needs to better understand underlying metastatic biology, identify new therapeutic targets and develop better methods for monitoring changes in disease, both to monitor response and elucidate resistance mechanisms. To address these needs, the METAMORPH Study encompasses a comprehensive approach that combines serial molecular tissue profiling at the RNA and DNA level with circulating markers (DTCs, CTCs, plasma tumor DNA), and ongoing assessment of therapeutic response. METAMORPH is a prospective cohort study of women with suspected or confirmed recurrent breast cancer and accessible tumor by standard clinical biopsy, who are enrolled at the University of Pennsylvania prior to starting a new therapy for recurrent metastatic disease. The aims of this trial are to (1) evaluate the mechanisms through which recurrent breast cancer are genetically distinct from the primary tumor, (2) evaluate the circulating tumor biomarker trajectory of recurrent disease, (3) elucidate “escape pathways” of progressing tumors that emerge during the selective pressure of therapy, and (4) explore clinical utility of tumor and blood testing. The study protocol integrates research aims into clinical care, including a standardized approach to disease assessment and biopsy, pathologic confirmation of histology and receptor subtype, panel-based CLIA-approved genomic profiling, collection of research specimens, and standardized reporting of results, which are returned to patients and physicians. Patients are followed for treatment and outcome, and serial samples are collected at progression. A companion protocol, COMET, provides education about genomic testing and assesses patient understanding and impact of results. To date, 155 patients have enrolled, 142 (92%) have been biopsied, 120 (77%) have had sufficient DNA for molecular profiling and 109 (70%) have had genomic panel testing. Accrual is ongoing, with an initial target of 300 patients. Multiple sites within the UPHS Health System are enrolling. Contact information: angela.demichele@uphs.upenn.edu. Key words: Metastatic disease, tumor profiling. Citation Format: DeMichele A, Soucier-Ernst DJ, Clark C, Shih N, Stavropoulos W, Maxwell KN, Feldman M, Lierbamen D, Morrissette JJD, Paul MR, Pan T-C, Wang J, Belka GK, Chen Y, Yee S, Carpenter E, Fox K, Matro J, Clark A, Shah P, Domchek S, Bradbury A, Chodosh L. METAMORPH: METAstatic markers of recurrent tumor PHenotype for breast cancer [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr OT2-06-03.