Abstract OT2-05-03: The metastatic breast cancer project: A national direct-to-patient research initiative to accelerate genomics research

Abstract

Abstract Over the past decade, genomic characterization of tumors has shed enormous light on the molecular underpinnings of cancer. These discoveries have led to the development of novel therapies and preventive measures that have already revolutionized cancer care. Despite this progress, the genomics of metastatic breast cancer (MBC), one of the leading causes of cancer death in the U.S., remains poorly understood. The challenge in studying tumor samples from patients with MBC has been that the tumors from most patients are not available for research, largely because the vast majority of patients are cared for in community settings where genomics studies are not typically conducted. To address this, we have launched a nationwide study, The Metastatic Breast Cancer Project, which seeks to empower patients to accelerate cancer research through sharing their samples and clinical information. We have developed an outreach program in collaboration with MBC advocacy organizations to connect MBC patients around the country with genomics research performed at the Broad Institute, allowing them to participate regardless of where they live. Working with MBC patients and advocates, we designed a website (www.mbcproject.org) with an online questionnaire that allows patients with MBC to provide information about themselves and their cancer. Based on their answers, patients are offered an electronic consent form that explains the risks and benefits of the study and asks for permission to obtain a portion of their stored tumor tissue, a saliva sample, and copies of their medical records. For patients who consent, our clinical research team contacts their physicians and obtains copies of their medical records, which are reviewed to confirm eligibility. Enrolled patients are sent a saliva kit and asked to mail back a saliva sample, which is used to extract germline DNA. The clinical research team also contacts the patient's pathology department and requests a portion of the tumor to be sent to the Broad Institute for genomic analysis. Whole exome and transcriptome sequencing is performed on tumor and germline DNA. Sequencing data are linked to de-identified clinical information, and the resulting data are used to identify drivers of tumorigenesis, mechanisms of response and resistance to therapies, and diagnostic, prognostic, and therapeutic biomarkers. The database of clinically annotated genomic information will be shared with the NIH and the cancer research community. Study updates and discoveries are shared at regular intervals with all patients who complete the initial questionnaire. This direct-to-patient approach should be particularly enabling for the identification of patients with rare phenotypes or clinical behavior. For this reason, the first cohorts being studied are patients with extraordinary responses to therapies and patients who present with de novo MBC. Additional cohorts will be added in the future, including young women with MBC and patients with drug-resistant MBC. This project seeks to establish a patient-researcher partnership to accelerate genomic discoveries and improve outcomes in MBC, and may ultimately serve as a means to build a new clinical and translational research model for all patients with cancer. Citation Format: Wagle N, Painter CA, Ilzarbe M, Van Allen EM, Frank E, Oh C, Krevalin M, Lloyd M, Anderka K, Kryukov G, Boehm JS, Winer E, Lander ES, Golub TR. The metastatic breast cancer project: A national direct-to-patient research initiative to accelerate genomics research. [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 OT2-05-03.