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Background: The Metastatic Breast Cancer Project (MBCproject) is an ongoing research study that directly engages patients (pts) through social media and advocacy groups, and empowers them to share their biospecimens, clinical history, and experiences. The goal is to create a publicly available dataset of linked clinicogenomic and pt-reported data to enable research. From 2015-10-20 to 2020-3-31, 3,245 MBC pts who received treatment at >1,700 institutions, consented to share medical records, pt-reported data, and tumor/saliva/blood samples and to have genomic analysis performed. Here, we describe an analysis of the clinical and genomic features in this initial MBCproject cohort. Methods: We performed whole exome sequencing (WES) on 379 tumors (with matched germline) from 301 pts, 377 germline samples and RNA sequencing (RNA-seq) from 200 tumors from 141 pts. In 14 pts, we characterized 2 or more serial tumor biopsies. WES data was analyzed for mutations and copy number variants. RNA-seq data was used to call fusions, research-grade PAM50, and gene set enrichment scores. Medical records and pt-reported data were abstracted to create detailed clinical record for each pt. Results: WES of 249 metastatic tumors identified 34 cancer genes (e.g., TP53, PIK3CA, CDH1, PTEN, AKT1, NF1, ESR1) that were significantly recurrently altered. Potential clinically actionable alterations were identified in 39% of metastatic tumors. 45 tumors (22.5%) had fusions with known functional effects and 24 (12%) had in-frame fusions in key cancer genes like FANCD2 (3), FGFR3 (2), ESR1 (1), BRAF (1), and NCOR1 (1). PAM50 classification suggested depletion of Luminal A subtype in this cohort compared to TCGA breast cancer cohort (p-value Citation Format: Esha Jain, Dewey Kim, Jorge Gomez Tejeda Zanudo, Sara Balch, Mary McGillicuddy, Brett N. Tomson, Tania G. Hernandez, Beena S. Thomas, Daniel L. Abravanel, Shahrayz Shah, Rafael Ramos, Delia Sosa, Ilan Small, Lauren Sterlin, Sarah Winnicki, Colleen Nguyen, Micheal Dunphy, Elana Anastasio, Todd R. Golub, Corrie A. Painter, Nikhil Wagle. The metastatic breast cancer project - Expanding the clinical, genomic, and transcriptomic landscape of metastatic breast cancer through patient-partnered research [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr PD6-02.