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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 samples, clinical information, and experiences. The goal is to create a publicly available dataset of linked genomic, clinical, and pt-reported data to enable research. In collaboration with pts, advocates, and advocacy groups, a website (MBCproject.org) was developed that allows pts with metastatic breast cancer (MBC) anywhere in the US or Canada to register. From 10/20/15-6/1/21, 6100 patients with MBC registered for the MBCproject. Registered pts are sent an online consent form that asks for permission to obtain and analyze their medical records and samples. Consented pts are sent a saliva and/or blood kit and asked to mail back a saliva sample, which is used to extract germline DNA, and/or a blood sample, which is used to extract germline DNA and cell free DNA (cfDNA). We contact participants’ medical providers to obtain medical records and a portion of their stored tumor biopsies. 3456 pts receiving care at over 1700 different institutions have consented to share medical records and tumor/saliva/blood samples and to have genomic analysis performed. Whole exome sequencing (WES) is performed on tumor DNA, germline DNA, and cfDNA; transcriptome sequencing (RNA-seq) is performed on tumor RNA. Medical records and pt-reported data are abstracted to create a detailed clinical record for each pt. Table 1 highlights clinical data collection, biospecimen acquisition, and genomic data generation to date. Examples of clinicogenomic analyses are shown in Table 2. De-identified linked genomic, clinical, and pt-reported data is shared regularly via public databases (mbcproject.org, cBioPortal, dbGaP, NCI Genomic Data Commons). To date, this data has been cited in over 40 publications. Study updates are shared with participants regularly. The MBCproject continues to enroll new patients, generate additional data, and perform integrated clinical and genomic analyses with the goal of building a dataset that is representative of patients with MBC. We have partnered with over 30 non-profit breast cancer advocacy groups. We also have several community engagement efforts underway to more directly reach patients in underrepresented communities, including partnerships with faith-based organizations and colleges/universities, as well as targeted engagement with the African American community. In addition, in partnership with Latinx patients, advocates, and researchers, a Spanish-language version of the MBCproject was launched in June 2021. Partnering directly with pts rapidly enables thousands of pts to remotely share tumors, blood, saliva, and medical records to accelerate research. The resulting publicly shared clinically annotated dataset is a resource that allows researchers to identify patients with specific phenotypes, who have often been challenging to identify with traditional approaches. Clinical data collection, biospecimen acquisition, and genomic data generation:NumberConsent signed (US & CA)3456 ptsPatient-reported data collected (demographics, diagnosis details, receptor status, clinical experiences, pathology details, sites of metastasis, treatments with start and stop dates3456 ptsMedical record received from clinical institution1365 ptsSaliva sample received from pt2124 ptsBlood sample received from pt1114 ptsTumor samples received from clinical institution631 tumor samples from 398 ptsWES from germline complete505 germline samplesWES from tumor (primary and metastatic) samples complete429 tumor samplesRNA-seq from tumor (primary and metastatic) samples complete351 tumor samplesULP-WGS from cfDNA (taken in metastatic setting) complete953 blood samplesWES from circulating tumor DNA (taken in metastatic setting) complete144 blood samples CohortConsented (US & CA)Tumor WES completeTumor RNA-seq completePts diagnosed < 40 yrs of age114615292De novo MBC1207158109Late recurrence (>5 years after dx)9099141Long term survivors (MBC > 10yrs)163138Resistance to CDK4/6 inhibitors70914839NED at time of f/u survey4305445Triple Negative Breast Cancer3304632Patients with 2 or more tumor biopsies/cfDNA samples collected by the MBCproject29810882 Citation Format: Nikhil Wagle, Corrie Painter, Elana Anastasio, Mary McGillicuddy, Esha Jain, Tania G. Hernandez, Brett N. Tomson, Beena Thomas, Daniel Abravanel, Dewey Kim, Sara Balch, Alyssa L. Damon, Shahrayz Shah, Rafael Ramos, Delia Sosa, Ilan Small, Colleen Nguyen, Sarah Winnicki, Taylor Cusher, Parker Chastain, Michael Dunphy, Jorge Gomez Tejeda Zanudo, Netsanet Tsegai, Lauren Sterlin, Ulcha F. Ulysse, Imani Boykin, Oyin Alao, Todd R. Golub. The metastatic breast cancer project: Generating the clinical and genomic 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 OT1-19-01.

Molecular profiling studies have enabled discoveries for metastatic prostate cancer (MPC) but have predominantly occurred in academic medical institutions and involved non-representative patient populations. We established the Metastatic Prostate Cancer Project (MPCproject, mpcproject.org), a patient-partnered initiative to involve patients with MPC living anywhere in the US and Canada in molecular research. Here, we present results from our partnership with the first 706 MPCproject participants. While 41% of patient partners live in rural, physician-shortage, or medically underserved areas, the MPCproject has not yet achieved racial diversity, a disparity that demands new initiatives detailed herein. Among molecular data from 333 patient partners (572 samples), exome sequencing of 63 tumor and 19 cell-free DNA (cfDNA) samples recapitulated known findings in MPC, while inexpensive ultra-low-coverage sequencing of 318 cfDNA samples revealed clinically relevant

Despite rare cancers accounting for 25% of adult tumors1, they are difficult to study due to the low disease incidence and geographically dispersed patient populations, which has resulted in significant unmet clinical needs for patients with rare cancers. We assessed whether a patient-partnered research approach using online engagement can overcome these challenges, focusing on angiosarcoma, a sarcoma with an annual incidence of 300 cases in the United States. Here we describe the development of the Angiosarcoma Project (ASCproject), an initiative enabling US and Canadian patients to remotely share their clinical information and biospecimens for research. The project generates and publicly releases clinically annotated genomic data on tumor and germline specimens on an ongoing basis. Over 18 months, 338 patients registered for the ASCproject, which comprises a large proportion of all patients with angiosarcoma. Whole-exome sequencing (WES) of 47 tumors revealed recurrently mutated genes that included KDR, TP53, and PIK3CA. PIK3CA-activating mutations were observed predominantly in primary breast angiosarcoma, which suggested a therapeutic rationale. Angiosarcoma of the head, neck, face and scalp (HNFS) was associated with a high tumor mutation burden (TMB) and a dominant ultraviolet damage mutational signature, which suggested that for the subset of patients with angiosarcoma of HNFS, ultraviolet damage may be a causative factor and that immune checkpoint inhibition may be beneficial. Medical record review revealed that two patients with HNFS angiosarcoma had received off-label therapeutic use of antibody to the programmed death-1 protein (anti-PD-1) and had experienced exceptional responses, which highlights immune checkpoint inhibition as a therapeutic avenue for HNFS angiosarcoma. This patient-partnered approach has catalyzed an opportunity to discover the etiology and potential therapies for patients with angiosarcoma. Collectively, this proof-of-concept study demonstrates that empowering patients to directly participate in research can overcome barriers in rare diseases and can enable discoveries. A framework of patient-partnered research allows patients with angiosarcoma to share their samples and clinical records securely to accelerate molecular characterization of tumors and identification of therapeutic approaches.

Molecular profiling studies have enabled numerous discoveries for metastatic prostate cancer (MPC), but they have mostly occurred in academic medical institutions focused on select patient populations. We developed the Metastatic Prostate Cancer Project (MPCproject, mpcproject.org), a patient-partnered initiative to empower MPC patients living anywhere in the U.S. and Canada to participate in molecular research and contribute directly to translational discovery. Here we present clinicogenomic results from our partnership with the first 706 MPCproject participants. We found that a patient-centered and remote research strategy enhanced engagement with patients in rural and medically underserved areas. Furthermore, patient-reported data achieved 90% consistency with abstracted health records for therapies and provided a mechanism for patient-partners to share information about their cancer experience not documented in medical records. Among the molecular profiling data from 333 patient-partners (n = 573 samples), whole exome sequencing of 63 tumor samples obtained from hospitals across the U.S. and Canada and 19 plasma cell-free DNA (cfDNA) samples from blood donated remotely recapitulated known findings in MPC and enabled longitudinal study of prostate cancer evolution. Inexpensive ultra-low coverage whole genome sequencing of 318 cfDNA samples from donated blood revealed clinically relevant genomic changes like AR amplification, even in the context of low tumor burden. Collectively, this study illustrates the power of a longitudinal partnership with patients to generate a more representative clinical and molecular understanding of MPC.NoteTo assist our patient-partners and the wider MPC community interpret the results of this study, we have included a glossary of terms in the Supplementary Materials.

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.

Despite rare cancers accounting for 25% of adult tumors

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 samples, clinical information, and experiences. The goal is to create a publicly available dataset of linked genomic, clinical, and pt-reported data to enable research. In collaboration with pts, advocates, and advocacy groups, a website (MBCproject.org) was developed that allows pts with metastatic breast cancer (MBC) anywhere in the US or Canada to register. From 10/20/15-3/31/20, 5708 women and men with MBC registered for the MBCproject. Registered pts are sent an online consent form that asks for permission to obtain and analyze their medical records and samples. Consented pts are sent a saliva and/or blood kit and asked to mail back a saliva sample, which is used to extract germline DNA, and/or a blood sample, which is used to extract germline DNA and cell free DNA (cfDNA). We contact participants’ medical providers to obtain medical records and a portion of their stored tumor biopsies. 3245 pts receiving care at over 1700 different institutions have consented to share medical records and tumor/saliva/blood samples and to have genomic analysis performed. Whole exome sequencing (WES) is performed on tumor DNA, germline DNA, and cfDNA; transcriptome sequencing (RNA-seq) is performed on tumor RNA. Medical records and pt-reported data are abstracted to create a detailed clinical record for each pt. Table 1 highlights clinical data collection, biospecimen acquisition, and genomic data generation to date. Examples of clinicogenomic analyses are shown in Table 2. De-identified linked genomic, clinical, and pt-reported data is shared regularly via public and semi-public databases (mbcproject.org, cBioPortal, dbGaP, NCI Genomic Data Commons). To date, this data has been cited in over 20 published journal articles. Study updates are shared with participants regularly. The MBCproject continues to enroll new patients, generate additional data, and perform integrated clinical and genomic analyses with the goal of building a dataset that is representative of patients with MBC. We have partnered with over 30 non-profit breast cancer advocacy groups. We also have several community engagement efforts underway to more directly reach patients in underrepresented communities, including partnerships with faith-based organizations and colleges/universities, as well as targeted engagement with the African American community. In addition, in partnership with Latinx patients, advocates, and researchers, the project has been translated into Spanish and is expected to launch in late 2020. Partnering directly with pts rapidly enables thousands of pts to remotely share tumors, blood, saliva, and medical records to accelerate research. The resulting publicly shared clinically annotated database is a resource that allows researchers to identify patients with specific phenotypes, who have often been challenging to identify with traditional approaches. Clinical data collection, biospecimen acquisition, and genomic data generation:NumberConsent signed (US & CA)3245 ptsSurvey #1 submitted(demographics, diagnosis details, receptor status, clinical experiences)3245 ptsSurvey #2 submitted(pathology details, sites of metastasis, treatments with start and stop dates)1638 ptsMedical record received1352 ptsSaliva sample received2004 ptsBlood sample received1121 ptsTumor samples received585 tumor samples from 424 ptsDigital image of tumor slide H&E generated585 tumor samplesWES from germline complete458 germline samplesWES from tumor (primary and metastatic) samples complete343 tumor samplesRNA-seq from tumor (primary and metastatic) samples complete228 tumor samplesULP-WGS from cfDNA (taken in metastatic setting) complete993 blood samplesWES from circulating tumor DNA (taken in metastatic setting) complete143 blood samples CohortConsented (US & CA)Tumor WES completeTumor RNA-seq completePts diagnosed < 40 yrs of age107312071De novo MBC112712183Late recurrence (>5 years after dx)8307752Long term survivors (MBC > 10yrs)158115Resistance to CDK4/6 inhibitors70914839NED at time of f/u survey4238939Triple Negative Breast Cancer3107531Patients with 2 or more tumor biopsies / cfDNA samples collected by the MBCproject2876138 Citation Format: Nikhil Wagle, Corrie Painter, Elana Anastasio, Michael Dunphy, Mary McGillicuddy, Esha Jain, Brett Tomson, Tania G. Hernandez, Beena Thomas, Dewey Kim, Alyssa L. Damon, Shahrayz Shah, Rafael Ramos, Colleen Nguyen, Lee O'Neil, Sarah Winnicki, Sara Balch, Rachel Stoddard, Taylor Cusher, Parker Chastain, Jorge Gomez Tejeda Zanudo, Jorge Buendia-Buendia, Ofir Cohen, Netsanet Tsegai, Lauren Sterlin, Ulcha F. Ulysse, Imani Boykin, Kate Sine, Oyin Alao, Jacqueline Lucia, Eric S. Lander, Todd R. Golub. The metastatic breast cancer project: Generating the clinical and genomic landscape of metastatic breast cancer through patient-partnered research [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr OT-18-01.

Background: The Metastatic Breast Cancer Project (MBCproject) is a research study that directly engages patients (pts) through social media and advocacy groups, and empowers them to share their samples, clinical information, and experiences. The goal is to create a publicly available dataset of linked genomic, clinical, and pt-reported data to enable research. Methods: In collaboration with pts, advocates, and advocacy groups, a website (MBCproject.org) was developed that allows pts with metastatic breast cancer (MBC) anywhere in the U.S. or Canada to register. Registered pts are sent an online consent form that asks for permission to obtain and analyze their medical records and samples. Once enrolled, pts are sent a saliva kit and a blood kit and asked to mail back a saliva sample, which is used to extract germline DNA, and/or a blood sample, which is used to extract germline DNA and cell free DNA (cfDNA). We contact participants’ medical providers and obtain medical records and a portion of their stored tumor biopsies. Whole exome sequencing (WES) is performed on tumor DNA, germline DNA, and cfDNA; transcriptome sequencing (RNA-seq) is performed on tumor RNA. Medical records and pt-reported data are abstracted to create a detailed clinical record for each pt. All de-identified data are shared regularly via public databases (cbioportal.org, mbcproject.org, dbGaP, NCI Genomic Data Commons) without restrictions. Study updates are shared with participants regularly. Results: From 10/20/15-7/8/19, 5357 women and men with MBC registered. 3290 pts receiving care at over 1700 different institutions consented to share medical records and tumor/saliva/blood samples, and to have genomic analysis performed. Details of clinical data collection, biospecimen acquisition, and genomic data generation to date are outlined in the Table. WES from 463 tumors obtained from 326 pts have been generated (with matched germline WES), including 61 pts with 2 timepoints, 19 pts w 3 timepoints, and 11 pts w 4+ timepoints. 278 tumor exomes were from the breast/regional lymph nodes, 63 from distant metastatic sites and 122 from cfDNA. 110 tumor exomes were from samples obtained before the diagnosis of MBC, 258 from after the diagnosis of MBC, and 95 to be determined (TBD). 161 tumor exomes were obtained prior to any therapy, 204 following some therapy, and 98 TBD. Clinically annotated genomic data are used to study specific pt cohorts (including rare subsets and outliers) and to identify mechanisms of response and resistance to therapies. Examples of the clinical and genomic analyses that will be presented include: - Pts diagnosed 5 yrs after diagnosis (830 pts enrolled; 77 with tumor WES) - Long-term survivors, >10 yrs with MBC (159 pts enrolled; 11 with tumor WES) - Resistance to CDK4/6 inhibitors (709 pts enrolled; 148 with tumor WES) Conclusions: Partnering directly with pts enables rapid identification of thousands of pts willing to share tumors, blood, saliva, and medical records to accelerate research. This approach allows for identification of patients with specific phenotypes, who have been challenging to identify with traditional approaches. Remote acquisition of medical records and saliva/blood/tumor samples is feasible. This clinically annotated dataset is a shared resource for the research community. Table 1Clinical data collection, biospecimen acquisition, and genomic data generation:NumberConsent signed3290 ptsSurvey #1 submitted3290 pts(demographics, diagnosis details, receptor status, clinical experiences)Survey #2 submitted1435 pts(pathology details, sites of metastasis, treatments with start and stop dates)Medical record received1307 ptsSaliva sample received1976 ptsBlood sample received1121 ptsTumor samples received482 tumor samples from 346 ptsDigital image of tumor slide H&E generated482 tumor samplesWES from germline complete310 germline samplesWES from tumor sample complete341 tumor samplesRNA-seq from tumor sample complete229 tumor samplesULP-WGS from cfDNA complete947 blood samplesWES from circulating tumor DNA complete122 blood samples Citation Format: Nikhil Wagle, Corrie Painter, Elana Anastasio, Michael Dunphy, Mary McGillicuddy, Esha Jain, Tania G Hernandez, Sara Balch, Beena Thomas, Dewey Kim, Alyssa L. Damon, Shahrayz Shah, Brett N. Tomson, Rachel Stoddard, Colleen Nguyen, Jorge Buendia-Buendia, Ofir Cohen, Jorge Gomez Tejeda Zanudo, Netsanet Tsegai, Lauren Sterlin, Ulcha Fergie Ulysse, Kathryn Sine, Oyin Alao, Jacqueline Lucia, Eric S. Lander, Todd R. Golub. The metastatic breast cancer project: Generating the clinical and genomic landscape of metastatic breast cancer through patient-partnered research [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr PD8-01.