Matches in SemOpenAlex for { <https://semopenalex.org/work/W4380149013> ?p ?o ?g. }
- W4380149013 abstract "Abstract Capturing the full complexity of the clinical experiences of metastatic breast cancer (MBC) patients treated in a variety of settings is needed to better understand this disease and develop new treatment modalities. Yet, challenges exist to establish and share a large MBC dataset that integrates genomic, clinical, and patient-reported data as it requires collecting information and samples from many geographically dispersed patients and institutions. We explored whether a patient-partnered research approach that uses online engagement could enable patients living across the United States and Canada to accelerate cancer research by sharing their samples, clinical information, and experiences. In collaboration with patients and patient advocates, the Metastatic Breast Cancer Project (MBCproject; www.mbcproject.org ) was developed and launched in October 2015. As of March 2020, 3,246 MBC patients who received treatment at ∼1,700 institutions had consented for the MBCproject, providing patient-reported information via surveys, as well as access to medical records and biological samples. Through the collection and analysis of tumor and germline samples, medical records, and patient-reported data, the MBCproject generates and publicly releases clinically-annotated genomic data on primary and metastatic tumor specimens on a recurring basis. Herein we describe the MBCproject cohort in detail and describe the clinico-genomic landscape of the MBCproject dataset. The complete dataset consists of whole exome sequencing (WES) for 379 tumors with matching germline from 301 patients, WES on germline samples from 377 patients, and transcriptome sequencing (RNA-seq) for 200 tumors from 141 patients, with clinical data from medical records and patient-reported information. A comparison of various clinical fields (diagnostic dates, tumor histology, tumor sites, treatments received) obtained from patient-reported data and the abstracted from medical records found a high degree of concordance, with multiple fields having over 90% concordance. Analysis of the somatic alterations in the 249 tumors taken after metastatic diagnosis found a significant enrichment of mutations in the cancer genes TP53 , PIK3CA , CDH1 , PTEN, AKT1, NF1 , and ESR1 , among others. Tumor evolutionary analysis of 14 patients with 3 or more samples identified oncogenic mutations in ESR1 , NF1 , and TP53 , genes associated with MBC and/or resistance to endocrine therapy. Analysis of germline samples identified pathogenic variants in the cancer-associated genes BRCA1, BRCA2 , ATM, and PALB2 . Comparing the frequency of pathogenic variants in patients diagnosed before/at or after the age of 40 years old, we found that the presence of these variants in BRCA1 or BRCA2 was enriched in the younger group compared to the older group (9.2% vs 2.5%, p=0.0089; two-sided Fisher exact test). Transcriptome sequencing identified putatively oncogenic in-frame fusions in cancer genes such as FANCD2 , FGFR3 , ESR1 , BRAF and NCOR1 . Analysis of tumor’s intrinsic molecular subtype (research-based PAM50) found a depletion of the Luminal A subtype in MBCproject compared to The Cancer Genome Atlas, and a switch in molecular subtype in 15 out of 35 patients with 2 or more samples. A case study of a patient with sequencing data from 4 tumor biopsies obtained during the course of their metastatic disease is presented. An integrated analysis of the clinical and multi-omic data from this patient identified distinct drivers of resistance to endocrine therapy in each of these tumors. The MBCproject clinico-genomic dataset is one of the largest available MBC patient cohorts This integrated dataset is poised for studying several understudied clinical cohorts (young women with breast cancer, de novo MBC), rare disease subtypes (e.g. lobular, metaplastic, extraordinary responders), biomarkers of response/resistance (e.g. CDK4/6 inhibitors), and real world patterns, among others, and will serve as an invaluable resource to accelerate discoveries." @default.
- W4380149013 created "2023-06-11" @default.
- W4380149013 creator A5001449157 @default.
- W4380149013 creator A5001689488 @default.
- W4380149013 creator A5001809112 @default.
- W4380149013 creator A5002821748 @default.
- W4380149013 creator A5003214660 @default.
- W4380149013 creator A5003341493 @default.
- W4380149013 creator A5009753638 @default.
- W4380149013 creator A5010075419 @default.
- W4380149013 creator A5011878961 @default.
- W4380149013 creator A5012427753 @default.
- W4380149013 creator A5015473831 @default.
- W4380149013 creator A5018390662 @default.
- W4380149013 creator A5019042448 @default.
- W4380149013 creator A5019116727 @default.
- W4380149013 creator A5020000955 @default.
- W4380149013 creator A5020748592 @default.
- W4380149013 creator A5021137036 @default.
- W4380149013 creator A5022943610 @default.
- W4380149013 creator A5024772264 @default.
- W4380149013 creator A5035026840 @default.
- W4380149013 creator A5042583769 @default.
- W4380149013 creator A5042886213 @default.
- W4380149013 creator A5046555824 @default.
- W4380149013 creator A5047450354 @default.
- W4380149013 creator A5047807989 @default.
- W4380149013 creator A5050531820 @default.
- W4380149013 creator A5053581028 @default.
- W4380149013 creator A5054052093 @default.
- W4380149013 creator A5060647012 @default.
- W4380149013 creator A5062493149 @default.
- W4380149013 creator A5063296619 @default.
- W4380149013 creator A5066062996 @default.
- W4380149013 creator A5067563791 @default.
- W4380149013 creator A5068721624 @default.
- W4380149013 creator A5069875959 @default.
- W4380149013 creator A5078538229 @default.
- W4380149013 creator A5083096188 @default.
- W4380149013 creator A5083775135 @default.
- W4380149013 creator A5088232181 @default.
- W4380149013 creator A5090814335 @default.
- W4380149013 creator A5091018775 @default.
- W4380149013 date "2023-06-10" @default.
- W4380149013 modified "2023-10-17" @default.
- W4380149013 title "The Metastatic Breast Cancer Project: leveraging patient-partnered research to expand the clinical and genomic landscape of metastatic breast cancer and accelerate discoveries" @default.
- W4380149013 cites W1999574084 @default.
- W4380149013 cites W2005895632 @default.
- W4380149013 cites W2009720434 @default.
- W4380149013 cites W2082887122 @default.
- W4380149013 cites W2088580309 @default.
- W4380149013 cites W2096283457 @default.
- W4380149013 cites W2103441770 @default.
- W4380149013 cites W2114843025 @default.
- W4380149013 cites W2119180969 @default.
- W4380149013 cites W2132619562 @default.
- W4380149013 cites W2149441684 @default.
- W4380149013 cites W2150757282 @default.
- W4380149013 cites W2169456326 @default.
- W4380149013 cites W2170490448 @default.
- W4380149013 cites W2172358623 @default.
- W4380149013 cites W2214074259 @default.
- W4380149013 cites W2276335691 @default.
- W4380149013 cites W2343368549 @default.
- W4380149013 cites W2344657883 @default.
- W4380149013 cites W2475362987 @default.
- W4380149013 cites W2561541049 @default.
- W4380149013 cites W2570752636 @default.
- W4380149013 cites W2590417095 @default.
- W4380149013 cites W2591810315 @default.
- W4380149013 cites W2616354594 @default.
- W4380149013 cites W2746672093 @default.
- W4380149013 cites W2782723462 @default.
- W4380149013 cites W2794280643 @default.
- W4380149013 cites W2796153225 @default.
- W4380149013 cites W2796208126 @default.
- W4380149013 cites W2891700678 @default.
- W4380149013 cites W2903143832 @default.
- W4380149013 cites W2906900419 @default.
- W4380149013 cites W2944287971 @default.
- W4380149013 cites W2946317931 @default.
- W4380149013 cites W2946401664 @default.
- W4380149013 cites W2969909201 @default.
- W4380149013 cites W2976898289 @default.
- W4380149013 cites W3000078203 @default.
- W4380149013 cites W3005073090 @default.
- W4380149013 cites W3015634062 @default.
- W4380149013 cites W3023297023 @default.
- W4380149013 cites W3045659462 @default.
- W4380149013 cites W3099862724 @default.
- W4380149013 cites W3107018254 @default.
- W4380149013 cites W3118931130 @default.
- W4380149013 cites W3124119591 @default.
- W4380149013 cites W3133997201 @default.
- W4380149013 cites W3145628054 @default.
- W4380149013 cites W3176308859 @default.
- W4380149013 cites W3181438909 @default.
- W4380149013 cites W4205170775 @default.
- W4380149013 cites W4220949103 @default.
- W4380149013 cites W4226272961 @default.