Biomedicines, Vol. 10, Pages 3170: Detection of BRCA1, and BRCA2 in Matched Tumor Tissue and Circulating Cell-Free DNA in Patients with Prostate Cancer in a Real-World Setting

Author Contributions

Conceptualization, T.R.M., V.M.T., N.A. and U.S.; Formal analysis, T.R.M., R.N., N.A. and U.S.; Investigation, T.R.M., V.M.T., R.N., G.G., N.S., N.T., K.K.S., D.G., B.L.M., D.S., N.A. and U.S.; Methodology, T.R.M., V.M.T., N.A. and U.S.; Visualization, T.R.M.; Writing—original draft, T.R.M., V.M.T., R.N., G.G., N.S., N.T., K.K.S., D.G., B.L.M., D.S., N.A. and U.S.; Writing—review and editing, T.R.M., V.M.T., R.N., G.G., N.S., N.T., K.K.S., D.G., B.L.M., D.S., N.A. and U.S. All authors have read and agreed to the published version of the manuscript.

Funding

This research received no external funding.

Institutional Review Board Statement

The study was conducted according to the guidelines of the Declaration of Helsinki, and approved by the Institutional Review Board of the University of Utah (IRB #67518, date of approval: 5 September 2013, last approved: 6 December 2022).

Informed Consent Statement

Patient consent was waived because it is retrospective, non-interventional study, and used anonymized data.

Data Availability Statement

The data generated in this study are not publicly available as they could compromise patient privacy but are available upon reasonable request from the corresponding author.

Conflicts of Interest

N.A. reports consultancy (lifetime association) to Astellas, AstraZeneca, Aveo, Bayer, Bristol Myers Squibb, Calithera, Clovis, Eisai, Eli Lilly, EMD Serono, Exelixis, Foundation Medicine, Genentech, Gilead, Janssen, Merck, MEI Pharma, Nektar, Novartis, Pfizer, Pharmacyclics, and Seattle Genetics. NA additionally reports institutional research funding from Astra Zeneca, Bavarian Nordic, Bayer, Bristol Myers Squibb, Calithera, Celldex, Clovis, Eisai, Eli Lilly, EMD Serono, Exelixis, Genentech, Glaxo Smith Kline, Immunomedics, Janssen, Medivation, Merck, Nektar, New Link Genetics, Novartis, Pfizer, Prometheus, Rexahn, Roche, Sanofi, Seattle Genetics, Takeda, and Tracon. U.S. reports consultancy to Astellas, Exelixis, Seattle Genetics, Imvax, AstraZeneca and Sanofi and research funding to institute from Janssen, Exelixis and Astellas/Seattle Genetics. B.L.M. is a paid consultant/advisor to Abbvie, Pfizer, AVEO oncology, Janssen, Astellas, Bristol-Myers Squibb, Clovis, Tempus, Merck, Exelixis, Bayer Oncology and Peloton Therapeutics. Huntsman Cancer Institute has received research funding from Exelixis (Inst), Bavarian-Nordic (Inst), Clovis (Inst), Genentech (Inst) and Bristol-Myers Squibb (Inst) on his behalf.

Figure 1. (A) Sankey diagram of all samples, the median and range for the time interval between each test is shown at the top. (B) Germline testing results, germline BRCA1/2 mutation (BRCA), not tested (NT), variant of uncertain significance (VUS), pathogenic variant (Path), negative result (Neg). (C) Sites for the samples with the metastatic samples broken down based on specific location. (D) patient selection workflow, copy number alterations (CNAs), BRCA mutations (BRCAm), BRCA wild-type (BRCAwt).

Figure 1. (A) Sankey diagram of all samples, the median and range for the time interval between each test is shown at the top. (B) Germline testing results, germline BRCA1/2 mutation (BRCA), not tested (NT), variant of uncertain significance (VUS), pathogenic variant (Path), negative result (Neg). (C) Sites for the samples with the metastatic samples broken down based on specific location. (D) patient selection workflow, copy number alterations (CNAs), BRCA mutations (BRCAm), BRCA wild-type (BRCAwt).

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Figure 2. (A) Timeline of detection for the 23 patients with BRCA mutations. Each grey bar represents one mutation with total length of the bar indicating the time from first diagnosis to last follow up or death, except for the reversion mutations. Note that many of the patients were de novo metastatic. (BG) Concordance tables for prostate (P), blood (B), and metastatic (M) samples showing the presence (+) or absence (−) of a BRCA mutation. (B) Prostate and blood, all samples. (C) Prostate and blood, without undetectable mutations. (D) Metastasis and blood, all samples. (E) Metastasis and blood, without undetectable mutations. (B) Prostate and metastasis, all samples.

Figure 2. (A) Timeline of detection for the 23 patients with BRCA mutations. Each grey bar represents one mutation with total length of the bar indicating the time from first diagnosis to last follow up or death, except for the reversion mutations. Note that many of the patients were de novo metastatic. (BG) Concordance tables for prostate (P), blood (B), and metastatic (M) samples showing the presence (+) or absence (−) of a BRCA mutation. (B) Prostate and blood, all samples. (C) Prostate and blood, without undetectable mutations. (D) Metastasis and blood, all samples. (E) Metastasis and blood, without undetectable mutations. (B) Prostate and metastasis, all samples.

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