Genomic and immunological tumor profiling identifies ... · Breast cancer is the second most common cancer in women. Inflammatory breast cancer (IBC) is the most aggressive and lethal
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Genomic and immunological tumor profiling identifies targetable pathways and extensive CD8+/PDL1+ immune infiltration in inflammatory breast cancer tumors Christopher A Hamm1,2,*, Diarmuid Moran1,3,*, Kakuturu Rao1,2, Patricia B. Trusk1, Karen Pry1,2, Mark Sausen4, Siân Jones4, Victor E. Velculescu5, Massimo Cristofanilli6, Sarah Bacus1,2,3 1Formerly Translational R&D Oncology Group, Quintiles, Westmont, IL, USA 2Currently: American Molecular Laboratories, Vernon Hills, IL, USA; 3Department of Pharmacology, University of Illinois at Chicago, Chicago, IL, USA; 4Personal Genome Diagnostics, Inc; Baltimore, MD, USA 5The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine; Baltimore, MD, USA, 6Department of Medical Oncology, Thomas Jefferson University Hospital, Philadelphia, PA, USA *Authors contributed equally to this work. Corresponding author(s): Christopher A Hamm ([email protected]), Diarmuid Moran ([email protected]). Financial support for this study was provided by Quintiles, and the study was conducted at Quintiles labs. Running Title: Genome and immune profiling of inflammatory breast cancer
Conflict of Interest Statement: V.E. Velculescu is a co-founder of Personal Genome Diagnostics and is a member of its Scientific Advisory Board and Board of Directors. V.E. Velculescu owns Personal Genome Diagnostics stock, which is subject to certain restrictions under University policy. The terms of these arrangements are managed by the Johns Hopkins University in accordance with its conflict-of-interest policies. The other authors do not have any potential conflicts of interest to disclose.
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on April 19, 2016; DOI: 10.1158/1535-7163.MCT-15-0353
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on April 19, 2016; DOI: 10.1158/1535-7163.MCT-15-0353
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on April 19, 2016; DOI: 10.1158/1535-7163.MCT-15-0353
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on April 19, 2016; DOI: 10.1158/1535-7163.MCT-15-0353
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on April 19, 2016; DOI: 10.1158/1535-7163.MCT-15-0353
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on April 19, 2016; DOI: 10.1158/1535-7163.MCT-15-0353
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on April 19, 2016; DOI: 10.1158/1535-7163.MCT-15-0353
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on April 19, 2016; DOI: 10.1158/1535-7163.MCT-15-0353
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on April 19, 2016; DOI: 10.1158/1535-7163.MCT-15-0353
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on April 19, 2016; DOI: 10.1158/1535-7163.MCT-15-0353
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on April 19, 2016; DOI: 10.1158/1535-7163.MCT-15-0353
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on April 19, 2016; DOI: 10.1158/1535-7163.MCT-15-0353
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on April 19, 2016; DOI: 10.1158/1535-7163.MCT-15-0353
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on April 19, 2016; DOI: 10.1158/1535-7163.MCT-15-0353
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on April 19, 2016; DOI: 10.1158/1535-7163.MCT-15-0353
amplified/HER3-mutant IBC genotype may promote cell proliferation through the downstream activation of the
PI3K/mTOR pathway, which suggests that HER-targeted therapies in combination with other HER/PI3K/mTOR therapies
should be further explored in IBC treatment. The iScore may serve as a surrogate biomarker of neo-antigen exposure to
the immune system. The iScore may also be a useful tool to predict neoantigen exposure in other tumor types,
however, a larger cohort of patients will be necessary to determine the clinical utility of the iScore in IBC and other
tumors. Given the robust immune component of IBC, the presence of PD-L1-positive IBC immune infiltrate suggests
that IBCs may benefit from therapies that disrupt PD-L1 signaling. Clinical studies will be required to further understand
the implications of each tumor background with respect to the proposed treatment options. Overall this study
highlights the importance of comprehensive tumor profiling that incorporates genomics, immunological analysis, and
other approaches to provide greater insight into the ideal strategy for personalized treatment in IBC and other cancers.
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Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on April 19, 2016; DOI: 10.1158/1535-7163.MCT-15-0353
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on April 19, 2016; DOI: 10.1158/1535-7163.MCT-15-0353
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on April 19, 2016; DOI: 10.1158/1535-7163.MCT-15-0353
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on April 19, 2016; DOI: 10.1158/1535-7163.MCT-15-0353
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on April 19, 2016; DOI: 10.1158/1535-7163.MCT-15-0353
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on April 19, 2016; DOI: 10.1158/1535-7163.MCT-15-0353
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on April 19, 2016; DOI: 10.1158/1535-7163.MCT-15-0353
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on April 19, 2016; DOI: 10.1158/1535-7163.MCT-15-0353
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on April 19, 2016; DOI: 10.1158/1535-7163.MCT-15-0353
Published OnlineFirst April 19, 2016.Mol Cancer Ther Christopher A Hamm, Diarmuid Moran, Kakuturu Rao, et al. infiltration in inflammatory breast cancer tumorstargetable pathways and extensive CD8+/PDL1+ immune Genomic and immunological tumor profiling identifies
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Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on April 19, 2016; DOI: 10.1158/1535-7163.MCT-15-0353