@article{d4c62d4b0f454361b9b2522defc12c6e,
title = "Myocardial infarction accelerates breast cancer via innate immune reprogramming",
abstract = "Disruption of systemic homeostasis by either chronic or acute stressors, such as obesity1 or surgery2, alters cancer pathogenesis. Patients with cancer, particularly those with breast cancer, can be at increased risk of cardiovascular disease due to treatment toxicity and changes in lifestyle behaviors3–5. While elevated risk and incidence of cardiovascular events in breast cancer is well established, whether such events impact cancer pathogenesis is not known. Here we show that myocardial infarction (MI) accelerates breast cancer outgrowth and cancer-specific mortality in mice and humans. In mouse models of breast cancer, MI epigenetically reprogrammed Ly6Chi monocytes in the bone marrow reservoir to an immunosuppressive phenotype that was maintained at the transcriptional level in monocytes in both the circulation and tumor. In parallel, MI increased circulating Ly6Chi monocyte levels and recruitment to tumors and depletion of these cells abrogated MI-induced tumor growth. Furthermore, patients with early-stage breast cancer who experienced cardiovascular events after cancer diagnosis had increased risk of recurrence and cancer-specific death. These preclinical and clinical results demonstrate that MI induces alterations in systemic homeostasis, triggering cross-disease communication that accelerates breast cancer.",
author = "Koelwyn, {Graeme J.} and Newman, {Alexandra A.C.} and Afonso, {Milessa S.} and {van Solingen}, Coen and Corr, {Emma M.} and Brown, {Emily J.} and Albers, {Kathleen B.} and Naoko Yamaguchi and Deven Narke and Martin Schlegel and Monika Sharma and Shanley, {Lianne C.} and Barrett, {Tessa J.} and Karishma Rahman and Valeria Mezzano and Fisher, {Edward A.} and Park, {David S.} and Newman, {Jonathan D.} and Quail, {Daniela F.} and Nelson, {Erik R.} and Caan, {Bette J.} and Jones, {Lee W.} and Moore, {Kathryn J.}",
note = "Funding Information: Tissue sectioning and histological analyses were provided by the New York University (NYU) Langone{\textquoteright}s Experimental Pathology Research Laboratory. Cell sorting/flow cytometry technologies were provided by NYU Langone{\textquoteright}s Cytometry and Cell Sorting Laboratory, which is supported in part by grant P30CA016087 from the National Institutes of Health/National Cancer Institute. This work was supported by funding from the National Institutes of Health (R35HL135799 to K.J.M., P01HL131478 and P01HL131481 to K.J.M. and E.A.F., T32HL098129 to C.v.S., K23HL125991 to J.D.N., R01CA234025 to E.R.N., R01CA129059 to B.J.C. and R01HL132073 to D.S.P.); NYU Cancer Institute Center Support Grant NCIP30CA16087; NYU Shared Instrumentation Grant S10 OD021747; the Memorial Sloan Kettering Cancer Center Support Grant/ Core Grant (P30 CA008748)), the American Heart Association (19CDA34630066 to C.v.S., 19POST34380010 to M.S., 18CDA34110203 to T.J.B. and 20POST35080180 to N.Y.), the Canadian Institutes of Health Research (Doctoral Foreign Study Award to G.J.K. and PJT159742 to D.F.Q.), AKTIV Against Cancer (L.W.J.) and the Susan G. Komen Foundation (CCR18548032 to D.F.Q.). D.F.Q. is also supported by the Brain Tumor Funders{\textquoteright} Collaborative, Canada Foundation for Innovation and a Tier II Canada Research Chair in tumor microenvironment research. Publisher Copyright: {\textcopyright} 2020, The Author(s), under exclusive licence to Springer Nature America, Inc.",
year = "2020",
month = sep,
day = "1",
doi = "10.1038/s41591-020-0964-7",
language = "English (US)",
volume = "26",
pages = "1452--1458",
journal = "Nature Medicine",
issn = "1078-8956",
publisher = "Nature Publishing Group",
number = "9",
}