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Review
. 2012 Dec 4;126(23):2749-63.
doi: 10.1161/CIRCULATIONAHA.112.100560.

Cancer therapy-induced cardiac toxicity in early breast cancer: addressing the unresolved issues

Michel G Khouri  1 , Pamela S Douglas, John R Mackey, Miguel Martin, Jessica M Scott, Marielle Scherrer-Crosbie, Lee W Jones
Affiliations
Review

Cancer therapy-induced cardiac toxicity in early breast cancer: addressing the unresolved issues

Michel G Khouri et al. Circulation. .
No abstract available

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Conflict of interest statement

Conflict of Interest Disclosures: None.

Figures

Figure 1
Figure 1
Cardiovascular Disease, Detection, Prevention and Treatment in Early Breast Cancer. A schematic representation describing the continuum of breast cancer treatment, cardiac toxicity and eventual development of cardiovascular disease, in particular, heart failure. Cancer occurs in the setting of the patient’s baseline health and risk factors profile. With the administration of potentially cardiac toxic therapies, surveillance diagnostic strategies may be adopted; others have proposed ‘primordial’ preventive treatment of all patients. A number of biomarker strategies have been assessed to detect subclinical cardiac toxicity; ‘primary’ preventative treatment has also been proposed. Once there is clear clinical evidence of cardiac toxicity (i.e., ACC/AHA Stage B heart failure), imaging and biomarkers may help to guide treatment; ‘secondary’ prevention is recommended to prevent development of symptomatic heart failure and cardiovascular disease. Finally, in those with overt heart failure, standard heart failure treatment is needed to reduce cardiovascular mortality. ACE indicates angiotensin converting enzyme; CV, cardiovascular; LVEF, left ventricular ejection fraction. ↓ indicates decline.
Figure 2
Figure 2
Mechanisms underlying anthracycline-induced cardiac toxicity. Anthracycline-induced generation of oxidative stress is a central mediator of: 1) accelerated myofilament apoptosis via upregulation of p53 pathway and iNOS, 2) suppression of myofilament protein synthesis via inhibition of CPCs and GATA-4, 3) calcium overload resulting in ultrastructural changes to myocytes, 4) alterations in cardiac energy metabolism via downregulation of AMPK. These changes lead to myocardial dysfunction and ultimately heart failure. Adapted from Scott et al. AMPK indicates AMP-activated protein kinase; CPCs, cardiac progenitor cells; iNOS, inducible nitric oxide synthase.
Figure 3
Figure 3
Mechanisms underlying molecularly targeted therapeutics-induced cardiac toxicity. Inhibition of Nrg1/ErbB receptors with HER2-directed therapies impacts numerous signaling pathways resulting in 1) suppression of myofilament protein synthesis via the PI3K-Akt pathway, 2) suppression of protein hypertrophy via the MAPK pathway, 3) suppression of cell survival via Src/Fak pathway, 4) upregulation of protein degradation via FOXO signaling. Fak indicates focal adhesion kinase; MAPK, mitogen-activated protein kinase; NO, nitric oxide; Nrg1, neuregulin-1β; PI3K, phosphatidylinositol 3-kinase.
See this image and copyright information in PMC

References

    1. Howlader N, Noone AM, Krapcho M, Neyman N, Aminou R, Altekruse SF, Kosary CL, Ruhl J, Tatalovich Z, Cho H, Mariotto A, Eisner MP, Lewis DR, Chen HS, Feuer EJ, Cronin KA, editors. SEER Cancer Statistics Review, 1975–2009 (Vintage 2009 Populations) National Cancer Institute; Bethesda, MD: Apr, 2012. [Accessed June 29, 2012]. http://seer.cancer.gov/csr/1975_2009_pops09/, based on November 2011 SEER data submission, posted to the SEER web site.
    1. Patnaik JL, Byers T, Diguiseppi C, Dabelea D, Denberg TD. Cardiovascular disease competes with breast cancer as the leading cause of death for older females diagnosed with breast cancer: A retrospective cohort study. Breast Cancer Res. 2011;13:R64. - PMC - PubMed
    1. Hooning MJ, Botma A, Aleman BM, Baaijens MH, Bartelink H, Klijn JG, Taylor CW, van Leeuwen FE. Long-term risk of cardiovascular disease in 10-year survivors of breast cancer. J Natl Cancer Inst. 2007;99:365–375. - PubMed
    1. Von Hoff DD, Layard MW, Basa P, Davis HL, Jr, Von Hoff AL, Rozencweig M, Muggia FM. Risk factors for doxorubicin-induced congestive heart failure. Ann Intern Med. 1979;91:710–717. - PubMed
    1. Swain SM, Whaley FS, Ewer MS. Congestive heart failure in patients treated with doxorubicin: A retrospective analysis of three trials. Cancer. 2003;97:2869–2879. - PubMed

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