Cardiac toxicity associated with anthracycline‐containing chemotherapy in older women with breast cancer

Abstract

Objective To identify the autoantigen recognized by the autoantibody that is associated with clinically amyopathic dermatomyositis (C‐ADM) and rapidly progressive interstitial lung disease (ILD). Methods An anti–CADM‐140 antibody–positive prototype serum sample was used to screen a HeLa cell–derived complementary DNA (cDNA) library. Selected cDNA clones were further evaluated by immunoprecipitation of their in vitro–transcribed and in vitro–translated products using anti–CADM‐140 antibody–positive and anti‐CADM‐140 antibody–negative sera. The lysates of COS‐7 cells transfected with the putative antigen were similarly tested. An enzyme‐linked immunosorbent assay (ELISA) to detect the anti–CADM‐140 antibody was established using a recombinant CADM‐140 antigen, and its specificity and sensitivity for C‐ADM and rapidly progressive ILD were assessed in 294 patients with various connective tissue diseases. Results By cDNA library screening and immunoprecipitation of in vitro–transcribed and in vitro–translated products, we obtained a cDNA clone encoding melanoma differentiation–associated gene 5 (MDA‐5). The anti–CADM‐140 antibodies in patients' sera specifically reacted with MDA‐5 protein expressed in cells transfected with full‐length MDA‐5 cDNA, confirming the identity of MDA‐5 as the CADM‐140 autoantigen. The ELISA, using recombinant MDA‐5 protein as the antigen, showed an analytical sensitivity of 85% and analytical specificity of 100%, in comparison with the “gold standard” immunoprecipitation assay, and was useful for identifying patients with C‐ADM and/or rapidly progressive ILD. Conclusion Given that RNA helicase encoded by MDA‐5 is a critical molecule involved in the innate immune defense against viruses, viral infection may play an important role in the pathogenesis of C‐ADM and rapidly progressive ILD. Moreover, our ELISA using recombinant MDA‐5 protein makes detection of the anti–CADM‐140 antibody routinely available.

Rationale for setting up a cardio-oncology unit: our experience at Mayo Clinic

“…[19][20][21][22][23][24][25]. There is also radiotherapy that has an all-inclusive involvement of the heart (myocardium, pericardium, valves and coronary arteries) [26] and can affect extra cardiac structures such as the great vessels where accelerated atherosclerosis can occur [27]. However, a reduction in left ventricular ejection fraction (LVEF) and subsequent development of CHF has drawn most of the attention among physicians.…”

Cardiac risk associated with the receipt of anthracycline and trastuzumab in a large nationwide cohort of older women with breast cancer, 1998–2005

“…Cardiotoxicity has been well documented to be associated with the use of anthracycline-containing chemotherapy from both clinical trials and observational studies [1][2][3][4][5]. Cardiotoxicity may occur either immediately at the time of drug administration, or months to years after treatment.…”

Performance of Claims-based Algorithms for Identifying Heart Failure and Cardiomyopathy Among Patients Diagnosed With Breast Cancer

“…Conversely, concerns about the possibility of chemotherapy-induced cardiotoxicity may result in overcoding of HF/CM. Previously published claims-based data analyses investigating cardiotoxicity among breast cancer patients have not validated their use of administrative codes, 16–18 and consequently have drawn criticism. 19 …”