ABSTRACT

Background Cancer therapy-related cardiac dysfunction (CTRCD) is an important treatment-limiting toxicity for patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer that adversely affects cancer and cardiovascular outcomes. Easy-to-use tools that incorporate readily accessible clinical variables for individual estimation of CTRCD risk are needed. Methods and Results From 2004 to 2013, 1440 patients with stage I to III HER2-positive breast cancer treated with trastuzumab-based therapy were identified. A multivariable Cox proportional hazards model was constructed to identify risk factors for CTRCD and included the 1377 patients in whom data were complete. Nine clinical variables, including age, race, body mass index, left ventricular ejection fraction, systolic blood pressure, coronary artery disease, diabetes, arrhythmia, and anthracycline exposure were built into a nomogram estimating risk of CTRCD at 1 year. The nomogram was validated for calibration and discrimination using bootstrap resampling. A total of 177 CTRCD events occurred within 1 year of HER2-targeted treatment. The nomogram for prediction of 1-year CTRCD probability demonstrated good discrimination, with a concordance index of 0.687. The predicted and observed probabilities of CTRCD were similar, demonstrating good model calibration. Conclusions A nomogram composed of 9 readily accessible clinical variables provides an individualized 1-year risk estimate of CTRCD among women with HER2-positive breast cancer receiving HER2-targeted therapy. This nomogram represents a simple-to-use tool for clinicians and patients that can inform clinical decision-making on breast cancer treatment options, optimal frequency of cardiac surveillance, and role of cardioprotective strategies.

PMID:37750581 | DOI:10.1161/JAHA.123.029465

13:56

PubMed articles on: Cardio-Oncology

When helping hurts: restricting cardiotoxicity of cancer therapeutics with accurate cardiovascular risk assessment works!

Eur J Prev Cardiol. 2023 Sep 25:zwad273. doi: 10.1093/eurjpc/zwad273. Online ahead of print.

NO ABSTRACT

PMID:37747453 | DOI:10.1093/eurjpc/zwad273

13:56

PubMed articles on: Cardio-Oncology

α-Bisabolol, a Dietary Sesquiterpene, Attenuates Doxorubicin-Induced Acute Cardiotoxicity in Rats by Inhibiting Cellular Signaling Pathways, Nrf2/Keap-1/HO-1, Akt/mTOR/GSK-3β, NF-κB/p38/MAPK, and NLRP3 Inflammasomes Regulating Oxidative Stress and Inflammatory Cascades

Int J Mol Sci. 2023 Sep 13;24(18):14013. doi: 10.3390/ijms241814013.

ABSTRACT

Cancer chemotherapy with doxorubicin (DOX) may have multiorgan toxicities including cardiotoxicity, and this is one of the major limitations of its clinical use. The present study aimed to evaluate the cardioprotective role of α-Bisabolol (BSB) in DOX-induced acute cardiotoxicity in rats and the underlying pharmacological and molecular mechanisms. DOX (12.5 mg/kg, single dose) was injected intraperitoneally into the rats for induction of acute cardiotoxicity. BSB was given orally to rats (25 mg/kg, p.o. twice daily) for a duration of five days. DOX administration induced cardiac dysfunction as evidenced by altered body weight, hemodynamics, and release of cardio-specific diagnostic markers. The occurrence of oxidative stress was evidenced by a significant decline in antioxidant defense along with a rise in lipid peroxidation and hyperlipidemia. Additionally, DOX also increased the levels and expression of proinflammatory cytokines and inflammatory mediators, as well as activated NF-κB/MAPK signaling in the heart, following alterations in the Nrf2/Keap-1/HO-1 and Akt/mTOR/GSK-3β signaling. DOX also perturbed NLRP3 inflammasome activation-mediated pyroptosis in the myocardium of rats. Furthermore, histopathological studies revealed cellular alterations in the myocardium. On the contrary, treatment with BSB has been observed to preserve the myocardium and restore all the cellular, molecular, and structural perturbations in the heart tissues of DOX-induced cardiotoxicity in rats. Results of the present study clearly demonstrate the protective role of BSB against DOX-induced cardiotoxicity, which is attributed to its potent antioxidant, anti-inflammatory, and antihyperlipidemic effects resulting from favorable modulation of numerous cellular signaling regulatory pathways, viz., Nrf2/Keap-1/HO-1, Akt/mTOR/GSK-3β, NF-κB/p38/MAPK, and NLRP3 inflammasomes, in countering the cascades of oxidative stress and inflammation. The observations suggest that BSB can be a promising agent or an adjuvant to limit the cardiac injury caused by DOX. Further studies including the role in tumor-bearing animals as well as regulatory toxicology are suggested.

PMID:37762315 | PMC:PMC10530367 | DOI:10.3390/ijms241814013

13:57

PubMed articles on: Cancer & VTE/PE

Risk of venous thromboembolism in patients undergoing gastric cancer surgery: a systematic review and meta-analysis

BMC Cancer. 2023 Oct 3;23(1):933. doi: 10.1186/s12885-023-11424-x.