ABSTRACT

BACKGROUND: The standard recommendation for neoadjuvant therapy for human epidermal growth factor receptor-2 (HER2)-positive breast cancer patients is trastuzumab in combination with chemotherapy, but there is no current standard recommendation for appropriate chemotherapy regimens. This meta-analysis evaluated the efficacy and cardiac safety of the concurrent use of anti-HER2 targeted drugs and anthracycline-based neoadjuvant chemotherapy (NAC) for HER2-positive breast cancers.

METHODS: The pooled odds ratio (OR) rate for pathologic complete response (pCR), the pooled hazard ratio (HR) of overall survival (OS), and the left ventricular ejection fraction (LVEF) decline events were all calculated. Differences in efficacy, prognosis, and cardiac safety were compared between patients receiving an anthracycline-containing regimen (AB) and those treated with non-anthracycline-based (nAB) NAC.

RESULTS: A total of 1366 patients in 4 prospective and 3 retrospective studies were included in the meta-analysis. The pooled OR for pCR rate was 0.73 with a 95% confidence interval (CI) of 0.43 to 1.24 (P = .246). Subgroup analysis of low tumor burden cases showed no improvement in pCR rate for patients in the AB group compared with nAB, with the pooled OR rate being 0.73 with a 95% CI of 0.37 to 1.44 (P= .357). The 3-year OS rate was 95.63% and 95.54% in the AB and nAB groups, respectively, with no statistical difference (P= .157). There was a significant increase in the rate of LVEF decline of 19.07% in the AB group compared with 13.33% for the nAB group, with an HR of 1.62 and a 95% CI of 1.11 to 2.36 (P = .013).

CONCLUSIONS: The addition of anthracyclines did not improve pCR rates and survival after neoadjuvant and the increased cardiotoxicity of anthracyclines further limited their application. This study showed that it was feasible to use anti-HER2 drugs without anthracyclines in neoadjuvant therapy for HER2-positive breast cancer patients.

PMID:37744425 | PMC:PMC10515528 | DOI:10.1177/11795549231195293

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PubMed articles on: Cardio-Oncology

Galectin-3 contributes to acute cardiac dysfunction and toxicity by increasing oxidative stress and fibrosis in doxorubicin-treated mice

Int J Cardiol. 2023 Sep 21:131386. doi: 10.1016/j.ijcard.2023.131386. Online ahead of print.

ABSTRACT

BACKGROUND: Doxorubicin (DOX) leads to cardiovascular toxicity through direct cardiomyocyte injury and inflammation. We aimed to study the role of Galectin-3 (Gal-3), a β-galactosidase binding lectin associated with inflammation and fibrosis in DOX-induced acute cardiotoxicity in mice.

METHODS: Male C57 and Gal-3 knockout (KO) mice were given a single dose of DOX (15 mg/kg, i.p) or placebo. Serum creatine phosphokinase (CPK), lactate dehydrogenase (LDH), aspartate aminotransferase (AST) and cardiac thiobarbituric acid-reactive substance (TBARS) were measured at 3 days to assess cardiac injury and oxidative stress. Cardiac remodeling and function were studied by echocardiography and catheterization at 7 days. Myocardial fibrosis was quantified in picrosirius red stained slices.

RESULTS: Absence of Gal-3 tended to reduce the mortality after DOX. DOX significantly increased CPK, LDH, AST and TBARS while treated Gal-3 KO mice showed reduced injury and oxidative stress. After 7 days, adverse remodeling, fibrosis and dysfunction in treated-C57 mice were severely affected while those effects were prevented by absence of Gal-3.

CONCLUSION: In summary, genetic deletion of Gal-3 prevented cardiac damage, adverse remodeling and dysfunction, associated with reduced cardiac oxidative stress and fibrosis. Understanding the contribution of GAL-3 to doxorubicin-induced cardiac toxicity reinforces its potential use as a therapeutic target in patients with several cancer types.

PMID:37741348 | DOI:10.1016/j.ijcard.2023.131386

20:49

PubMed articles on: Cancer & VTE/PE

A case report: A patient rescued by VA-ECMO after cardiac arrest triggered by trigeminocardiac reflex after nasal surgery

Medicine (Baltimore). 2023 Sep 29;102(39):e35226. doi: 10.1097/MD.0000000000035226.

ABSTRACT

RATIONALE: Cardiac arrest (CA) caused by trigeminocardiac reflex (TCR) after endoscopic nasal surgery is rare. Hence, when a patient suffers from TCR induced CA in the recovery room, most doctors may not be able to find the cause in a short time, and standard cardiopulmonary resuscitation and resuscitation measures may not be effective. Providing circulatory assistance through venous-arterial extracorporeal membrane oxygenation (VA-ECMO) can help healthcare providers gain time to identify the etiology and initiate symptom-specific treatment.

PATIENT CONCERNS: We report a rare case of CA after endoscopic nasal surgery treated with VA-ECMO.

DIAGNOSES: We excluded myocardial infarction, pulmonary embolism, allergies, hypoxia, and electrolyte abnormalities based on the relevant examination results. Following a multidisciplinary consultation, clinical manifestation and a review of previous literature, we reasoned that the CA was due to TCR.

INTERVENTIONS: VA-ECMO was established to resuscitate the patient successfully during effective cardiopulmonary resuscitation.

OUTCOMES: ECMO was successfully evacuated a period of 190 minutes of therapy. The patient was discharged home on day 8.

LESSONS: TCR is notable during endoscopic nasal surgery. Our case indicates that CA in operating room is worth prolonged CCPR. The ideal time for ECPR implementation should not be limited within 20 minutes after CCPR.

PMID:37773828 | DOI:10.1097/MD.0000000000035226

20:49

PubMed articles on: Cardio-Oncology

Everolimus prevents doxorubicin-induced apoptosis in H9c2 cardiomyocytes but not in MCF-7 cancer cells: Cardioprotective roles of autophagy, mitophagy, and AKT

Toxicol In Vitro. 2023 Sep 21;93:105698. doi: 10.1016/j.tiv.2023.105698. Online ahead of print.

ABSTRACT

Cardiotoxicity is a severe side effect of the chemotherapeutic agent doxorubicin (DOX). We recently showed that DOX-induced cardiomyocyte apoptosis and death were attenuated through autophagy pre-induction. Herein, we assessed how the autophagy/mitophagy-inducing antitumor drug everolimus (EVL) affected DOX-induced cytotoxicity in the rat cardiomyocyte cell line H9c2 and human breast cancer cell line MCF-7. Apoptosis was assessed using annexin V assay. Autophagy and mitophagy were assessed using fluorescence assays. Cellular protein levels were determined using western blotting. Pretreatment with EVL (1 nM) before DOX exposure inhibited mammalian target of rapamycin (mTOR) activity, induced autophagy and mitophagy, and activated protein kinase B (AKT) in H9c2 cells. In mitochondria, DOX (1 μM) induced structural damage (decreased membrane potential and release of cytochrome c), increased superoxide levels, decreased apoptosis inhibitor Bcl-2, and increased apoptosis inducer Bax, leading to apoptosis and reduced viability in H9c2 cells. EVL pretreatment suppressed DOX-induced changes. EVL anti-apoptotic effects were inhibited by treatment with MK-2206, a selective AKT inhibitor. Furthermore, EVL suppressed DOX-induced cardiotoxicity through autophagy/mitophagy and AKT activation but did not attenuate DOX-induced apoptosis or reduction in viability in MCF-7 cells. Altogether, EVL can protect cardiomyocytes from DOX-induced apoptosis and toxicity without reducing DOX antitumor effects, allowing safer chemotherapy.

PMID:37739323 | DOI:10.1016/j.tiv.2023.105698

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PubMed articles on: Cancer & VTE/PE

Survey on the Knowledge and Management of Cancer-Associated Thrombosis (CAT) in Haemato-Oncology Patients with Thrombocytopenia among Haematologists and Haematology Residents in Nigeria

West Afr J Med. 2023 Sep 28;40(9):956-961.