ABSTRACT
WHAT IS KNOWN AND OBJECTIVE: Breast cancer is one of the leading causes of morbidity and mortality in women worldwide. In order to reduce the risks of its recurrence, endocrine therapies, such as tamoxifen and aromatase inhibitors are commonly administered. Despite having a similar efficacy in preventing breast cancer recurrence, these drugs differ in terms of instigating cardiovascular morbidities. Recent randomized controlled trials and cohort studies provide inconclusive evidence of the cardiovascular risks associated with the administration of these endocrine therapies. This present review and meta-analysis evaluates the comparative cardiovascular adverse event outcomes in breast cancer patients receiving tamoxifen and aromatase inhibitors. To evaluate the comparative cardiovascular adverse outcomes, such as venous thromboembolism, heart failure, angina, myocardial infarction and stroke in patients with breast cancer receiving tamoxifen and aromatase inhibitors. METHODS: A systematic search of the academic literature was performed according to the PRISMA guidelines across five databases, including Web of Science, EMBASE, CENTRAL, Scopus, and MEDLINE. A random-effect meta-analysis was conducted to compare the cardiovascular adverse events (i.e. venous thromboembolism, heart failure, angina, myocardial infarction, stroke) in breast cancer patients treated with tamoxifen and aromatase inhibitors. RESULTS AND DISCUSSION: From 993 studies, 20 eligible studies were identified, with 174,142 female breast cancer patients (mean age: 67.4 ± 3.8 years). A meta-analysis revealed insignificantly (p > 0.05) higher risks of venous thromboembolism (Odds ratio, 95% CI: 1.70, 0.91-3.18) in patients treated with tamoxifen as compared to aromatase inhibitors. We also observed insignificantly higher risks of stroke (0.93, 0.45-1.91), angina (0.77, 0.12-4.59), myocardial infarction (0.74, 0.30-1.79), and heart failure (0.81, 0.22-2.91) in patients receiving aromatase inhibitors as compared to tamoxifen. WHAT IS NEW AND CONCLUSIONS: The study provides evidence regarding the comparative cardiovascular adverse outcomes between breast cancer patients consuming tamoxifen and aromatase inhibitors. The study reports an insignificant increase in the events of stroke, angina, myocardial infarction, and heart failure in breast cancer patients treated with aromatase inhibitors as compared to tamoxifen. The study also reports that tamoxifen treatment is associated with an insignificant increase in the events of venous thromboembolism as compared to treatment with aromatase inhibitors.
Subject(s)
Breast Neoplasms , Cardiovascular Diseases , Heart Failure , Myocardial Infarction , Stroke , Venous Thromboembolism , Aged , Antineoplastic Agents, Hormonal/adverse effects , Aromatase Inhibitors/adverse effects , Breast Neoplasms/chemically induced , Breast Neoplasms/drug therapy , Cardiovascular Diseases/chemically induced , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/prevention & control , Female , Heart Failure/drug therapy , Humans , Middle Aged , Myocardial Infarction/chemically induced , Myocardial Infarction/drug therapy , Myocardial Infarction/epidemiology , Neoplasm Recurrence, Local/drug therapy , Stroke/drug therapy , Tamoxifen/adverse effects , Venous Thromboembolism/chemically induced , Venous Thromboembolism/drug therapyABSTRACT
Estrogen receptor (ER) is a nuclear hormone receptor and plays an important role in mediating the cellular effects of estrogen. ER can be classified into two receptors: estrogen receptor alpha (ERα) and beta (ERß), and the former is expressed in 50~80% of breast tumors and has been extensively investigated in breast cancer for decades. Excessive exposure to estrogen can obviously stimulate the growth of breast cancers primarily mediated by ERα, and thus anti-estrogen therapies by small molecules are of concern to clinicians and pharmaceutical industry in the treatment of ERα-positive breast cancers. Although a series of estrogen receptor modulators have been developed, these drugs can lead to resistance and side effects. Therefore, the development of small molecule inhibitors with high target specificity has been intensified. In this pursuit, an integrated computer-aided virtual screening technique, including molecular docking and pharmacophore model screening, was used to screen traditional Chinese medicine (TCM) databases. The compounds with high docking scores and fit values were subjected to ADME (adsorption, distribution, metabolism, excretion) and toxicity prediction, and ten hits were identified as potential inhibitors targeting ERα. Molecular docking was used to investigate the binding modes between ERα and three most potent hits, and molecular dynamic simulations were chosen to explore the stability of these complexes. The rank of the predicted binding free energies evaluated by MM/GBSA is consistent with the docking score. These novel scaffolds discovered in the present study can be used as critical starting point in the drug discovery process for treating ERα-positive breast cancer. Graphical abstract .