Cancer genetic disposition

Advances in early diagnosis and the development of treatments in breast cancer have led to improvements of disease-free and overall survival. Chemotherapy and targeted therapies induced cardiotoxicity is concerning, and the cardiovascular side effects can impact the quality of life and survival.

Cardiac risk factors should be assessed when deciding on treatment regimens for breast cancer.

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The second objective is establishing the proportion of patients who experienced reversible cardiotoxicity and clinical manifestations related cardiotoxicity, following treatment with trastuzumab and anthracyclines.

The analysis showed that adjuvant treatment was indicated in patients and that patients had metastatic disease, of which 44 patients were treated with trastuzumab in adjuvant setting and 67 were naive to treatment with trastuzumab.

Patients receveing trastuzumab had the following risk factors for cardiotoxicity: increased body mass index, smoking, sedentary, high cholesterol, high blood pressure, diabetes. The study results showed that administering trastuzumab to women with these cardiovascular risk factors led to increased cardiotoxicity and the reduction of LVEF, requiring temporary interruption of trastuzumab.

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Early recognition of cardiac toxicity can lead to improvement in cardiac survival and patient outcomes. The focus of cancer genetic disposition review was to summarize the cancer therapy agents most often associated with cardiovascular side effects, highlighting the risk factors that can be improved and strategies for surveillance and prevention. Early identification of individuals at risk and monitoring patients during chemotherapy are very important, and they can facilitate early intervention with cardioprotective medications or adjustments to the chemotherapy regimen.

Avansul în diagnosticul precoce şi dezvoltarea tratamentelor în cancerul de sân au condus la îmbunătăţirea supravieţuirii fără semne de boală şi a supravieţuirii globale.

Cancer genetic disposition. Traducere "predispoziția" în engleză

Cardiotoxicitatea indusă de chimioterapie şi de terapiile ţintite este importantă, iar efectele adverse pot afecta calitatea vieţii şi supravieţuirea. Factorii de risc cardiac ar trebui cuantificaţi la momentul alegerii seriei de chimioterapie pentru cancerul de sân.

Obiectivul secundar este stabilirea proporţiei de paciente care au prezentat cardiotoxicitate reversibilă şi manifestări clinice legate de aceasta, consecutiv tratamentului cu trastuzumab şi antraciclină. Analiza a arătat că tratamentul adjuvant a fost indicat la de paciente şi că paciente aveau boală metastatică, din care 44 erau tratate cu TR în adjuvantă şi 67 erau TR naive.

Cardiotoxicitatea la pacientele cu cancer de sân

Pacientele care au primit TR aveau următorii factori de risc: indice de masă corporal crescut, fumătoare, sedentare, colesterol mărit, tensiune arterială crescută, diabet. O pacientă aflată în tratament cu TR a dezvoltat toxicitate ireversibilă.

Acest studiu a arătat că administrarea de TR la femeile cu aceşti factori de risc a crescut cardiotoxicitatea şi reducerea fracţiei de ejecţie a ventriculului stâng, necesitând întreruperea temporară a administrării de TR. Recunoaşterea precoce a toxicităţii cardiace poate conduce la îmbunătăţirea supravieţuirii şi a rezultatelor obţinute.

cancer genetic disposition

Ţinta acestui studiu a fost să sumarizeze efectele adverse cardiace întâlnite cel mai frecvent în tratamentul cancerului, subliniind factorii de risc care pot fi amelioraţi şi strategiile pentru urmărire şi prevenţie. Identificarea precoce a pacientelor expuse la acest risc şi monitorizarea lor în cursul chimioterapiei sunt foarte importante şi pot facilita intervenţia timpurie cu agenţi cardioprotectori sau ajustarea regimului de chimioterapie.

Complications of antineoplastic treatments can occur and should be carefully evaluated.

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Aromatase inhibitors are associated with viermi revizuirile tratamentului lor increased risk of osteoporosis, tamoxifen is associated with uterine cancer and chemotherapy is associated with myelodysplasia cancer genetic disposition secondary leukemia. Furthermore, long-term cardiac toxicity is an important issue in breast cancer patients.

Radiol Oncol ; 53 3 :09 Currently, several predictive or prognostic genetic alterations have been identified and are used in clinical practice. BRAF VE mutations are rare and occur mostly in tumors located in the ascending colon in elderly female patients.

Chemotherapy-induced cardiotoxicity is concerning. Certain antineoplastic treatments like anthracyclines and targeted cancer genetic disposition are known to be cardiotoxic Cardiovascular side effects can impact the quality of life and survival. The most common side effects of antineoplastic treatment include vasospastic and thromboembolic ischemia, arterial hypertension, arrhythmia, cardiac dysfunction and heart failure There are two types of cardiotoxicity: type I cardiotoxicity, seen with anthracyclines caused by free radical formation that leads to oxidative stress and myofibrillar disorganizationthat is dose-related and considered irreversible, and type II cardiotoxicity, seen with the use of trastuzumab, that does not include ultrastructural abnormalities and is considered reversible with treatment discontinuation and does not relate to doses.

The difference between type I and type II is complicated.

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Studies have shown improvement in anthracycline-induced cardiac dysfunction with heart failure HF therapy, while other studies have shown irreversible fibrosis on magnetic resonance imaging in patients treated with trastuzumab Cardiovascular risk factors are the history of hypertension, diabetes, known coronary artery disease and cardiotoxicity of anticancer therapy. Known risk factors for trastuzumab-associated cardiac toxicity include a lower screening left ventricle ejection fraction LVEF and a lower post-anthracycline LVEF.

Alternative less cardiotoxic regimens should be considered, if the patient presents a high cardiac risk, with frequently monitoring cardiac function when cardiotoxic drugs cannot be avoided 2,5.

cancer genetic disposition

Risk factors for cardiac toxicity include genetic predisposition, very young or old age, female gender, higher single dose, intravenous bolus administration, previous or concurrent mediastinal radiation therapy, and combina­tion with alkylating or antimicrotubule chemotherapeutics.

Patients with underlying traditional cardiac risk factors such as hypertension, diabetes mellitus, hyperlipidemia, smoking history and known coronary artery disease also have increased risk 3,5 Figure 1. Type I cardiotoxicity Anthracyclines, like doxorubicin and epirubicin, are used in the treatment of breast cancer.

They are cancer genetic disposition agents and their mechanism includes intercalation into nuclear DNA to impair protein synthesis, production of reactive oxygen species and inhibition of topoisomerase II to inhibit DNA repair.

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Anthracyclines cause DNA damage and formation of reac­tive oxygen species, they induce the intracellular accumulation of iron and form complexes with it, further inducing the production of free oxygen radicals.

These mechanisms can lead to other cellular alterations changes in calcium homeostasis and abnormalities of the contractile apparatus.

Doxorubicin can cause death of cardiac cells and thus affecting cardiac structure and function.


The alteration of cardiac fibroblasts activity and the turnover of the myocardial extracellular matrix is a hypothesis sustained by the presence of fibrosis that has been observed in hearts that had been exposed to doxorubicin 3,5, In an article by Oliveira PJ et al. In contrast, atenolol ATa beta-adrenergic receptor antagonist lacking antioxidant properties, preserved phosphate energy charge, but failed to protect against any of the indexes of doxorubicin-induced oxidative mitochondrial toxicity 7.

cancer genetic disposition

Taxanes, such as paclitaxel and docetaxel, used in the treatment of advanced breast cancer, are antimicrotubule agents that bind to tubulin, cancer genetic disposition cell division, and have been associated with early LVD and HF. Paclitaxel causes massive histamine release that may lead to conduction disturbances and arrhythmias. Heart failure incidence associated with taxanes is relatively low 3,5, In HER2-positive breast cancer, the addition of trastuzumab prolongs overall survival in both early stage and metastatic disease.

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The interference in this pathway may explain the mechanism of cardiotoxicity. Trastuzumab can cause cardiac dysfunction in a number of patients and is increased when is coadministered with anthracyclines 3,5.

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The cardiac dysfunction induced by trastuzumab arises from impairment of contractility and not from the death of myocytes. The cardiac function is likely to recover within months and there is evidence that it is relatively safe to readminister trastuzumab after it has been discontinued and the myocardial function returned to baseline 1,3,5,9, The results of the study published by Gómez Peña validated the role of this polymorphism as a predictor of the cardiac toxicity of trastuzumab in breast cancer patients.

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The results of a study published in by Edith A. Older age, lower registration LVEF and antihypertensive medications are associated with increased risk of cardiac dysfunction in patients receiving trastuzumab following AC The combination of trastuzumab with other agents such as lapatinib and pertuzumab to increase the efficacy comes with the potential of supplementary cardiotoxicity Pertuzumab is a more recent anti-HER2 antibody that binds to the viermele inimii vă arată II of the receptor and interferes with the formation of ligand induced HER2 heterodimers.

A third HER2-targeting agent is lapatinib, a small molecule inhibitor of the intracellular tyrosine kinase domain of HER2 that affects both ligand triggered and ligand-independent HER2 signaling. Lapatinib seems to be less toxic than trastuzumab. Data about the toxicity of pertuzumab are limited 3,5,13, A meta-analysis published by Valachis A provides evidence supporting comparable cancer genetic disposition toxicity between anti-HER2 combination therapy and anti-HER2 monotherapy - overall incidence results for congestive heart failure in the combined anti-HER2 therapy and the anti-HER2 monotherapy were 0.

The incidence of LVEF decline was 3.

[Genetic Susceptibility to Cancer]

Trastuzumab emtansine TDM1 is an antibody-drug conjugate comprising the cytotoxic agent DM1, a stable linker and trastuzumab. TDM1 has shown clinically relevant activity in the treatment of HER2-positive breast cancer patients after progression on trastuzumab and taxane based therapy, both in the second line treatment setting and after early relapse on adjuvant trastuzumab therapy, with favorable safety and tolerability profile. A new clinical trial with TDM1 showed a median follow-up of Four patients 2.

Neuregulin binds to HER4 receptors which dimerize with HER2 receptors and increase several survival pathways in the myocardium.