Cardiac complications associated with trastuzumab in the setting of adjuvant chemotherapy for breast cancer overexpressing human epidermal growth factor receptor type 2 – a prospective study

Abstract

IntroductionTrastuzumab, a recombinant humanized monoclonal antibody, is targeted against the external domain of the human epidermal growth factor receptor type 2 (HER2). It improves efficacy of HER2-positive breast cancer treatment. The authors present their experience with patients (pts) treated with trastuzumab in the aspects of cardiac complications.Material and methodsWe observed prospectively 253 women with early positive HER2 breast cancer treated with trastuzumab. Assessment of cardiovascular status, ECG and echocardiography was performed initially and every 3 months until 6th month during follow-up.ResultsCardiac complications developed in 52 pts (20.55%) and included: asymptomatic left ventricle dysfunction (43), symptomatic heart failure (6), new asymptomatic LBBB (1); new negative T-waves in ECG (2). There was a progressive decline in left ventricular ejection fraction (LVEF) during treatment. It was more enhanced in pts with cardiac complications. Following trastuzumab termination/discontinuation LVEF increased but at month 18 still remained significantly lower than initially in both groups (61.07 ±4.84 vs. 59.97 ±5.23 – no cardiac complications; p < 0.05; 58.14 ±4.08% vs. 53.08 ±5.74% – cardiac complications; p < 0.05). During 6-month follow-up 33 out of 46 pts experienced an improvement in left ventricular status. In 13 pts in whom trastuzumab was discontinued, it was restarted; 6 of them successfully completed total therapy. Univariate analysis revealed no association between any cardiovascular risk factor and the development of cardiotoxicity.ConclusionsOne out of five treated patients discontinues trastuzumab in an adjuvant setting due to cardiac complications. LV dysfunction is the most frequent. Routine cardiac monitoring should be obligatory.

Immunohistochemical evaluation of human epidermal growth factor receptor 2 and estrogen and progesterone receptors in invasive breast cancer in women

“…There are also works showing that in HER2-positive patients, survival and disease-free time were shorter than in patients lacking HER2 in the tumor regardless of the presence or absence of lymph node metastases [17]. In our study, there was no relationship between tumor size, lymph node status, and HER2 expression.…”

Antiproliferative and apoptotic activity of glycyrrhizinic acid in MCF-7 human breast cancer cells and evaluation of its effect on cell cycle, cell migration and m-TOR/PI3K/Akt signalling pathway

“…In conclusion, glycyrrhizinic acid inhibited MCF-7 human breast cancer cell growth by inhibiting colony formation, inducing apoptosis and sub-G1 cell cycle arrest, inhibiting cell invasion and targeting the m-TOR/PI3K/Akt signalling pathway. Several compounds that target the m-TOR/PI3K/ Akt pathway are promising anticancer agents [25,26]. We strongly believe that glycyrrhizinic acid may prove an important lead molecule.…”

Continuous Trastuzumab Therapy in Breast Cancer Patients With Asymptomatic Left Ventricular Dysfunction

“…Although the risk of heart failure during therapy is low, ranging from 1% to 4%, asymptomatic LVEF declines are more common, reported in 7%-19% of patients in clinical trials [2,5,6]. In clinical practice, rates of adverse cardiac events are considerably higher, particularly among older patients who often have underlying cardiovascular disease or risk factors [7][8][9][10].These patients are not well represented in clinical trials.…”