Arterial Stiffness: Effects of Anticancer Drugs Used for Breast Cancer Women

Abstract

Purpose: It is well known that anticancer drugs used for treating breast cancer can cause cardiac toxicity, and less is known about vascular toxicity. The aim of this study was to assess subclinical vascular effects of anthracyclines and trastuzumab (TRZ) in women treated for breast cancer.Methods: We enrolled 133 female patients with breast cancer undergoing adjuvant treatment with anthracycline-containing chemotherapy (CT) followed by taxane (paclitaxel/docetaxel) + TRZ. Patients underwent a standard echocardiography including measurement of left ventricular ejection fraction and global longitudinal strain at baseline and at follow-up. Vascular toxicity was evaluated by measuring brachial blood pressure (BP) and arterial stiffness indices (pulse wave velocity and Beta stiffness index) at T0 (baseline), T1 (3 months), T2 (6 months), and T3 (12 months).Results: Arterial stiffness indices were significantly increased at T1 in patients treated with anthracycline-containing CT (PWV 5.5 m/s IQR 5.15–6.4 at T0 vs. PWV 6.7 m/s IQR 5.6–7.2 at T1, p < 0.05; Beta index PWV 6.7 IQR 5.25–6.65 at T0, PWV 8.35 IQR 6.5–10.15 at T1, p < 0.05) but not at T2 and T3, when treatment with anthracyclines was stopped and patients were under treatment with taxane and TRZ. Blood pressure values did not significantly change during follow-up.Conclusion: Changes in arterial stiffness parameters occur early after starting treatment with anthracyclines, and they seem to be reversible if anthracycline treatment is stopped. These changes are not influenced by blood pressure values modifications. Therefore, in breast cancer women, anthracyclines seem to cause early reversible subclinical vascular injury.

Doxorubicin Impairs Smooth Muscle Cell Contraction: Novel Insights in Vascular Toxicity

“…It has been recently recognised that DOX impairs vascular function [ 11 , 12 , 13 , 14 , 19 ], yet the exact mechanisms are not fully elucidated yet. While there is consensus about the detrimental effects of DOX on endothelium-dependent vasodilation [ 19 , 20 , 21 , 22 ], several studies have reported conflicting results on VSMC contraction [ 23 , 24 , 25 ].…”

“…Epidemiological studies point towards accelerated vascular ageing in childhood cancer survivors, as evidenced by a higher incidence of atherosclerosis and hypertension [ 8 , 9 , 10 ]. Moreover, several studies have demonstrated that DOX increases arterial stiffness in cancer patients, both during and after treatment [ 11 , 12 , 13 , 14 ]. Arterial stiffness is associated with an increased risk of cardiovascular events and mortality, as it impacts arterial pressure, cardiac performance and perfusion [ 15 , 16 , 17 ].…”

New Insights on the Toxicity on Heart and Vessels of Breast Cancer Therapies

“…However, other cell types, such as endothelial cells, cardiac progenitor cells and cardiac fibroblasts, have been identified as potential additional targets, creating a more complex scenario in the pathogenesis of anthracycline-induced cardiotoxicity (Figure 1). Moreover, Novo et al [30] demonstrate an increase in arterial stiffness in patients treated with anthracyclines. Indeed, anthracycline-induced endothelial vascular damage might provoke structural acute vascular changes through the alterations of the vascular matrix and by interfering with the endothelial regulation of vascular smooth muscle cell tone by reducing nitric oxide synthesis.…”

Time-Dependent Effect of Anthracycline-Based Chemotherapy on Central Arterial Stiffness: A Systematic Review and Meta-Analysis

“…All studies were published between 2010 and 2021 and included patients with solid tumors, such as breast cancer or sarcoma (35)(36)(37)(38)(39)(40), or hematologic malignancies, such as lymphoma and leukemia (35,36,39,(41)(42)(43), or a combination thereof (35,36,39). All studies were prospective with data provided from before treatment as well as after a follow-up period between 1 and 14 months (Figure 2).…”

“…Therefore, the effect of cancer itself, presence of CV risk factors or other confounding treatments and comorbidities could not be identified. Secondly, except for two studies (40,42), they were based on small numbers of participants, which explains the large CIs of some of the studies. Another limitation of this meta-analysis is that the assumption of a normal distribution has been made for PWV in the study by Novo et al,(40) even though data was indicated as median (IQR).…”