Abstract
Te study involved 43 patients with newly diagnosed breast cancer (BC) (II-III stage) with overexpression of HER2; median age 50 (40;57) years. All patients underwent neoadjuvant drug therapy with antracyclines, taxanes and trastuzumab followed by surgery, radiation and hormone therapy according to the indications. Before anticancer therapy the general clinical examination was conducted and lipid profle, plasma lipoprotein (a) [Lp(a)] level, titres of autoantibodies IgM and IgG to lipoproteins and their oxidized derivatives were estimated. Te vascular wall stiffness (pulse wave velocity on the carotid-femoral (PWVcf) and shoulder-ankle (PWVsa) segments, the central pressure, carotid intima-media thickness (CIMT) and the degree of stenosis of the brachiocephalic arteries) were determined at baseline and at each stage of anticancer therapy. Te atherosclerosis progression was determined if the new stenosis (≥15%) or increase of preexisting stenosis (≥5%) were revealed; CIMT increase ≥ 0.1 mm. Te parameters of cellular immunity (peripheral blood lymphocyte phenotyping via direct immunofluorescence and flow cytometry), lipid spectrum parameters, serum concentration of Lp (a), autoantibodies IgM and IgG against lipoproteins and their oxidized derivatives, as well as PWVсf and PWVsa were assessed in 17 BC patients before the onset of neoadjuvant therapy and in 20 healthy women. BC patients and healthy women were comparable in traditional cardiovascular risk factors but differed in PWVsa and PWVcf levels (p<0.05). In BC patients the activation of T-cell immunity with the stimulation of both subpopulations with pro-inflammatory and regulatory properties was observed (p<0.05). Te direct correlations between the content of activated T-lymphocytes (T-act), T-helpers (T) 1 and PWVsa (p<0.05), as well as T-act, T1 and T2 and PWVcf (p<0.05) were revealed in the general group. Te decrease of systolic blood pressure (SBP), central SBP (SBPc), central diastolic blood pressure (DBPc), PWVcf and PWVsa levels accompanied with a temporary heart rate increase were observed during anticancer therapy; SBP, SBPc, PWVcf levels restored by the end of the follow-up period. Te CIMT increase was detected in 22 (51%), and the atherosclerosis progression in 26 (60%) BC patients during anticancer therapy. Lp (a) level above 12.8 mg/dl was associated with CIMT increase (p<0.05). Age > 48 years and radiation therapy were risk factors for CIMT increase and atherosclerosis progression (p<0.05), respectively. Te vascular stiffness is increased in BC patients, which is associated with the activation of effector subpopulations of T-lymphocytes and the elevation of circulating level of both pro-atherogenic and anti-atherogenic T-cells. Te level of Lp (a) above 12.8 mg/dl is associated with atherosclerosis progression, which requires further research. Age and radiation therapy are the risk factors for atherosclerosis progression during anticancer therapy.
Highlights
Возможности ранней диагностики и совершенствующиеся подходы к лечению приводят к неуклонному росту числа пациентов, перенесших онкологическое заболевание
Комплексная оценка состояния сосудистой стенки может иметь важное клиническое значение как на этапе первичного клинического обследования онкобольного, так и для мониторинга состояния сердечно-сосудистой системы в процессе проведения противоопухолевой терапии и после ее окончания
Kalábová H, Melichar B, Ungermann L, Doležal J, Krčmová L, Kašparová M et al Intima-media thickness, myocardial perfusion and laboratory risk factors of atherosclerosis in patients with breast cancer treated with anthracycline-based chemotherapy
Summary
Cardiovascular toxicity is one of the important problems of clinical oncology. Atherosclerosis progression was demonstrated in patients with cancer and chemotherapy. Комплексная оценка состояния сосудистой стенки может иметь важное клиническое значение как на этапе первичного клинического обследования онкобольного, так и для мониторинга состояния сердечно-сосудистой системы в процессе проведения противоопухолевой терапии и после ее окончания. Целью настоящего исследования явилось изучение состояния сосудистой стенки и определение предикторов развития атеросклероза брахиоцефальных артерий в процессе противоопухолевой терапии у больных РМЖ. У 17 больных РМЖ до начала неоадъювантной терапии и 20 здоровых женщин добровольцев без анамнеза сердечно-сосудистых и онкологических заболеваний были оценены показатели клеточного иммунитета, показатели липидного спектра, концентрация Лп(а) и уровень специфических аутоантител классов IgM и IgG против апоВ100‐содержащих липопротеидов и их окисленных модификаций, а также СПВпл и СПВкф. У больных РМЖ отмечалась активация Т-клеточного иммунитета со стимуляцией субпопуляций как с провоспалительными (Тх1, Тх2, Тх17, Тх-акт), так и с регуляторными свойствами Содержание показателей клеточного иммунитета у больных РМЖ и здоровых женщин: CD4+CD25highCD127low Трег (1), CD4+FoxP3+ Трег (2), Тх-акт (3), Тх17 (4), Тх1 (5), Тх2 (6)
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