Changes in vascular function during breast cancer treatment

AimsBreast cancer (BC) survivors are at increased risk of cardiovascular disease. We evaluated whether chemotherapy induces early or late vascular dysfunction in vivo. MethodsEarly-stage BC patients (n= 33) underwent measurements of forearm blood flow (FBF), 24-hour blood pressure (BP), aortic pulse wave velocity and inflammatory markers before (T0), 14days after (T1) and 12months after (T2) chemotherapy. FBF was assessed during intra-arterial infusion of acetylcholine (ACh), ACh during simultaneous nitric oxide synthase inhibition with L-NG-monomethyl arginine, and during infusion of sodium nitroprusside. Controls matched by age and menopausal status were examined for baseline comparison. ResultsAt T0, absolute FBF in the BC patients did not differ from controls. At T1, ACh-induced absolute FBF was higher compared to T0. ACh-induced FBF decreased significantly at T2, evaluated as area under the dose-response curve, and when corrected for FBF in the contralateral arm (FBF ratio at T0: 4.05, 95% confidence interval [2.54; 5.74] and T2: 2.77 [2.41; 3.50]), without difference evident during L-NG-monomethyl arginine infusion. FBF during sodium nitroprusside infusion remained unchanged. Pulse wave velocity and BP remained unchanged. Asymmetric dimethylarginine (T0: 0.68 mu mol/L0.17, T1: 0.75 mu mol/L +/- 0.16) and the inflammation-related biomarkers Cd163 (T0: 1.86mg/L [1.68; 2.05], T1: 2.04mg/L [1.76; 2.4]) and Cd206 (T0: 0.22mg/L [0.19; 0.26], T1: 0.27mg/L [0.23; 0.30]) all increased significantly at T1, but returned to baseline values at T2. L-arginine was significantly increased at both T1 (78.5 mu mol/L [68.9; 86.6]) and T2 (76.8 mu mol/L [66.9; 90.6]), compared to T0 (59.6 mu mol/L [53.7; 68.0]). ConclusionChemotherapy for BC seems associated with early amplification of endothelium-dependent vasodilation and inflammation. One year after chemotherapy, microvascular dysfunction persists in terms of reduced NO-dependent vasodilation without alterations in BP or arterial stiffness.