Markers of Cardiotoxicity in Early Breast Cancer Patients Treated With a Hypofractionated Schedule: A Prospective Study.

PURPOSE: To evaluate, in a series of early breast cancer (BC) patients treated with hypofractionated adjuvant radiotherapy (RT), whether N-terminal-pro hormone B-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin I assay measurements can predict acute clinical or preclinical cardiotoxicity. PATIENTS AND METHODS: The study comprised 44 consecutive patients, who underwent conservative surgery with or without (neo)adjuvant chemotherapy and hypofractionated adjuvant RT. The RT schedule consisted in a total dose of 42.4 Gy in 16 fractions administered 5 days per week. Twenty-one patients received a subsequent boost to the tumor bed consisting of a total dose of 10 Gy in 4 fractions delivered via a direct electron field. All patients underwent 12-lead electrocardiogram, echocardiogram, and cardiac clinical examinations before RT to assess cardiovascular risk factors; these examinations were repeated yearly for 5 consecutive years. High-sensitivity cardiac troponin I and NT-proBNP were analyzed from serum samples at baseline, after delivery of the fourth and 16th RT fractions, and 12 months after treatment completion. RESULTS: No increase in cardiac troponin I and B-type natriuretic peptide levels related to left breast irradiation was observed. No statistical difference in NT-proBNP and high-sensitivity troponin I levels between left- and right-sided BC was found. An increase was observed of B-type natriuretic peptide levels at baseline, during treatment, and until 12 months after RT related to hypertension, with the P value near to the .05 threshold for age and chemotherapy. CONCLUSION: Conformational hypofractionated RT in left-sided BC may not cause acute myocardial damage. Early cardiac screening may be used to identify patients with cardiologic risk factors, patients who are older than 60 years, and patients who received chemotherapy that could result in clinically relevant cardiac pathologies.

Brain natriuretic peptide as a cardiac marker of transient radiotherapy-related damage in left-sided breast cancer patients: A prospective study.

PURPOSE: Our study evaluated brain natriuretic peptide (BNP) changes over time after adjuvant radiotherapy (RT) in women with left-sided breast cancer investigating its correlation with heart dosimetric parameters. METHODS: Forty-three patients underwent clinical cardiac examination, electrocardiogram (ECG), echocardiography and BNP measurement before RT (T0) and 1 (T1), 6 (T6) and 12 months (T12) after. After T12 cardiac assessment was performed annually in each patient. Mean values and standard deviation (SD) of BNP, left ventricular ejection fraction (LVEF), V20, V25, V30, V45 and mean dose were calculated. Normalized BNP (BNPn) was calculated as follows: BNPnT1 = BNPT1/BNPT0, BNPnT6 = BNPT6/BNPT0, BNPnT12 = BNPT12/BNPT0. Absolute BNP and BNPn values were used for data analysis. RESULTS: Median follow-up from the end of RT to the last check-up was 87 months (range 37-120 months). Minimum follow-up was 74 months except for two patients, who died at respectively 37 and 47 months after RT. In all patients LVEF did not change significantly (p = 0.22) after RT. BNP increased significantly (p < 0.001), particularly 1 and 6 months after RT. It slightly decreased after 12 months. BNP did not correlate with V20, V25, V30, V45, mean dose and MHD. All BNPn correlated significantly (p < 0.05) with V20, V25, V30, V45, mean dose and MHD. Four patients had a cardiac event; in the only subject who developed myocardial infarction, V20, V25, V30 and V45 were the highest and BNP increased from T1 and persisted high even at T12. CONCLUSION: Our results confirm that BNP could be a useful minimally invasive marker of early RT related cardiac impairment.

Kinetics of B-type natriuretic peptide plasma levels in patients with left-sided breast cancer treated with radiation therapy: Results after one-year follow-up.

PURPOSE: To analyze temporal changes of B-type natriuretic peptide (BNP) used as index of heart remodeling in left-sided breast cancer patients after radiotherapy (RT) and its relationship with dosimetric parameters. METHODS AND MATERIALS: BNP and dose-volume parameters for heart and ventricle were collected in 59 patients (median age 58.0 years) during a 1-year follow-up. Biochemical measurements were performed before the RT treatment (T0), at 15 days during RT (T(15day)), at the end of RT (T(endRT)), and then at 1, 3, 6, 9, 12 months (T1, T3, T6, T9 and T12). A logistical regression analysis was performed to identify demographic characteristics, dosimetric variables and risk factors associated with increased values of BNP. RESULTS: The ratio between the BNP value at T12 and the BNP value at T0 (BNP(T12)/BNP(T0)) increased significantly (p < 0.01). A significant association was found between the variation of BNP values after 1 year and the isodose received by 50% of the volume (D50% [Gy]) both to the heart (p = 0.03) and ventricle (p = 0.04). CONCLUSIONS: BNP plasma levels could provide additional information about subclinical RT-induced cardiotoxicity earlier than traditional ecocardiographic data.