A comparison of cardiovascular and pulmonary morbidities and risk factors in breast cancer survivors compared to an age-matched female control group in the Lifelines prospective population cohort.

PURPOSE: To provide more insight into late treatment-related toxicities among breast cancer (BC) survivors by comparing morbidities and risk factors between BC survivors and age-matched controls. MATERIALS AND METHODS: All female participants diagnosed with BC before inclusion in Lifelines, a population-based cohort in the Netherlands, were selected and matched 1:4 to female controls without any oncological history on birth year. Baseline was defined as the age at BC diagnosis. Outcomes were obtained from questionnaires and functional analyses performed at entry to Lifelines (follow-up 1; FU1) and several years later (FU2). Cardiovascular and pulmonary events were defined as morbidities that were absent at baseline but present at FU1 or FU2. RESULTS: The study consisted of 1,325 BC survivors and 5,300 controls. The median period from baseline (i.e., BC treatment) to FU1 and FU2 was 7 and 10 years, respectively. Among BC survivors more events of heart failure (OR: 1.72 [1.10-2.68]) and less events of hypertension (OR: 0.79 [0.66-0.94]) were observed. At FU2, more electrocardiographic abnormalities were found among BC survivors compared to controls (4.1% vs. 2.7%, respectively; p = 0.027) and Framingham scores for the 10-year risk of coronary heart disease were lower (difference: 0.37%; 95% CI [-0.70 to -0.03%]). At FU2, BC survivors had more frequently a forced vital capacity below the lower limit of normal than controls (5.4% vs. 2.9%, respectively; p = 0.040). CONCLUSION: BC survivors are at risk of late treatment-related toxicities despite a more favourable cardiovascular risk profile compared to age-matched female controls.

Supraventricular cardiac conduction system exposure in breast cancer patients treated with radiotherapy and association with heart and cardiac chambers doses.

Purpose: To assess sinoatrial node (SAN) and atrioventricular node (AVN) doses for breast cancer (BC) patients treated with 3D-CRT and evaluate whether "large" cardiac structures (whole heart and four cardiac chambers) would be relevant surrogates. Material and methods: This single center study was based on 116 BCE patients (56 left-sided, 60 right-sided) treated with 3D-CRT without respiratory gating strategies and few IMN irradiations from 2009 to 2013. The heart, the left and right ventricles (LV, RV), the left and right atria (LA, RA) were contoured using multi-atlases for auto-segmentation. The SAN and the AVN were manually delineated using a specific atlas. Based on regression analysis, the coefficients of determination (R2) were estimated to evaluate whether "large" cardiac structures were relevant surrogates (R2 > 0.70) of SAN and AVN doses. Results: For left-sided BC, mean doses were: 3.60 ± 2.28 Gy for heart, 0.47 ± 0.24 Gy for SAN and 0.74 ± 0.29 Gy for AVN. For right-sided BC, mean heart dose was 0.60 ± 0.25 Gy, mean SAN dose was 1.57 ± 0.63 Gy (>85 % of patients with SAN doses > 1 Gy) and mean AVN dose was 0.51 ± 0.14 Gy. Among all "large" cardiac structures, RA appeared as the best surrogate for SAN doses (R2 > 0.80). Regarding AVN doses, the RA may also be an interesting surrogate for left-sided BC (R2 = 0.78), but none of "large" cardiac structures appeared as relevant surrogates among right-sided BC (all R2 < 0.70), except the LA for patients with IMN (R2 = 0.83). Conclusions: In BC patients treated 10 years ago with 3D-CRT, SAN and AVN exposure was moderate but could exceed 1 Gy to the SAN in many right-sided patients with no IMN-inclusion. The RA appeared as an interesting surrogate for SAN exposure. Specific conduction nodes delineation remains necessary by using modern radiotherapy techniques.

Light-chain paraproteins with lupus anticoagulant activity.

A patient with newly diagnosed multiple myeloma manifested by urine kappa light-chain excretion and a small monoclonal spike (0.4 g/dl), presented with lower extremity deep venous thrombosis. A preheparin plasma-activated partial thromboplastin time (aPTT) was prolonged at 68 sec (normal control 26-42 sec). Additional studies confirmed the presence of lupus anticoagulant activity in the serum: the modified Russell Viper Venom Time (MRVVT) was 73 sec (normal control 24-42 sec) and with a 50:50 mix of the patient's plasma and pooled normal plasma, the MRVVT remained prolonged. Kappa light chains (LC) were isolated from the patient's urine and their purity confirmed by electrophoresis and immunofixation using specific immunoglobulin antisera. The patient's LC mixed with pooled normal plasma demonstrated LA activity by in vitro clotting tests (plasma-activated partial thromboplastin time 62 sec, with normal control of 45 sec), MRVVT of 44 sec with normal control of 35 sec. Purified urinary kappa light chains from a control patient with multiple myeloma and normal clotting studies, failed to prolong either the plasma-activated partial thromboplastin time or the MRVVT. We hypothesize that kappa LC in our patient demonstrated LA activity, which was unique to these LCs. Paraproteins with LA activity, to date, have included only intact immunoglobulins (Ig). While intact Ig paraproteins have been reported to possess LA activity, this is the first report to our knowledge of light-chain paraproteins possessing similar activity and resulting in clinically evident thrombosis. Light chain paraproteins could serve as useful models for further study of the mechanisms of activity of acquired LA inhibitors.