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

Purpose
Breast cancer (BC) survivors are at increased risk of late treatment-related toxicities. This study aimed to evaluate whether incidences of cardiac- and pulmonary morbidities after BC treatment were increased by comparing BC survivors to an age-matched female control group without oncological history.
Materials and Methods
The LifeLines population-based cohort follows 167,729 participants from the northern part of the Netherlands over a 30-years period and enables cross-sectional, longitudinal and observational research. For the current study, all female LifeLines participants diagnosed with BC before inclusion in LifeLines were selected and randomly matched to females without any oncological history with an identical age (ratio of 1:4). Cardiovascular and pulmonary endpoints were obtained from questionnaires and measurements, such as anthropometric analysis, blood pressure, blood serum analysis, electrocardiograms (ECG) and spirometry. Differences in LifeLines measurements, performed at entry to LifeLines (follow-up 1; FU1) and five years later (FU2), were evaluated between both groups. Incidences of cardiovascular and pulmonary morbidities, defined as morbidities that were absent at baseline (i.e., before BC treatment) but present at FU1 or FU2, were compared between both groups. 
Results
The study consisted of 1,325 BC survivors and 5,300 controls. FU1 and FU2 were performed after a median period from the reconstructed baseline of 7 and 10 years, respectively. More incidences of heart failure (OR: 1.72 [1.10 – 2.68]) and less incidences of hypertension were observed (OR: 0.79 [0.66 – 0.94]) among BC survivors compared to controls. At FU2, BC survivors compared to controls had more abnormal ECGs (4.1% vs. 2.7%, respectively; p=0.027) and lower Framingham scores for the 10-year risk of coronary heart disease at FU2 (difference: 0.37%; 95% CI [-0.70 - -0.03%]). At FU2, forced vital capacities were more frequently below the lower limit of normal among BC survivors compared to 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