Cardiovascular safety of modern radiotherapy techniques in breast cancer

Radiotherapy (RT) plays a key role in breast cancer treatment, improving overall survival and reducing recurrence. There have been concerns about RT-related cardiovascular (CV) complications from older techniques used in the latter half of the 20th century. Modern RT methods such as intensity-modulated radiotherapy (IMRT) and three-dimensional conformal radiotherapy (3D-CRT) allow for reduced cardiac doses and may mitigate long-term CV risk.

This study aimed to evaluate the incidence of CV events among contemporary breast cancer patients treated with modern RT techniques and to examine dose–response parameters for predicting CV outcomes.

Patients with breast cancer from the multicentre CARDIOTOX registry (2012–2017) were analyzed. The primary endpoint was a composite of CV death, ischemic events, cancer therapy related cardiovascular dysfunction (CTRCD), arrhythmias, and valvular disease. Multivariable Cox models and Fine–Gray competing risk analyses for non-CV death were performed to compare RT-exposed and unexposed groups, with a subanalysis by tumor laterality. The associations between mean cardiac dose, V25 and V30 (volume of the heart receiving at least 25Gy and 30 Gy, respectively), and the primary endpoint were also assessed.

A total of 756 patients (99% women; mean age 54 years) were included in the analysis, with a median follow-up of 4.15 years. 543 patients (71.8%) received RT, and 213 were unexposed. Baseline CV risk was low in both groups, although the RT group received more chemotherapy and hormonal therapy and underwent more breast-conserving surgery. Radiation doses were also low, with a median heart dose mean of 2.4 Gy. Overall, there were 23 events in the RT group and 9 in the non-RT group (Figure 1). In adjusted competing risk models, RT was not associated with a significantly increased CV risk (subdistribution hazard ratio 0.63, 95% CI 0.26–1.56; p=0.32), with no differences between left- and right-sided RT. No significant interactions with anthracyclines or anti-HER2 therapies were found. High risk criteria (HR) based on mean heart dose showed poor performance in predicting CV events, while V25 and specially V30 provided better risk stratification (Figure 2).

In this contemporary cohort of breast cancer patients with low baseline CV risk, modern RT techniques were not linked to an increased incidence of CV events. Dose–volume histogram parameters such as V25 and V30 may offer superior prognostic value compared to mean heart dose.Fig 1.

CV primary event incidence