Are we overlooking the effects of hypertension in breast cancer patients undergoing radiotherapy? The SAFE-FORWARD findings

The deleterious effects of radiotherapy on left and right ventricular function have been primarily described looking at the worsening of ejection fraction and strain.

Ultra-hypofractionated radiation therapy (RT), consisting of 5 treatment sessions following breast-conserving surgery, proved a non-inferior local control rates and a favorable toxicity profile. However, there is today no data on its effects on cardiac function.

SAFE-FORWARD was an observational prospective study that included patients with invasive breast cancer receiving whole breast irradiation at a dose of 26 Gy in 5 fractions. Patients were treated using tangential intensity-modulated radiation therapy fields with 6 or 10 MV beams. Each patient underwent clinical assessment and 3D-echocardiography before RT and at 2-, 6-, 12-, and 24-months post-treatment. A total of 50 women (median age 67 years, range 48-84 years) were enrolled in the study. Among them, 27 patients had left breast cancer (LBS) and 21 right breast cancer (RBS); two patients had bilateral breast cancer. Additionally, 33 patients received adjuvant endocrine therapy, and none was treated with adjuvant cardiotoxic drugs. The main cardiovascular risk factor identified was systemic arterial hypertension in 12 LBS and 11 RBS.

No significant changes were observed at the end of the follow-up period regarding the 3D left and 3D right ventricular ejection fraction (LVEF and RVEF), nor in left ventricular global strain (GLS) , although hypertensive patients started with a lower GLS (-19.9±2.0 vs -21.0±2.0, p=0.018) (Figure 1).

In hypertensive LBS patients, there were significant changes in the diastolic function parameters. The mitral E/A ratio decreased after 6 months, E/e’ increased after 12 months, and the left atrial volume index (LAVI) was higher at the baseline and showed a further increase. Left atrial strain (LAS) exhibited a reduction in reservoir values (LASr) starting at 6 months, while LAS conduit (LAScd) and LAS contraction terminal (LASct) decreased after 12 months (Figure 2). Blood pressure measurements did not differ between hypertensive and normotensive LBS patients (mean values during the 2 years were 129±13/76±7 in normotensive and 133±17/77±8 in hypertensive LBS patients).

The two-year follow-up of this prospective observational study indicated that ultra-hypofractionated RT consisting of five fractions did not significantly affect the 3D LVEF, GLS, or 3D RVEF. However, in the cohort of hypertensive patients undergoing LBS RT a more sensitive measure of LAS showed a decline in reservoir function and in both conduit and terminal contraction. Notably, the systemic arterial pressure values in this cohort was not significantly higher than those in the normotensive group, and both groups had values in the high-normal range. This observation seems to warrant a more rigorous blood pressure control in breast cancer patients undergoing LBS RT.Figure 1  Figure 2