Aims and methods
The incidence and outcome of HER2-related cardiotoxicity is not well described in the routine care of patients with advanced HER2 positive breast cancer. We reviewed BioGrid’s© “Treatment of Advanced Breast Cancer In The HER2 Positive Australian Patient” registry data to elucidate this problem further.
162 female patients from seven Australian centers with a median age of 58.5 years (range 27-95) were included. 69 women (43%) had no risk factors for cardiotoxicity; 12 (18%) had ≥2 risk factors. Median baseline left ventricular ejection fraction (LVEF) was 64% (range 50-77).
Of the 149 women who received HER2-targeted therapy, 8 (6%) experienced cardiotoxicity (of any CTCAE left ventricular systolic dysfunction grade) in the first-line setting; 5 of which were asymptomatic. The median age (61 years) and baseline LVEF (60%, range 54-61) were similar to the whole cohort. However, only 2/8 (25%) patients had no risk factors for cardiotoxicity, whilst 3/8 (38%) had ≥2 risk factors. The onset of cardiotoxicity occurred at a median of 9 months (range 3.5-16.8) of treatment. In 7/8 patients, HER2 therapy was withheld. Resolution of cardiotoxicity was seen in 5/8 patients (median time to recovery 2.8 months (range 1.4-3.8). There was no difference between cardiotoxicity grade and resolution. Of the 7 patients that had treatment withheld, only one resumed therapy. No patients died secondary to cardiotoxicity.
The incidence of cardiotoxicity in our dataset is low compared to other retrospective reviews. While there may be under-reporting, the results provide reassurance for clinicians, particularly when ≥2 risk factors are present, that HER2-targeted therapy can be safely administered and that where cardiotoxicity develops, it usually resolves with treatment discontinuation. The safety and ongoing management following re-challenge remains uncertain and requires investigation. Further research is required to understand optimal patient selection for HER2 targeted therapy, cardiac monitoring, and cardiotoxicity management.