Less Trastuzumab Cardiotoxicity in Beta-Blocker Users



ORLANDO – Beta-blockers appear to be cardioprotective in breast cancer patients on trastuzumab, according to a prospective case-control study.

The risk of developing new-onset heart failure or left ventricular dysfunction during 1 year on trastuzumab (Herceptin) was 65% lower in 30 breast cancer patients who were incidentally on a beta-blocker at the start of the monoclonal antibody therapy than in 167 other breast cancer patients who were not, Thomas B. Cook, Ph.D., reported at the annual scientific sessions of the American Heart Association.

The women on a beta-blocker averaged 59 years of age, a full 8 years older than the breast cancer patients not on a beta-blocker. The patients on a beta-blocker also had significantly higher rates of hypertension, diabetes, obesity, and smoking. After adjustment for these traditional cardiovascular risk factors as well as other factors predisposing to heart failure, including prior treatment with anthracyclines or radiation therapy, the beta-blocker group had an adjusted 83% lower risk of developing cardiotoxicity during 1 year of follow-up on trastuzumab (P = .006).

This is a small hypothesis-generating study. The findings warrant a proper randomized controlled trial assessing the impact of prophylactic beta-blocker therapy in breast cancer patients going on trastuzumab, Dr. Cook asserted.

In all, 22 of the 197 breast cancer patients were on an ACE inhibitor at the time they started on trastuzumab. Logistic regression analysis indicated no cardioprotective effect for this class of medication, according to Dr. Cook of the Cleveland Clinic Foundation.

New-onset heart failure was diagnosed in 11% of patients not on a beta-blocker and in none who were. Left ventricular dysfunction – defined as an echocardiographically documented ejection fraction decline of at least 10% – occurred in 40% of trastuzumab users not on a beta-blocker, compared to 20% who were.

A trajectory analysis of serial echocardiographic exams revealed overall significant declines in left ventricular ejection fraction in patients during their year of follow-up on trastuzumab; however, the decline was markedly steeper in those who were not on a beta-blocker.

Interestingly, neither prior treatment with anthracyclines, even in excess of four cycles, nor other prior chemotherapy were predictive of cardiotoxicity in this series of trastuzumab-treated women. Current smoking, however, was associated with a 4.2-fold increased risk.

Dr. Cook reported no financial conflicts.

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