Cardioprotective Effect of β-Adrenoceptor Blockade in Patients With Breast Cancer Undergoing Chemotherapy

Abstract

Background-Chemotherapy with trastuzumab and anthracycline is associated with incident heart failure (HF) in patients with breast cancer. We hypothesized that continuous incidental use of β-blocker agents (BB) was protective against HF in patients without established structural heart disease who were receiving trastuzumab and anthracycline. Methods and Results-We identified 920 consecutive patients with breast cancer (age 52.3±11.0 years) with normal ejection fraction before receiving trastuzumab and anthracycline therapy at our institution between 2005 and 2010. Using a propensity score and a greedy 5 to 1 digit-matching algorithm, 106 of these patients on continuous BB during cancer treatment were matched with 212 patients from the same pool with similar characteristics but not on continuous BB. During a median follow-up of 3.2±2.0 years, 32 incident HF admissions were identified in these 318 patients with breast cancer, whereas 28 cancer-related (noncardiac) deaths occurred before any incident HF. Cumulative incidence regression models and cause-specific hazards of new HF events were estimated from competing risk Cox models of time-dependent covariates. Although trastuzumab therapy showed significant association with incident HF, independent of anthracycline-related cardiotoxicity (hazard ratio, 9.0; 95% confidence interval, 3.0-27.0; P<0.0001), continuous use of BB was associated with lower risk of new HF events (hazard ratio, 0.2; 95% confidence interval, 0.1-0.5; P=0.003). Conclusions-Coincidental, continuous use of BB is associated with lower incidence of HF in patients with breast cancer and normal baseline ejection fraction in a competing risk framework, and after matching for demographics, clinical, and cancer-related treatment characteristics. Prospective randomized clinical trials to validate these findings are warranted. (Circ Heart Fail. 2013;6:420-426.)

Expert Consensus for Multimodality Imaging Evaluation of Adult Patients during and after Cancer Therapy: A Report from the American Society of Echocardiography and the European Association of Cardiovascular Imaging

“…192,193 The use of vasoactive medications may be limited by the risk for side effects (especially dizziness and hypotension) 194 and is supported by limited evidence for angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, and b-blockers. [195][196][197][198][199] Given the frequency of asymptomatic LV dysfunction and the potential side effects associated with the proposed regimens, early identification and treatment may be the optimal path. Treatment of sub-clinical LV dysfunction is based on a strategy of early detection of myocardial disease with either biomarkers or imaging.…”

2016 ESC Position Paper on cancer treatments and cardiovascular toxicity developed under the auspices of the ESC Committee for Practice Guidelines

“…U pacjentów z chorobą przerzutową, u których rozwinęła się HF, zaobserwowano związek między leczeniem inhibitorami ACE i beta-adrenolitykami a poprawą LVEF po 12 miesiącach, a kolejne podanie trastuzumabu niekoniecznie prowadziło do ponownego wystąpienia HF [282]. Ponadto stwierdzono, że u chorych na raka piersi, z prawidłową LVEF przed leczeniem trastuzumabem i antracykliną, przewlekłe podawanie beta-adrenolityków zmniejsza częstość występo-wania HF [37,38].…”

Cardiotoxicity From Human Epidermal Growth Factor Receptor‐2 (HER2) Targeted Therapies

“…Observational studies and small randomized clinical trials suggest a benefit in early initiation of angiotensin‐converting enzyme inhibitors and beta‐blockers for the prevention of cardiotoxicity 15, 89, 90, 91, 92, 93. The PRADA (Prevention of Cardiac Dysfunction During Adjuvant Breast Cancer Therapy) trial tested whether angiotensin receptor blockers and/or beta‐blockers would be effective in preventing cardiotoxicity in patients diagnosed with breast cancer receiving anthracycline‐based chemotherapy with and without trastuzumab.…”