Accepted Manuscript

In reply to letter entitled “Heart failure and breast cancer: emerging controversiesregarding some cardioprotective strategies”

Ronald M. Witteles, MD Akanksha Thakur, MD

PII: S1071-9164(14)00175-4

DOI: 10.1016/j.cardfail.2014.04.015

Reference: YJCAF 3291

To appear in: Journal of Cardiac Failure

Received Date: 10 April 2014

Accepted Date: 10 April 2014

Please cite this article as: Witteles RM, Thakur A, In reply to letter entitled “Heart failure and breastcancer: emerging controversies regarding some cardioprotective strategies”, Journal of Cardiac Failure(2014), doi: 10.1016/j.cardfail.2014.04.015.

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In reply to letter entitled “Heart failure and breast cancer: emerging controversies regarding some

cardioprotective strategies”

Ronald M. Witteles MD1 and Akanksha Thakur MD

2

1 Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, CA

2 Department of Medicine, Stanford University School of Medicine, Stanford, CA

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We thank Dr. Patane for his thoughtful comments, and for specifically addressing the question of the

effects of cardiac medications on cancer outcomes. This issue has drawn significant attention in recent

years, spurred largely by the suggestion of improved cancer outcomes with the (usually coincidental)

concomitant use of beta-blockers and, to a lesser extent, inhibitors of the renin-angiotensin-aldosterone

system (RAAS).[1-6] As Dr. Patane accurately notes, a series of subsequent publications have drawn

disparate conclusions, ranging from no effect on cancer outcomes to improved outcomes to worsened

outcomes.

We certainly agree with the call for further – and preferably lager – studies addressing this issue.

However, our primary opinion and message is that given that use of beta-blockers and RAAS-inhibitors

has been well validated in patients with left ventricular dysfunction in general and in cancer therapy-

associated cardiac toxicity in particular [7-10], this should be the standard of care unless there is a clear

and consistent signal of harm from a cancer standpoint. If anything, the preponderance of the evidence

to date favors improved cancer outcomes, particularly for beta-blockers.

Disclosures: None

References

1. Chae YK, Valsecchi ME, Kim J, et al. Reduced risk of breast cancer recurrence in patients using

ACE inhibitors, ARBs, and/or statins. Cancer Invest. 2011;29:585-93.

2. Barron TI, Connolly RM, Sharp L, Bennett K, Visvanathan K. Beta blockers and breast cancer

mortality: a population-based study. J Clin Oncol. 2011;29:2635-44.

3. Powe DG, Voss MJ, Zanker KS, et al. Beta-blocker drug therapy reduces secondary cancer

formation in breast cancer and improves cancer specific survival. Oncotarget. 2010;1:628-38.

4. Melhem-Bertrandt A, Chavez-Macgregor M, Lei X et al. Beta-blocker use is associated with

improved relapse-free survival in patients with triple-negative breast cancer. J Clin Oncol.

2011;29:2645-52.

5. Chae YK, Brown EN, Lei X, et al. Use of ACE inhibitors and angiotensin receptor blockers and

primary breast cancer outcomes. J Cancer. 2013;4:549-56.

6. Powe DG, Entschladen F. Targeted therapies: Using beta-blockers to inhibit breast cancer

progression. Nat Rev Clin Oncol. 2011;8:511-2.

7. Hunt SA, Abraham WT, Chin MH, et al. 2009 focused update incorporated into the ACC/AHA

2005 guidelines for the diagnosis and management of heart failure in adults. Circulation.

2009;119:e391-479.

8. Bosch X, Rovira M, Sitges M, et al. Enalapril and carvedilol for preventing chemotherapy-induced

left ventricular systolic dysfunction in patients with malignant hemopathies. J Am Coll Cardiol.

2013;61:2355-62.

9. Cardinale D, Colombo A, Sandri MT, et al. Prevention of high-dose chemotherapy-induced

cardiotoxicity in high-risk patients by angiotensin converting enzyme inhibition. Circulation.

206;114:2474-81.

10. Kalay N, Basar E, Ozdogru I, et al. Protective effects of carvedilol against anthracycline-induced

cardiomyopathy. J Am Coll Cardiol. 2006;48:2258-62.