Breast Cancer Research and Treatment

, Volume 162, Issue 1, pp 59–67 | Cite as

The incidence of cardiomyopathy in BRCA1 and BRCA2 mutation carriers after anthracycline-based adjuvant chemotherapy

  • Edward J. Pearson
  • Anju Nair
  • Yahya Daoud
  • Joanne L. Blum
Clinical trial



Breast cancer remains the fourth-leading cause of death in the United States. Nearly 10% of breast cancers are hereditary, with deleterious mutations in BRCA1 and BRCA2 genes being the leading cause. Anthracycline chemotherapy, used commonly for breast cancer, carries cardiotoxicity risk. Recent studies demonstrated anthracycline-induced cardiac failure in homozygous BRCA2-deficient mice and increased rates of heart failure in homozygous BRCA1-deficient mice following ischemic insult. Therefore, we conducted a retrospective matched cohort study to determine the rates of anthracycline-induced cardiomyopathy in breast cancer patients with germline mutation in BRCA1 or BRCA2 genes compared to age-matched patients without a BRCA1 or BRCA2 gene mutation.


The primary endpoint was to determine the rate of cardiomyopathy defined as either congestive heart failure or asymptomatic decline in ejection fraction to <50%. A total of 102 breast cancer patients who were BRCA gene mutation carriers (55 BRCA1, 45 BRCA2, and two with both), who received anthracycline-based chemotherapy were compared to a matched cohort of breast cancer patients with wild-type BRCA gene status.


We found a 4.9% rate of cardiomyopathy in the BRCA mutation carriers and 5.2% in the matched controls (p = 0.99). Cox proportional hazards model showed that only trastuzumab and hypertension were significantly associated with the development of cardiomyopathy in both groups (p < 0.05).


Given the limitations of a retrospective study, we saw no increased risk of cardiotoxicity among breast cancer patients with BRCA1 and/or BRCA2 gene mutations treated with standard doses of anthracycline compared to the general population.


BRCA1 BRCA2 Anthracycline Cardiotoxicity 



This study was supported, in part, by the Baylor University Medical Center, Charles A. Sammons Cancer Center Trainee Cancer Research Award.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

This study was approved by the Baylor Scott & White Institutional Review Board.


  1. 1.
    American Cancer Society. Cancer Facts & Figures 2016. Atlanta: American Cancer Society (2016)Google Scholar
  2. 2.
    The link between BRCA mutation and endothelial function. In: (2015 Feb 23)
  3. 3.
    Barac A, Lynce F, Smith KL, Mete M, Shara NM, Asch FM, Nardacci MP, Wray L, Herbolsheimer P, Nunes RA, Swain SM, Warren R, Peshkin BN, Isaacs C (2016) Cardiac function in BRCA1/2 mutation carriers with history of breast cancer treated with anthracyclines. Breast Cancer Res Treat 155:285–293CrossRefPubMedGoogle Scholar
  4. 4.
    Buzdar AU, Marcus C, Smith TL, Blumenschein GR (1985) Early and delayed clinical cardiotoxicity of doxorubicin. Cancer 55:2761–2765CrossRefPubMedGoogle Scholar
  5. 5.
    Campeau PM, Foulkes WD, Tischkowitz MD (2008) Hereditary breast cancer: new genetic developments, new therapeutic avenues. Hum Genet 124:31–42CrossRefPubMedGoogle Scholar
  6. 6.
    Chatterjee K, Zhang J, Honbo N, Karliner JS (2010) Doxorubicin cardiomyopathy. Cardiology 115:155–162CrossRefPubMedGoogle Scholar
  7. 7.
    Chen S, Parmigiani G (2007) Meta-analysis of BRCA1 and BRCA2 penetrance. J Clin Oncol 25:1329–1333CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Ewer MS, Ali MK, Mackay B, Wallace S, Valdivieso M, Legha SS, Benjamin RS, Haynie TP (1984) A comparison of cardiac biopsy grades and ejection fraction estimations in patients receiving Adriamycin. J Clin Oncol 2:112–117PubMedGoogle Scholar
  9. 9.
    Hartmann LC, Lindor NM (2016) The role of risk-reducing surgery in hereditary breast and ovarian cancer. N Engl J Med 374:454–468CrossRefPubMedGoogle Scholar
  10. 10.
    Hlatky MA, Boineau RE, Higginbotham MB, Lee KL, Mark DB, Califf RM, Cobb FR, Pryor DB (1989) A brief self-administered questionnaire to determine functional capacity (the duke activity status index). Am J Cardiol 64:651–654CrossRefPubMedGoogle Scholar
  11. 11.
    Ismail-Khan R, Sajjad M, Sun W, Soliman H, Han H, Minton S, Lancaster J, Pal T (2012) An exploratory study to determine if BRCA1 and BRCA2 mutation carriers have higher risk of cardiac toxicity. J Clin Oncol 30:1585Google Scholar
  12. 12.
    Jones AL, Barlow M, Barrett-Lee PJ, Canney PA, Gilmour IM, Robb SD, Plummer CJ, Wardley AM, Verrill MW (2009) Management of cardiac health in trastuzumab-treated patients with breast cancer: updated United Kingdom national cancer research institute recommendations for monitoring. Br J Cancer 100:684–692CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    L’Ecuyer T, Sanjeev S, Thomas R, Novak R, Das L, Campbell W, Heide RV (2006) DNA damage is an early event in doxorubicin-induced cardiac myocyte death. Am J Physiol Heart Circ Physiol 291:H1273–H1280CrossRefPubMedGoogle Scholar
  14. 14.
    Shukla PC, Singh KK, Quan A, Al-Omran M, Teoh H, Lovren F, Cao L, Rovira II, Pan Y, Brezden-Masley C, Yanagawa B, Gupta A, Deng CX, Coles JG, Leong-Poi H, Stanford WL, Parker TG, Schneider MD, Finkel T, Verma S (2011) BRCA1 is an essential regulator of heart function and survival following myocardial infarction. Nat Commun 2:593CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Singh KK, Shukla PC, Quan A, Desjardins JF, Lovren F, Pan Y, Garg V, Gosal S, Garg A, Szmitko PE, Schneider MD, Parker TG, Stanford WL, Leong-Poi H, Teoh H, Al-Omran M, Verma S (2012) BRCA2 protein deficiency exaggerates doxorubicin-induced cardiomyocyte apoptosis and cardiac failure. J Biol Chem 287:6604–6614CrossRefPubMedGoogle Scholar
  16. 16.
    Swain SM, Whaley FS, Ewer MS (2003) Congestive heart failure in patients treated with doxorubicin: a retrospective analysis of three trials. Cancer 97:2869–2879CrossRefPubMedGoogle Scholar
  17. 17.
    Thavendiranathan P, Poulin F, Lim KD, Plana JC, Woo A, Marwick TH (2014) Use of myocardial strain imaging by echocardiography for the early detection of cardiotoxicity in patients during and after cancer chemotherapy: a systematic review. J Am Coll Cardiol 63:2751–2768CrossRefPubMedGoogle Scholar
  18. 18.
    Von Hoff DD, Layard MW, Basa P, Davis HL Jr, Von Hoff AL, Rozencweig M, Muggia FM (1979) Risk factors for doxorubicin-induced congestive heart failure. Ann Intern Med 91:710–717CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  • Edward J. Pearson
    • 1
  • Anju Nair
    • 1
  • Yahya Daoud
    • 2
  • Joanne L. Blum
    • 1
  1. 1.Texas Oncology, Baylor Charles A. Sammons Cancer CenterBaylor University Medical CenterDallasUSA
  2. 2.Baylor Scott and White HealthDallasUSA

Personalised recommendations