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Cardiovascular Risk in Breast Cancer Patients Receiving Estrogen or Progesterone Antagonists

  • Cardio-oncology (M Fradley, Section Editor)
  • Published:
Current Treatment Options in Cardiovascular Medicine Aims and scope Submit manuscript

Abstract

Purpose of review

The purpose of this review is to summarize the current literature on estrogen and progesterone antagonists and their effects on the cardiovascular system.

Recent findings

Estrogen and progesterone antagonists reduce cancer-related recurrence and mortality in women with ER-positive breast cancer. Recent studies, however, suggest that women with early stage breast cancer are more likely to die of cardiovascular disease than recurrent breast cancer. Estrogen antagonists have been shown to reduce endothelial function, to increase lipid profiles and to alter body composition accelerating atherosclerotic changes.

Summary

While clinical trial data demonstrates mixed results of the impact of estrogen antagonists on cardiovascular risk, there is a growing body of evidence that estrogen suppression and estrogen antagonists result in biologic effects on the endothelium, altering lipid profiles and accelerating the risk of atherosclerosis. Further longitudinal work however is needed.

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References and Recommended Reading

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2017. CA Cancer J Clin. 2017;67(1):7–30.

    Article  PubMed  Google Scholar 

  2. Meyer MR, Barton M. Estrogens and coronary artery disease: new clinical perspectives. Adv Pharmacol. 2016;77:307–60.

    Article  PubMed  CAS  Google Scholar 

  3. Gradishar WJ, Anderson BO, Balassanian R, Blair SL, Burstein HJ, Cyr A, et al. NCCN guidelines insights: breast cancer, version 1.2017. Journal of the National Comprehensive Cancer Network: JNCCN. 2017;15(4):433–51.

    Article  PubMed  Google Scholar 

  4. Cuzick J, Sestak I, Baum M, Buzdar A, Howell A, Dowsett M, et al. Effect of anastrozole and tamoxifen as adjuvant treatment for early-stage breast cancer: 10-year analysis of the ATAC trial. The lancet oncology. 2010;11(12):1135–41.

    Article  PubMed  CAS  Google Scholar 

  5. Regan MM, Neven P, Giobbie-Hurder A, Goldhirsch A, Ejlertsen B, Mauriac L, et al. Assessment of letrozole and tamoxifen alone and in sequence for postmenopausal women with steroid hormone receptor-positive breast cancer: the BIG 1-98 randomised clinical trial at 8.1 years median follow-up. The lancet oncology. 2011;12(12):1101–8.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  6. Coombes RC, Kilburn LS, Snowdon CF, Paridaens R, Coleman RE, Jones SE, et al. Survival and safety of exemestane versus tamoxifen after 2–3 years’ tamoxifen treatment (Intergroup Exemestane Study): a randomised controlled trial. Lancet. 2007;369(9561):559–70.

    Article  PubMed  CAS  Google Scholar 

  7. Pan H, Gray RG, Davies C, Peto R, Bergh J, Pritchard KI, et al. Predictors of recurrence during years 5–14 in 46,138 women with ER+ breast cancer allocated 5 years only of endocrine therapy (ET). J Clin Oncol. 2016;34 (suppl; abstr 505).

  8. Pan H, Gray R, Braybrooke J, Davies C, Taylor C, McGale P, et al. 20-year risks of breast-cancer recurrence after stopping endocrine therapy at 5 years. N Engl J Med. 2017;377(19):1836–46.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Davies C, Pan H, Godwin J, Gray R, Arriagada R, Raina V, et al. Long-term effects of continuing adjuvant tamoxifen to 10 years versus stopping at 5 years after diagnosis of oestrogen receptor-positive breast cancer: ATLAS, a randomised trial. Lancet. 2013;381(9869):805–16.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  10. Goss PE, Ingle JN, Pritchard KI, Robert NJ, Muss H, Gralow J, et al. Extending aromatase-inhibitor adjuvant therapy to 10 years. N Engl J Med. 2016;375(3):209–19.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  11. • Armenian SH, Xu L, Ky B, Sun C, Farol LT, Pal SK, et al. Cardiovascular disease among survivors of adult-onset cancer: a community-based retrospective cohort study. J Clin Oncol. 2016;34(10):1122–30. Outlines elevated CV risk in breast cancer survivors

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  12. Bradshaw PT, Stevens J, Khankari N, Teitelbaum SL, Neugut AI, Gammon MD. Cardiovascular disease mortality among breast cancer survivors. Epidemiology. 2016;27(1):6–13.

    Article  PubMed  PubMed Central  Google Scholar 

  13. •• Blaes A, Beckwith H, Florea N, Hebbel R, Solovey A, Potter D, et al. Vascular function in breast cancer survivors on aromatase inhibitors: a pilot study. Breast Cancer Res Treat. 2017. Endothelial function and the use of aromatase inhibitors in breast cancer survivors.

  14. Mendelsohn ME, Karas RH. The protective effects of estrogen on the cardiovascular system. N Engl J Med. 1999;340(23):1801–11.

    Article  PubMed  CAS  Google Scholar 

  15. Wassertheil-Smoller S, Hendrix SL, Limacher M, Heiss G, Kooperberg C, Baird A, et al. Effect of estrogen plus progestin on stroke in postmenopausal women: the Women's Health Initiative: a randomized trial. JAMA. 2003;289(20):2673–84.

    Article  PubMed  CAS  Google Scholar 

  16. Rivera CM, Grossardt BR, Rhodes DJ, Brown RD Jr, Roger VL, Melton LJ III, et al. Increased cardiovascular mortality after early bilateral oophorectomy. Menopause. 2009;16(1):15–23.

    Article  PubMed  PubMed Central  Google Scholar 

  17. • Rocca WA, Gazzuola-Rocca L, Smith CY, Grossardt BR, Faubion SS, Shuster LT, et al. Accelerated accumulation of multimorbidity after bilateral oophorectomy: a population-based cohort study. Mayo Clin Proc. 2016;91(11):1577–89. Increased cardiovascular risk in those undergoing oophorectomy

    Article  PubMed  Google Scholar 

  18. Hodis HN, Mack WJ, Henderson VW, Shoupe D, Budoff MJ, Hwang-Levine J, et al. Vascular effects of early versus late postmenopausal treatment with estradiol. N Engl J Med. 2016;374(13):1221–31.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  19. Gradishar WJ, Anderson BO, Balassanian R, Blair SL, Burstein HJ, Cyr A, et al. NCCN guidelines insights: breast cancer, version 1.2017. J Natl Compr Cancer Netw. 2017;15(4):433–51.

    Article  Google Scholar 

  20. Hutchins LF, Unger JM, Crowley JJ, Coltman CA Jr, Albain KS. Underrepresentation of patients 65 years of age or older in cancer-treatment trials. N Engl J Med. 1999;341(27):2061–7.

    Article  PubMed  CAS  Google Scholar 

  21. Dunn BK, Ford LG. Breast cancer prevention: results of the National Surgical Adjuvant Breast and Bowel Project (NSABP) breast cancer prevention trial (NSABP P-1: BCPT). Eur J Cancer. 2000;36(Suppl 4):S49–50.

    Article  PubMed  Google Scholar 

  22. Howell A, Cuzick J, Baum M, Buzdar A, Dowsett M, Forbes JF, et al. Results of the ATAC (Arimidex, Tamoxifen, Alone or in Combination) trial after completion of 5 years’ adjuvant treatment for breast cancer. Lancet. 2005;365(9453):60–2.

    Article  PubMed  CAS  Google Scholar 

  23. Mouridsen HT. The differences in outcome between ATAC and BIG 1-98 suggest efficacy differences between these two nonsteroidal AIs. Cancer Investig. 2010;28(Suppl 1):1–3.

    Article  Google Scholar 

  24. Coates AS, Keshaviah A, Thurlimann B, Mouridsen H, Mauriac L, Forbes JF, et al. Five years of letrozole compared with tamoxifen as initial adjuvant therapy for postmenopausal women with endocrine-responsive early breast cancer: update of study BIG 1-98. J Clin Oncol: Off J Am Soc Clin Oncol. 2007;25(5):486–92.

    Article  CAS  Google Scholar 

  25. Khosrow-Khavar F, Filion KB, Al-Qurashi S, Torabi N, Bouganim N, Suissa S, et al. Cardiotoxicity of aromatase inhibitors and tamoxifen in postmenopausal women with breast cancer: a systematic review and meta-analysis of randomized controlled trials. Ann Oncol: Off J Eur Soc Med Oncol. 2017;28(3):487–96.

    CAS  Google Scholar 

  26. Chapman JA, Shepherd LE, Ingle JN, Muss HB, Pritchard KI, Gelmon KA, et al. Competing risks of death in women treated with adjuvant aromatase inhibitors for early breast cancer on NCIC CTG MA.27. Breast Cancer Res Treat. 2016;156(2):343–9.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  27. Abdel-Qadir H, Amir E, Fischer HD, Fu L, Austin PC, Harvey PJ, et al. The risk of myocardial infarction with aromatase inhibitors relative to tamoxifen in post-menopausal women with early stage breast cancer. European journal of cancer (Oxford, England: 1990). 2016;68:11–21.

    Article  CAS  Google Scholar 

  28. Matthews AKS, Lyon AR, Smeeth L, Bhaskaran K. Assessing the association between hormone therapy use in female breast cancer and subsequent risk of cardiovascular disease: a cohort study in the UK Clinical Practice Research Datalink. London, UK: Global Cardio-oncology Society meeting; 2017.

  29. Rubinshtein R, Kuvin JT, Soffler M, Lennon RJ, Lavi S, Nelson RE, et al. Assessment of endothelial function by non-invasive peripheral arterial tonometry predicts late cardiovascular adverse events. Eur Heart J. 2010;31(9):1142–8.

    Article  PubMed  Google Scholar 

  30. Luca MC, Liuni A, Harvey P, Mak S, Parker JD. Effects of estradiol on measurements of conduit artery endothelial function after ischemia and reperfusion in premenopausal women. Can J Physiol Pharmacol. 2016;94(12):1304–8.

    Article  PubMed  CAS  Google Scholar 

  31. Lew R, Komesaroff P, Williams M, Dawood T, Sudhir K. Endogenous estrogens influence endothelial function in young men. Circ Res. 2003;93(11):1127–33.

    Article  PubMed  CAS  Google Scholar 

  32. Gnant M, Steger GG, Bartsch R. Pathological complete remission and long-term outcome-what do we know in 2016? Lancet Oncol. 2016;17(6):693–4.

    Article  PubMed  Google Scholar 

  33. Feldman RD. Aldosterone and blood pressure regulation: recent milestones on the long and winding road from electrocortin to KCNJ5, GPER, and beyond. Hypertension. 2014;63(1):19–21.

    Article  PubMed  CAS  Google Scholar 

  34. de Haas EC, Zwart N, Meijer C, Suurmeijer AJ, Meijer K, Guchelaar HJ, et al. Association of PAI-1 gene polymorphism with survival and chemotherapy-related vascular toxicity in testicular cancer. Cancer. 2010.

  35. Haas E, Bhattacharya I, Brailoiu E, Damjanovic M, Brailoiu GC, Gao X, et al. Regulatory role of G protein-coupled estrogen receptor for vascular function and obesity. Circ Res. 2009;104(3):288–91.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  36. Diano S, Horvath TL, Mor G, Register T, Adams M, Harada N, et al. Aromatase and estrogen receptor immunoreactivity in the coronary arteries of monkeys and human subjects. Menopause (New York, NY). 1999;6(1):21–8.

    Article  CAS  Google Scholar 

  37. Blaes A, Prizment A, Koene RJ, Konety S. Cardio-oncology related to heart failure: common risk factors between cancer and cardiovascular disease. Heart Fail Clin. 2017;13(2):367–80.

    Article  PubMed  PubMed Central  Google Scholar 

  38. Koene RJ, Prizment AE, Blaes A, Konety SH. Shared risk factors in cardiovascular disease and Cancer. Circulation. 2016;133(11):1104–14.

    Article  PubMed  PubMed Central  Google Scholar 

  39. Mast ME, Heijenbrok MW, Petoukhova AL, Scholten AN, Schreur JH, Struikmans H. Preradiotherapy calcium scores of the coronary arteries in a cohort of women with early-stage breast cancer: a comparison with a cohort of healthy women. Int J Radiat Oncol Biol Phys. 2012;83(3):853–8.

    Article  PubMed  CAS  Google Scholar 

  40. Davis MK, Rajala JL, Tyldesley S, Pickles T, Virani SA. The prevalence of cardiac risk factors in men with localized prostate cancer undergoing androgen deprivation therapy in British Columbia. Canada J Oncol. 2015;2015:820403.

    PubMed  Google Scholar 

  41. •• Fuster JJ, MacLauchlan S, Zuriaga MA, Polackal MN, Ostriker AC, Chakraborty R, et al. Clonal hematopoiesis associated with TET2 deficiency accelerates atherosclerosis development in mice. Science. 2017;355(6327):842–7. Describes the possible underlying mechanism linking cancer and cardiovascular risk

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  42. Jaiswal S, Natarajan P, Silver AJ, Gibson CJ, Bick AG, Shvartz E, et al. Clonal hematopoiesis and risk of atherosclerotic cardiovascular disease. N Engl J Med. 2017;377(2):111–21.

    Article  PubMed  PubMed Central  Google Scholar 

  43. van Londen GJ, Perera S, Vujevich K, Rastogi P, Lembersky B, Brufsky A, et al. The impact of an aromatase inhibitor on body composition and gonadal hormone levels in women with breast cancer. Breast Cancer Res Treat. 2011;125(2):441–6.

    Article  PubMed  CAS  Google Scholar 

  44. Hom EK, Duprez DA, Jacobs DR Jr, Bluemke DA, Brumback LC, Polak JF, et al. Comparing arterial function parameters for the prediction of coronary heart disease events: the multi-ethnic study of atherosclerosis (MESA). Am J Epidemiol. 2016;184(12):894–901.

    Article  PubMed  PubMed Central  Google Scholar 

  45. Simon MS, Beebe-Dimmer JL, Hastert TA, Manson JE, Cespedes Feliciano EM, Neuhouser ML, et al. Cardiometabolic risk factors and survival after breast cancer in the Women’s Health Initiative. Cancer. 2018.

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Authors and Affiliations

  1. University of Minnesota, 424 Delaware Street, S.E., MMC 480, Minneapolis, MN, 55455, USA

    Anne H. Blaes MD, MS & Daniel A. Duprez MD, PhD

  2. University of Pittsburgh, Pittsburgh, PA, USA

    G. J. van Londen MD, MS

  3. Mayo Clinic, Rochester, MN, USA

    Nicole Sandhu MD, PhD & Amir Lerman MD

Authors
  1. Anne H. Blaes MD, MS
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  2. G. J. van Londen MD, MS
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  3. Nicole Sandhu MD, PhD
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  4. Amir Lerman MD
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  5. Daniel A. Duprez MD, PhD
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Corresponding author

Correspondence to Anne H. Blaes MD, MS.

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Conflict of Interest

Anne H. Blaes reports research support (K12-HD055887).

G. J. van Londen, Nicole Sandhu, Amir Lerman, and Daniel A. Duprez declare that they have no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

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This article is part of the Topical Collection on Cardio-oncology

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Blaes, A.H., van Londen, G.J., Sandhu, N. et al. Cardiovascular Risk in Breast Cancer Patients Receiving Estrogen or Progesterone Antagonists. Curr Treat Options Cardio Med 20, 48 (2018). https://doi.org/10.1007/s11936-018-0637-8

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  • DOI: https://doi.org/10.1007/s11936-018-0637-8

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