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Cardiotoxicities of Non-Chemotherapeutic Metastatic Breast Cancer Treatments

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Abstract

Purpose of Review

Although mortality rates have declined significantly in recent years, breast cancer remains the second most common cause of cancer death in women, with rates significantly higher among women with metastatic disease. New therapeutic agents have improved the prognosis of patients with metastatic breast cancer but raise concerns around the risk of cardiovascular disease. This review aims to discuss the oncologic treatment of the different subtypes of breast cancer along with the cardiac complications associated with each therapy.

Recent Findings

This article emphasizes human epidermal growth factor receptor targeted therapies with a focus on incidence of cardiotoxicity, reversibility, long-term outcomes, and management in high-risk patients. This review will address the use of cardiac biomarkers to monitor for toxicity, as well as the utility of cardiac imaging, including global longitudinal strain as a prognostic factor. We will also include recent findings on tyrosine kinase inhibitors, cyclin dependent kinase 4/6, and immune checkpoint inhibitors.

Summary

Cardiotoxicity may lead to premature discontinuation of novel cancer therapies; optimizing cardiovascular risk factors and close monitoring for cardiotoxicity allow patients to maximize their oncologic and cardiovascular outcomes.

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References

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

  1. American Cancer Society’s publications, Cancer Facts & Figures 2022. Available at https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/annual-cancer-facts-and-figures/2022/2022-cancer-facts-and-figures.pdf. Accessed 2 Dec 2022.

  2. U.S. Cancer Statistics Working Group. U.S. Cancer Statistics Data Visualizations Tool, based on 2021 submission data (1999-2019): U.S. Department of Health and Human Services, Centers for Disease Control and Prevention and National Cancer Institute; https://www.cdc.gov/cancer/dataviz, released in November 2022.

  3. American Cancer Society’s publications, Breast Cancer Facts & Figures 2022-2024. Available at https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/breast-cancer-facts-and-figures/2022-2024-breast-cancer-fact-figures-acs.pdf. Accessed 2 Dec 2022.

  4. Ross JS, Slodkowska EA, Symmans WF, Pusztai L, Ravdin PM, Hortobagyi GN. The HER-2 receptor and breast cancer: ten years of targeted anti-HER-2 therapy and personalized medicine. Oncologist. 2009;14(4):320–68.

    Article  CAS  PubMed  Google Scholar 

  5. Giordano SH, Franzoi MAB, Temin S, Anders CK, Chandarlapaty S, Crews JR, Kirshner JJ, Krop IE, Lin NU, Morikawa A, Patt DA, Perlmutter J, Ramakrishna N, Davidson NE. Systemic therapy for advanced human epidermal growth factor receptor 2–positive breast cancer: ASCO guideline update. J Clin Oncol. 2022;40(23):2612–35. ASCO most recent guideline regarding oncologic treatment of HER2-positive breast cancer.

    Article  CAS  PubMed  Google Scholar 

  6. Lyon AR & al, 2022 ESC Guidelines on cardio-oncology developed in collaboration with the European Hematology Association (EHA), the European Society for Therapeutic Radiology and Oncology (ESTRO) and the International Cardio-Oncology Society (IC-OS): developed by the task force on cardio-oncology of the European Society of Cardiology (ESC). Eur Heart J. 2022; 41(43): 4229-4361. Updated and most recent cardio-oncology guideline addressing the cardiac management of known cardiotoxic drugs as well as newer oncologic treatments associated with cardiac side effects.

  7. Nemeth BT, Varga ZV, Wu WJ, Pacher P. Trastuzumab cardiotoxicity: from clinical trial to experimental studies. Br J Pharmacol. 2017;174(21):3727–48.

    Article  CAS  PubMed  Google Scholar 

  8. Varricchi G, Ameri P, Cadeddu C, Ghigo A, Madonna R, Marone G, Mercurio V, Monte I, Novo G, Parrella P, Pirozzi F, Pecoraro A, Spallarossa P, Zito C, Mercuro G, Pagliaro P, Tocchetti CG. Antineoplastic drug-induced cardiotoxicity: a redox perpective. Front Physiol. 2018;167(9):1–18.

    Google Scholar 

  9. Slamon DJ, Leyland-Jones B, Shak S, Fuchs H, Paton V, Bajamonde A, Fleming T, Eiermann W, Wolter J, Pegram M, Baselga J, Norton L. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpress HER2. N Engl J Med. 2001;344:783–92. Trial in HER2-positive metastatic breast cancer assessing the efficacy of trastuzumab in combination with chemotherapy and demonstrating improved progression-free survival and overall survival compared to chemotherapy alone. Unexpectedly, this trial revealed an increased risk of heart failure associated with trastuzumab.

    Article  CAS  PubMed  Google Scholar 

  10. Mantarro S, Rossi M, Bonifazi M, D’Amico R, Blandizzi C, La Vecchia C, Negri E, Moja L. Risk of severe cardiotoxicity following treatment with trastuzumab: a meta-analysis of randomized and cohort studies of 29,000 women with breast cancer. Intern Emerg Med. 2016;11:123–40.

    Article  PubMed  Google Scholar 

  11. De Azambuja E, Procter MJ, van Veldhuisen DJ, Agbor-Tarh D, Metzger-Filho O, Steinseifer J, Untch M, Smith IE, Gianni L, Baselga J, Jackisch C, Cameron DA, Bell R, Leyland-Jones B, Dowsett M, Gelber RD, Piccart-Gebhart MJ, Suter TM. Trastuzumab-associated cardiac events at 8 years of median follow-up in the herceptin adjuvant trial (BIG 1-01). J Clin Oncol. 2014;32(20):2159–65.

    Article  PubMed  Google Scholar 

  12. Chen J, Long JB, Hurria A, Owusu C, Steingart RM, Gross CP. Incidence of heart failure or cardiomyopathy after adjuvant trastuzumab therapy for breast cancer. J Am Coll Cardiol. 2012;60(24):2504–12.

    Article  CAS  PubMed  Google Scholar 

  13. Yu AF, Flynn JR, Moskowitz CS, Scott JM, Oeffinger KC, Dang CT, Liu JE, Jones LW, Steingart RM. Long-term cardiopulmonary consequences of treatment-induced cardiotoxicity in survivors of ERBB2-positive breast cancer. JAMA Cardiol. 2020;5(3):309–17.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Capelan M, Pugliano L, De Azambuja E, Bozovic I, Saini KS, Sotiriou C, Loi S, Piccart-Gebhart MJ. Pertuzumab: new hope for patients with HER2-positive breast cancer. Ann Oncol. 2013;24(2):272–82.

    Article  Google Scholar 

  15. Swain SM, Miles D, Kim S-B, Im Y-H, Semiglazov V, Ciruelos E, Schneeweiss A, Loi S, Monturus E, Clark E, Knott A, Restuccia E, Benyunes MC, Cortés J. Pertuzumab, trastuzumab, and docetaxel for HER2-positive metastatic breast cancer (CLEOPATRA): end-of-study results from a double-blind, randomised, placebo-controlled, phase 3 study. Lancet Oncol. 2020;21(4):519–30.

    Article  CAS  PubMed  Google Scholar 

  16. Swain SM, Ewer MS, Cortés J, Amadori D, Miles D, Knott A, Clark E, Benyunes MC, Ross G, Baselga J. Cardiac tolerability of pertuzumab plus trastuzumab plus docetaxel in patients with HER2-positive metastatic breast cancer in CLEOPATRA: a randomized, double-blind, placebo-controlled phase III study. Oncologist. 2013;18(3):257–64.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Chen S, Liang Y, Feng Z, Wang M. Efficacy and safety of HER2 inhibitor in combination with or without pertuzumab for HER2-positive breast cancer: a systematic review and meta-analysis. BMC Cancer. 2019;19:973.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Rugo HS, Im S-A, Cardoso F, Cortés J, Curigliano G, Musolino A, Pegram MD, Wright GS, Saura C, Escrivá-de-Romaní S, De Laurentiis M, Levy C, Brown-Glaberman U, Ferrero J-M, de Boer M, Kim S-B, Petráková K, Yardley DA, Freedman O, et al. Efficacy of margetuximab vs trastuzumab in patients with pretreated ERBB2-positive advanced breast cancer: a phase 3 randomized clinical trial. JAMA Oncol. 2021;7(4):573–84.

    Article  PubMed  Google Scholar 

  19. U.S. Food and Drug Administration. Kadcyla® highlights of prescribing information. Available at https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/125427lbl.pdf. Accessed 2 Feb 2023.

  20. Pondé N, Ameye L, Lambertini M, Paesmans M, Piccart M, de Azambuja E. Trastuzumab emtansine (T-DM1)-associated cardiotoxicity: pooled analysis in advanced HER2-positive breast cancer. Eur J Cancer. 2020;126:65–73.

    Article  PubMed  Google Scholar 

  21. Modi S, Jacot W, Yamashita T, Sohn J, Vidal M, Tokunaga E, Tsurutani J, Ueno NT, Prat A, Chae YS, Lee KS, Niikura N, Park YH, Xu B, Wang X, Gil-Gil M, Li W, Pierga J-Y, Im S-A, et al. Trastuzumab deruxtecan in previously treated HER2-low advanced breast cancer. N Engl J Med. 2022;387:9–20.

    Article  CAS  PubMed  Google Scholar 

  22. Wolff AC, Hale Hammond ME, Allison KH, Harvey BE, Mangu PB, Bartlett J, Bilous M, Ellis IO, Fitzgibbons P, Hanna W, Jenkins RB, Press MF, Spears PA, Vance GH, Viale G, McShane LM, Dowsett M. Human epidermal growth factor receptor 2 testing in breast cancer: American Society of Clinical Oncology/College of American Pathologists Clinical Practice Guideline Focused Update. J Clin Oncol. 2018;36(20):2105–22.

    Article  CAS  PubMed  Google Scholar 

  23. Blackwell KL, Burstein HJ, Storniolo AM, Rugo H, Sledge G, Koehler M, Ellis C, Casey M, Vukelja S, Bischoff J, Baselga J, O’Shaughnessy J. Randomized study of lapatinib alone or in combination with trastuzumab in women with ErbB2-positive, trastuzumab-refractory metastatic breast cancer. J Clin Oncol. 2010;28(7):1124–30.

    Article  CAS  PubMed  Google Scholar 

  24. Choi HD, Chang MJ. Cardiac toxicities of lapatinib in patients with breast cancer and other HER2-positive cancers: a meta-analysis. Breast Cancer Res Treat. 2017;166:927–36.

    Article  CAS  PubMed  Google Scholar 

  25. U.S. Food and Drug Administration. Tykerb® highlights of prescribing information. Available at https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/022059s007lbl.pdf. Accessed 2 Dec 2022.

  26. Murthy RK, Loi S, Okines A, Paplomata E, Hamilton E, Hurvitz SA, Lin NU, Borges V, Abramson V, Anders C, Bedard PL, Oliveira M, Jakobsen E, Bachelot T, Shachar SS, Müller V, Braga S, Duhoux FP, Greil R, et al. Tucatinib, trastuzumab, and capecitabine for HER2-positive metastatic breast cancer. N Engl J Med. 2020;382:597–609.

    Article  CAS  PubMed  Google Scholar 

  27. Chan A, Moy B, Mansi J, Ejlertsen B, Holmes FA, Chia S, Iwata H, Gnant M, Loibl S, Barrios CH, Somali I, Smichkoska S, Martinez N, Garcia Alonso M, Link JS, Mayer IA, Cold S, Morales Murillo S, Senecal F, et al. Final efficacy results of neratinib in HER2-positive hormone receptor-positive early-stage breast cancer from the phase III ExteNET trial. Clin Breast Cancer. 2021;21(1):80–91.e7.

    Article  CAS  PubMed  Google Scholar 

  28. Saura C, Oliveira M, Feng Y-H, Dai M-S, Chen S-W, Hurvitz SA, Kim S-B, Moy B, Delaloge S, Gradishar W, Masuda N, Palacova M, Trudeau ME, Mattson J, Sim Yap Y, Hou M-F, De Laurentiis M, Yeh Y-M, Chang H-T, et al. Neratinib plus capecitabine versus lapatinib plus capecitabine in HER2-positive metastatic breast cancer previously treated with ≥ 2 HER2-directed regimens: phase III NALA trial. J Clin Oncol. 2020;38(27):3138–49.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Waliany S, Caswell-Jin J, Riaz F, Myall N, Zhu H, Witteles RM, Neal JW. Pharmacovigilance analysis of heart failure associated with anti-HER2 monotherapies and combination regimens for cancer. J Am Coll Cardiol CardioOncol. 2023;

  30. Lambert J, Lamacie M, Thampinathan B, Altaha M, Esmaeilzadeh M, Nolan M, Urzua Fresno C, Somerset E, Amir E, Marwick TH, Wintersperger BJ, Thavendiranathan P. Variability in echocardiography and MRI for detection of cancer therapy cardiotoxicity. Heart. 2020;106(11):817–23.

    Article  CAS  PubMed  Google Scholar 

  31. Plana JC, Galderisi M, Barac A, Ewer MS, Ky B, Scherrer-Crosbie M, Ganame J, Sebag IA, Agler DA, Badano LP, Banchs J, Cardinale D, Carver J, Cerqueira M, DeCara JM, Edvardsen T, Flamm SD, Force T, Lancellotti P. 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. J Am Soc Echocardiogr. 2014;27(9):911–39.

    Article  PubMed  Google Scholar 

  32. Korkmaz-Icöz S, Szczesny B, Marcatti M, Li S, Ruppert M, Lasitschka F, Loganathan S, Szabó C, Szabó G. Olaparib protects cardiomyocytes against oxidative stress and improves graft contractility during early phase after heart transplantation in rats. Br J Pharmacol. 2017;175(2):246–61.

    Article  PubMed  PubMed Central  Google Scholar 

  33. Virani SA, Dent S, Brezden-Masley C, Clarke B, Davis MK, Jassal DS, Johnson C, Lemieux J, Paterson I, Sebag IA, Simmons C, Sulpher J, Thain K, Thavendiranathan P, Wentzell JR, Wurtele N, Côté MA, Fine NM, Haddad H, et al. Canadian Cardiovascular Society guidelines for evaluation and management of cardiovascular complication of cancer therapy. Can J Cardiol. 2016;32(7):831–84.

    Article  PubMed  Google Scholar 

  34. Armenian SH, Lacchetti C, Barac A, Carver J, Constine LS, Denduluri N, Dent S, Douglas PS, Durand J-B, Ewer M, Fabian C, Hudson M, Jessup M, Jones LW, Ky B, Mayer EL, Moslehi J, Oeffinger K, Ray K, et al. Prevention and monitoring of cardiac dysfunction in survivors of adult cancers: American Society of Clinical Oncology Clinical Practice Guideline. J Clin Oncol. 2017;35(8):893–911.

    Article  PubMed  Google Scholar 

  35. Negishi K, Negishi T, Harc JL, Haluska BA, Plana JC, Marwick T. Independent and incremental value of deformation indices for prediction of trastuzumab-induced cardiotoxicity. J Am Soc Echocardiogr. 2013;26(5):493–8.

    Article  PubMed  Google Scholar 

  36. Sawaya H, Sebag IA, Plana JC, Januzzi JL, Ky B, Cohen V, Gosavi S, Carver JR, Wiegers SE, Martin RP, Picard MH, Gerszten RE, Halpern EF, Passeri J, Kuter I, Scherrer-Crosbie M. Early detection and prediction of cardiotoxicity in chemotherapy-treated patients. Am J Cardiol. 2011;107(9):1375–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Mignot A, Donal E, Zaroui A, Reant P, Salem A, Hamon C, Monzy S, Roudaut R, Habib G, Lafitte S. Global longitudinal strain as a major predictor of cardiac events in patients with depressed left ventricular function: a multicenter study. J Am Soc Echocardiogr. 2010;23(10):1019–24.

    Article  PubMed  Google Scholar 

  38. Kalam K, Otahal P, Marwick TH. Prognostic implication of global LV dysfunction: a systematic review and meta-analysis of global longitudinal strain and ejection fraction. Heart. 2014;100(21)

  39. Cardinale D, Colombo A, Lamantia G, Colombo N, Civelli M, De Giacomi G, Rubino M, Veglia F, Fiorentini C, Cipolla CM. Anthracycline-induced cardiomyopathy. J Am Coll Cardiol. 2010;55(3):213–20.

    Article  CAS  PubMed  Google Scholar 

  40. Thavendiranathan P, Negishi T, Somerset E, Negishi K, Penicka M, Lemieux J, Aakhus S, Miyazaki S, Shirazi M, Galderisi M, Marwick TH. Strain-guided management of potentially cardiotoxic cancer therapy. J Am Coll Cardiol. 2021;77(4):392–401.

    Article  CAS  PubMed  Google Scholar 

  41. U.S. Food and Drug Administration. Herceptin® highlights of prescribing information. Available at https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/103792s5250lbl.pdf. Accessed 2 Dec 2022.The FDA recommendations for LVEF monitoring with the use of trastuzumab are based on early trastuzumab trials. Guidelines and subsequent FDA labelling for other HER-2 targeted therapies are based on the initial FDA directive established for trastuzumab.

  42. U.S. Food and Drug Administration. Perjeta® highlights of prescribing information. Available at https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/125409s051lbl.pdfAccessed 2 Dec 2022.

  43. U.S. Food and Drug Administration. Margenza® highlights of prescribing information. Available at https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/761150s000lbl.pdfAccessed 2 Dec 2022.

  44. U.S. Food and Drug Administration. Enhertu® highlights of prescribing information. Available at https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/761139s011lbl.pdfAccessed 2 Feb 2023.

  45. Zardavas D, Suter TM, Van Veldhuisen DJ, Steinseifer J, Noe J, Lauer S, Al-Sakaff N, Piccart-Gebhart MJ, de Azambuja E. Role of troponins I and T and N-terminal prohormone of brain natriuretic peptide in monitoring cardiac safety of patients with early-stage human epidermal growth factor receptor 2–positive breast cancer receiving trastuzumab: a herceptin adjuvant study cardiac marker substudy. J Clin Oncol. 2016;35:878–84.

    Article  PubMed  Google Scholar 

  46. Ponde N, Bradbury I, Lambertini M, Ewer M, Campbell C, Ameels H, Zardavas D, Di Cosimo S, Baselga J, Huober J, Izquierdo M, Fumagalli D, Bozovic-Spasojevic I, Maetens M, Harbeck N, Pusztai L, Berghorn M, Im Y-H, Ruiz Borrego M, et al. Cardiac biomarkers for early detection and prediction of trastuzumab and/or lapatinib-induced cardiotoxicity in patients with HER2-positive early-stage breast cancer: a NeoALTTO sub-study (BIG 1-06). Breast Cancer Res Treat. 2018;168:631–8.

    Article  CAS  PubMed  Google Scholar 

  47. Blancas I, Martín-Pérez FJ, Garrido JM, Rodríguez-Serrano F. NT-proBNP as predictor factor of cardiotoxicity during trastuzumab treatment in breast cancer patients. Breast. 2020;54:106–13.

    Article  PubMed  PubMed Central  Google Scholar 

  48. Demissei BG, Hubbard RA, Zhang L, Smith AM, Sheline K, McDonald C, Narayan V, Domchek SM, DiMichele A, Shah P, Clark AS, Fox K, Matro J, Bradbury AR, Knollman H, Getz KD, Armenian SH, Januzzi JL, Wilson Tang WH, et al. Changes in cardiovascular biomarkers with breast cancer therapy and associations with cardiac dysfunction. J Am Heart Assoc. 2020;9(2):e014708.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Bouwer NI, Liesting C, Kofflard MJM, Sprangers-van Campen SM, Brugts JJ, Kitzen JJ, Fouraux MA, Levin M-D, Boersma E. NT-proBNP correlates with LVEF decline in HER2-positive breast cancer patients treated with trastuzumab. Cardio-Oncology. 2019;5:4.

    Article  PubMed  PubMed Central  Google Scholar 

  50. Nowsheen S, Aziz K, Park JY, Lerman A, Villarraga HR, Ruddy KJ, Herrmann J. Trastuzumab in female breast cancer patients with reduced left ventricular ejection fraction. J Am Heart Assoc. 2018;7(15)

  51. Lynce F, Barac A, Geng X, Dang C, Yu AF, Smith KL, Gallagher C, Pohlmann PR, Nunes R, Herbolsheimer P, Warren R, Srichai MB, Hofmeyer M, Cunningham A, Timothee P, Asch FM, Shajahan-Haq A, Tan MT, Isaacs C, Swain SM. Prospective evaluation of the cardiac safety of HER2-targeted therapies in patients with HER2-positive breast cancer and compromised heart function: the SAFE-HEaRt study. Breast Cancer Res Treat. 2019;175(3):595–603.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Khoury K, Lynce F, Barac A, Geng X, Dang C, Fu AF, Smith KL, Gallagher C, Pohlmann PR, Nunes R, Herbolsheimer P, Warren R, Srichai MB, Hofmeyer M, Asch F, Tan M, Isaacs C, Swain SM. Long-term follow-up assessment of cardiac safety in SAFE-HEaRt, a clinical trial evaluating the use of HER2-targeted therapies in patients with breast cancer and compromised heart function. Breast Cancer Res Treat. 2021;185(3):863–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Leong DP, Cosman T, Alhussein MM, Kumar Tyagi N, Karampatos S, Barron CC, Wright D, Tandon V, Magloire P, Joseph P, Conen D, Devereaux PJ, Ellis PM, Mukherjee SD, Dhesy-Thind S. Safety of continuing trastuzumab despite mild cardiotoxicity: a phase I trial. J Am Coll Cardio Onc. 2019;1(1):1–10.

    Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  55. Khosrow-Khavar F, Filion KB, Bouganim N, Suissa S, Azoulay L. Aromatase inhibitors and the risk of cardiovascular outcomes in women with breast cancer. Circulation. 2020;141(7):549–59.

    Article  PubMed  Google Scholar 

  56. Abdulrahman Alomar S, Gaman A, Prabahar K, Ahnaf Arafah O, Almarshood F, Baradwan S, Abdullah Saud Aboudi S, Abuzaid M, Almubarki A, Alomar O, Al-Badawi IA, Salem H, Abu-Zaid A. The effect of tamoxifen on the lipid profile in women: a systematic review and meta-analysis of randomized controlled trials. Exp Gerontol. 2022;159

  57. Early Breast Cancer Trialists’ Collaborative Groupe (EBCTCG). Relevance of breast-cancer hormone receptors and other factors to the efficacy of adjuvant tamoxifen: patient-level meta-analysis of randomized trial. Lancet. 2011;378(9793):7710784.

    Article  Google Scholar 

  58. Reis SE, Costantino JP, Wickerham DL, Tan-Chiu E, Wang J, Kavanah M, National Surgical Adjuvant Breast and Bowel Project Breast Cancer Prevention Trial Investigators. Cardiovascular effects of tamoxifen in women with and without heart disease: breast cancer prevention trial. J Natl Cancer Inst. 2001;93(1):16–21.

    Article  CAS  PubMed  Google Scholar 

  59. Pollack IF, DaRosso RC, Robertson PL, Jakacki RL, Mirro JR Jr, Blatt J, Nicholson S, Packer RJ, Allen JC, Cisneros A, Jordan VC. A phase I study of high-dose tamoxifen for the treatment of refractory malignant gliomas of childhood. Clin Cancer Res. 1997;3(7):1109–15.

    CAS  PubMed  Google Scholar 

  60. Cuzick J, Forbes J, Edwards R, Baum M, Cawthorn S, Coates A, Hamed A, Howell A, Powles T. First results from the International Breast Cancer Intervention Study (IBIS-I): a randomized prevention trial. Lancet. 2002;360(9336):817–24.

    Article  CAS  PubMed  Google Scholar 

  61. Baselga J, Campone M, Piccart M, Burris HA III, Rugo HS, Sahmoud T, Noguchi S, Gnant M, Pritchard KI, Lebrun F, Beck JT, Ito Y, Yardley D, Deleu I, Perez A, Bachelot T, Vittori L, Xy Z, Mukhopadhyay P, et al. Everolimus in postmenopausal hormone-receptor-positive advanced breast cancer. N Engl J Med. 2012;366:520–9.

    Article  CAS  PubMed  Google Scholar 

  62. Karvelas G, Roumpi A, Komporozos C, Syrigos K. Everolimus as cancer therapy: cardiotoxic or an unexpected antiatherogenic agent? A narrative review. Hell J Cardiol. 2018;59(4):196–200.

    Article  Google Scholar 

  63. Combs Scott S, Lee SS, Abraham J. Mechanisms of therapeutic CDK4/6 inhibition in breast cancer. Semin Oncol. 2017;44(6):385–94.

    Article  Google Scholar 

  64. Giuliano M, Schettini F, Rognoni C, Milani M, Jerusalem G, Bachelot T, De Laurentiis M, Thomas G, De Placido P, Arpino G, De Placido S, Cristofanilli M, Giordano A, Puglisi F, Pistilli B, Prat A, Del Mastro L, Venturini S, Generali D. Endocrine treatment versus chemotherapy in postmenopausal women with hormone receptor-positive, HER2-negative, metastatic breast cancer: a systematic review and network meta-analysis. Lancet Oncol. 2019;20(10):1360–9.

    Article  CAS  PubMed  Google Scholar 

  65. West MT, Smith CE, Kaempf A, Kohs TCL, Amirsoltani R, Ribkoff J, Lee Choung J, Palumbo A, Mitri Z, Shatzel JJ. CDK 4/6 inhibitors are associated with a high incidence of thrombotic events in women with breast cancer in real-world practice. Eur J Haematol. 2021;106(5):634–42.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Fradley MG, Nguyen N, Chen Y, Guha A, Upshaw JN, Ky B, Gong Y. Abstract 16720: cardiovascular toxicities of cyclin dependent kinase (cdk) 4/6 inhibitors in metastatic breast cancer patients. Circulation. 2020;142(3)

  67. Mollon LE, Anderson E, Dean JL, Warholak TL, Aizer A, Platt EA, Tang DH, Davis LE. A systematic litterature review of the prognostic and predictive value of PIK3CA mutations in HR+/HER2- metastatic breast cancer. Clin Breast Cancer. 2020;20(3):e232–43.

    Article  CAS  PubMed  Google Scholar 

  68. Yang T, Meoli DF, Moslehi J, Roden DM. Inhibition of the α-subunit of phosphoinositide 3-kinase in heart increases late sodium current and is arrhythmogenic. J Pharmacol Exp Ther. 2018;365(3):460–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Cardoso F, Paluch-Schimon S, Senkus E, Curigliano G, Aapro MS, André F, Barrios CH, Bergh J, Bhattacharyya GS, Biganzoli L, Boyle F, Cardoso M-J, Carey LA, Cortés J, El Saghir NS, Elzayat M, Eniu A, Fallowfield L, Francis PA, et al. 5th ESO-ESMO international consensus guidelines for advanced breast cancer (ABC 5). Ann Oncol. 2020;31(12):1623–49.

    Article  CAS  PubMed  Google Scholar 

  70. Granier C, De Guillebon E, Blanc C, Roussel H, Badoual C, Colin E, Saldmann A, Gey A, Oudard S, Tartour E. Mechanisms of action and rationale for the use of checkpoint inhibitors in cancer. ESMO Open. 2017;2(2):e000213.

    Article  PubMed  PubMed Central  Google Scholar 

  71. Cortes J, Cescon DW, Rugo HS, Nowecki Z, Im S-A, Yusof M, al. Pembrolizumab plus chemotherapy versus placebo plus chemotherapy for previously untreated locally recurrent inoperable or metastatic triple-negative breast cancer (KEYNOTE-355): a randomised, placebo-controlled, double-blind, phase 3 clinical trial. Lancet. 2020;396(10265):1817–28.

    Article  PubMed  Google Scholar 

  72. Li C, Bhatti SA, Ying J. Immune checkpoint inhibitors-associated cardiomyopathy. Cancers. 2022;14(5):1145.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Mahmood SS, Fradley MG, Cohen JV, Nohria A, Reynolds KL, Heinzerling LM, Sullivan RJ, Damrongwatanasuk R, Chen CL, Gupta D, Kirchberger MC, Awadalla M, Hassan MZO, Moslehi JJ, Shah SP, Ganatra S, Thavendiranathan P, Lawrence DP, Groarke JD, Neilan TG. Myocarditis in patients treated with immune checkpoint inhibitors. J Am Coll Cardiol. 2018;71(16):1755–64.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Drobni ZD, Alvi RM, Taron J, Zafar A, Murphy SP, Rambarat PK, Mosaria RC, Lee C, Zlotoff DA, Raghu VK, Hartmann SE, Gilman HK, Gong J, Zubiri L, Sullivan RJ, Reynolds KL, Mayrhofer T, Zhang L, Hoffmann U, Neilan TG. Association between immune checkpoint inhibitors with cardiovascular events and atherosclerotic plaque. Circulation. 2020;142(24):2299–311.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Curigliano G, Lenihan D, Fradley M, Ganatra S, Barac A, Blaes A, Herrmann J, Porter C, Lyon AR, Lancellotti P, Patel A, DeCara J, Mitchell J, Harrison E, Moslehi J, Witteles R, Calabro MG, Orecchia R, de Azambuja E, et al. Management of cardiac disease in cancer patients throughout oncological treatment: ESMO consensus recommendations. Ann Oncol. 2020;31(2):171–90.

    Article  CAS  PubMed  Google Scholar 

  76. Awadalla M, Mahmood SS, Groarke JD, Hassan MZO, Nohria A, Rokicki A, Murphy SP, Mercaldo ND, Zhang L, Zlotoff DA, Reynolds KL, Alvi RM, Banerji D, Liu S, Heinzerling L, Jones-O’ Connor M, Bakar RB, Cohen JV, Kirchberger MC, et al. Global longitudinal strain and cardiac events in patients with immune checkpoint inhibitor-related myocarditis. J Am Coll Cardiol. 2020;75(5):467–78.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Zhang L, Awadalla M, Mahmood SS, Nohria A, Hassan MZO, Thuny F, Zlotoff DA, Murphy SP, Stone JR, Golden DLA, Alvi RM, Rokicki A, Jones-O’ Connor M, Cohen JV, Heinzerling LM, Mulligan C, Armanious M, Barac A, Forrestal BJ, et al. Cardiovascular magnetic resonane in immune checkpoint inhibitor-associated myocarditis. Eur Heart J. 2020;18(7):1733–43.

    Article  Google Scholar 

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Authors and Affiliations

  1. Division of Cardiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, 19104, USA

    Marwa Soltani, Lara J. Sokoloff & Michael G. Fradley

  2. Perelman Center for Advanced Medicine East Pavilion 2nd Floor, 3400 Civic Center Boulevard, Philadelphia, PA, 19104, USA

    Marwa Soltani & Michael G. Fradley

  3. Department of Medicine, Hospital of the University of Pennsylvania, 3400 Spruce Street, 100 Centrex, Philadelphia, PA, 19104, USA

    Lara J. Sokoloff

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  1. Marwa Soltani
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Soltani, M., Sokoloff, L.J. & Fradley, M.G. Cardiotoxicities of Non-Chemotherapeutic Metastatic Breast Cancer Treatments. Curr Oncol Rep 25, 923–935 (2023). https://doi.org/10.1007/s11912-023-01427-z

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