Skip to main content

Advertisement

Log in

Fatal hepatitis B reactivation due to everolimus in metastatic breast cancer: case report and review of literature

  • Review
  • Published:
Breast Cancer Research and Treatment Aims and scope Submit manuscript

Abstract

Hepatitis B reactivation can occur with cytotoxic chemotherapy in patients with hepatitis B and cancer. Reactivation can occur in a patient with chronic hepatitis, an inactive carrier, or one with resolved hepatitis. Clinical presentation may range from subclinical elevation of liver enzymes to fatal fulminant hepatic failure. Mammalian target of rapamycin inhibitors, which include everolimus, are a new generation of targeted agents that are currently approved for many cancers (since March 2009) including advanced hormone receptor positive, human epidermal growth factor receptor 2-negative breast cancer, in conjunction with exemestane (as of July 2012). We are therefore still learning the various adverse events that occur with this new class of agents. Here, we present an unfortunate case of fatal hepatitis B reactivation in a woman with metastatic breast cancer treated with everolimus and exemestane. We have detailed the controversies around hepatitis B screening prior to immunosuppressive therapy. Clinicians and patients should be aware of this rare but fatal complication prior to everolimus use, and a detailed history, screening for hepatitis B and prophylactic antiviral treatment should be considered.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Baselga J, Campone M, Piccart M, Burris HA 3rd, 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, Xu Z, Mukhopadhyay P, Lebwohl D, Hortobagyi GN (2012) Everolimus in postmenopausal hormone-receptor-positive advanced breast cancer. N Engl J Med 366(6):520–529. doi:10.1056/NEJMoa1109653

    Article  PubMed  CAS  Google Scholar 

  2. Pazdur R (2013) FDA Approval of everolimus. http://www.cancer.gov/cancertopics/druginfo/fda-everolimus. Accessed 15 Aug 2013

  3. AFINITOR Package insert. Novartis Pharma

  4. Sezgin Goksu S, Bilal S, Coskun HS (2013) Hepatitis B reactivation related to everolimus. World J Hepatol 5(1):43–45. doi:10.4254/wjh.v5.i1.43

    Article  PubMed  Google Scholar 

  5. Mizuno S, Yamagishi Y, Ebinuma H, Nakamoto N, Katahira M, Sasaki A, Sakamoto M, Suzuki H, Kanai T, Hibi T (2013) Progressive liver failure induced by everolimus for renal cell carcinoma in a 58-year-old male hepatitis B virus carrier. Clin J Gastroenterol 6(2):188–192. doi:10.1007/s12328-013-0371-4

    Article  PubMed  Google Scholar 

  6. Yao JC, Shah MH, Ito T, Bohas CL, Wolin EM, Van Cutsem E, Hobday TJ, Okusaka T, Capdevila J, de Vries EG, Tomassetti P, Pavel ME, Hoosen S, Haas T, Lincy J, Lebwohl D, Oberg K, Rad001 in Advanced Neuroendocrine Tumors TTSG (2011) Everolimus for advanced pancreatic neuroendocrine tumors. New Eng J Med 364(6):514–523. doi:10.1056/NEJMoa1009290

    Article  PubMed  CAS  Google Scholar 

  7. Krueger DA, Care MM, Holland K, Agricola K, Tudor C, Mangeshkar P, Wilson KA, Byars A, Sahmoud T, Franz DN (2010) Everolimus for subependymal giant-cell astrocytomas in tuberous sclerosis. New Eng J Med 363(19):1801–1811. doi:10.1056/NEJMoa1001671

    Article  PubMed  CAS  Google Scholar 

  8. Franz DN, Belousova E, Sparagana S, Bebin EM, Frost M, Kuperman R, Witt O, Kohrman MH, Flamini JR, Wu JY, Curatolo P, de Vries PJ, Whittemore VH, Thiele EA, Ford JP, Shah G, Cauwel H, Lebwohl D, Sahmoud T, Jozwiak S (2013) Efficacy and safety of everolimus for subependymal giant cell astrocytomas associated with tuberous sclerosis complex (EXIST-1): a multicentre, randomised, placebo-controlled phase 3 trial. Lancet 381(9861):125–132. doi:10.1016/S0140-6736(12)61134-9

    Article  PubMed  CAS  Google Scholar 

  9. Motzer RJ, Escudier B, Oudard S, Hutson TE, Porta C, Bracarda S, Grunwald V, Thompson JA, Figlin RA, Hollaender N, Urbanowitz G, Berg WJ, Kay A, Lebwohl D, Ravaud A, Group R-S (2008) Efficacy of everolimus in advanced renal cell carcinoma: a double-blind, randomised, placebo-controlled phase III trial. Lancet 372(9637):449–456. doi:10.1016/S0140-6736(08)61039-9

    Article  PubMed  CAS  Google Scholar 

  10. Oketani M, Ido A, Uto H, Tsubouchi H (2012) Prevention of hepatitis B virus reactivation in patients receiving immunosuppressive therapy or chemotherapy. Hepatol Res 42(7):627–636. doi:10.1111/j.1872-034X.2012.00998.x

    Article  PubMed  CAS  Google Scholar 

  11. Maynard JE (1990) Hepatitis B: global importance and the need for control. Vaccine 8 (Suppl):S18–S20

    Article  Google Scholar 

  12. Lok ASF, McMahon BJ (2009) AASLD Practice guideline update: chronic hepatitis B: update 2009. http://www.aasld.org/practiceguidelines/Documents/Bookmarked%20Practice%20Guidelines/Chronic_Hep_B_Update_2009%208_24_2009.10.1007/s10549-013-2681-0. Accessed 15 Aug 2013

  13. Kowdley KVWCC, Welch S, Roberts H, Brosgart CL (2012) Prevalence of chronic hepatitis B among foreign-born persons living in the United States by country of origin. Hepatology 56(2):422–433. doi:10.1002/hep.24804

    Article  PubMed  Google Scholar 

  14. Yeo W, Chan PK, Hui P, Ho WM, Lam KC, Kwan WH, Zhong S, Johnson PJ (2003) Hepatitis B virus reactivation in breast cancer patients receiving cytotoxic chemotherapy: a prospective study. J Med Virol 70(4):553–561. doi:10.1002/jmv.10430

    Article  PubMed  Google Scholar 

  15. Shoushtari AH, Shaw RA (2013) Fulminant hepatitis following chemotherapy treatment for breast cancer. BMJ Case Rep. doi:10.1136/bcr-2012-007017

    PubMed  Google Scholar 

  16. Lok AS, Liang RH, Chiu EK, Wong KL, Chan TK, Todd D (1991) Reactivation of hepatitis B virus replication in patients receiving cytotoxic therapy. Report of a prospective study. Gastroenterology 100(1):182–188

    PubMed  CAS  Google Scholar 

  17. Hoofnagle JH (2009) Reactivation of hepatitis B. Hepatology 49(5 Suppl):S156–S165. doi:10.1002/hep.22945

    Article  PubMed  CAS  Google Scholar 

  18. Marzano A, Angelucci E, Andreone P, Brunetto M, Bruno R, Burra P, Caraceni P, Daniele B, Di Marco V, Fabrizi F, Fagiuoli S, Grossi P, Lampertico P, Meliconi R, Mangia A, Puoti M, Raimondo G, Smedile A, Italian Association for the Study of the Liver (2007) Prophylaxis and treatment of hepatitis B in immunocompromised patients. Dig Liver Dis 39(5):397–408. doi:10.1016/j.dld.2006.12.017

    Article  PubMed  CAS  Google Scholar 

  19. Matsue K, Kimura S, Takanashi Y, Iwama K, Fujiwara H, Yamakura M, Takeuchi M (2010) Reactivation of hepatitis B virus after rituximab-containing treatment in patients with CD20-positive B-cell lymphoma. Cancer 116(20):4769–4776. doi:10.1002/cncr.25253

    Article  PubMed  Google Scholar 

  20. Knoll A, Boehm S, Hahn J, Holler E, Jilg W (2004) Reactivation of resolved hepatitis B virus infection after allogeneic haematopoietic stem cell transplantation. Bone Marrow Transplant 33(9):925–929. doi:10.1038/sj.bmt.1704457

    Article  PubMed  CAS  Google Scholar 

  21. Ling WH, Soe PP, Pang AS, Lee SC (2013) Hepatitis B virus reactivation risk varies with different chemotherapy regimens commonly used in solid tumours. Br J Cancer 108(10):1931–1935. doi:10.1038/bjc.2013.225

    Article  PubMed  CAS  Google Scholar 

  22. Onozawa M, Hashino S, Izumiyama K, Kahata K, Chuma M, Mori A, Kondo T, Toyoshima N, Ota S, Kobayashi S, Hige S, Toubai T, Tanaka J, Imamura M, Asaka M (2005) Progressive disappearance of anti-hepatitis B surface antigen antibody and reverse seroconversion after allogeneic hematopoietic stem cell transplantation in patients with previous hepatitis B virus infection. Transplantation 79(5):616–619

    Article  PubMed  Google Scholar 

  23. Yeo W, Zee B, Zhong S, Chan PK, Wong WL, Ho WM, Lam KC, Johnson PJ (2004) Comprehensive analysis of risk factors associating with Hepatitis B virus (HBV) reactivation in cancer patients undergoing cytotoxic chemotherapy. Br J Cancer 90(7):1306–1311. doi:10.1038/sj.bjc.6601699

    Article  PubMed  CAS  Google Scholar 

  24. Manzano-Alonso ML, Castellano-Tortajada G (2011) Reactivation of hepatitis B virus infection after cytotoxic chemotherapy or immunosuppressive therapy. World J Gastroenterol 17(12):1531–1537. doi:10.3748/wjg.v17.i12.1531

    Article  PubMed  CAS  Google Scholar 

  25. Teng CF, Wu HC, Tsai HW, Shiah HS, Huang W, Su IJ (2011) Novel feedback inhibition of surface antigen synthesis by mammalian target of rapamycin (mTOR) signal and its implication for hepatitis B virus tumorigenesis and therapy. Hepatology 54(4):1199–1207. doi:10.1002/hep.24529

    Article  PubMed  CAS  Google Scholar 

  26. Recommendations for routine testing and follow-up for chronic hepatitis B virus (HBV) infection. Centers for disease control and prevention. http://www.cdc.gov/hepatitis/hbv/PDFs/ChronicHepBTestingFlwUp.pdf. Accessed 15 Aug 2013

  27. Artz AS, Somerfield MR, Feld JJ, Giusti AF, Kramer BS, Sabichi AL, Zon RT, Wong SL (2010) American society of clinical oncology provisional clinical opinion: chronic hepatitis B virus infection screening in patients receiving cytotoxic chemotherapy for treatment of malignant diseases. J Clin Oncol 28(19):3199–3202. doi:10.1200/JCO.2010.30.0673

    Article  PubMed  Google Scholar 

  28. Everolimus (RAD001) in Metastatic transitional cell carcinoma of the urothelium, NCT00805129. http://clinicaltrials.gov/show/NCT00805129. Accessed 15 Aug 2013

  29. Study of everolimus added to combined hormonal and radiation therapy for high risk prostate cancer, NCT01642732. http://clinicaltrials.gov/show/NCT01642732. Accessed 15 Aug 2013

  30. Everolimus plus best supportive care versus placebo plus best supportive care in the treatment of patients with advanced neuroendocrine tumors (GI or Lung Origin) (RADIANT-4), NCT01524783. http://clinicaltrials.gov/show/NCT01524783. Accessed 15 Aug 2013

  31. S1207 Hormone therapy with or without everolimus in treating patients with breast cancer, NCT01674140.. http://clinicaltrials.gov/ct2/show/NCT01674140?term=swog+1207&rank=1. Accessed 15 Aug 2013

  32. Phase III Study of RAD001 Adjuvant Therapy in poor risk patients with diffuse large B-cell lymphoma (DLBCL) of RAD001 versus matching placebo After patients have achieved complete response with first-line rituximab-chemotherapy (PILLAR2), NCT00790036. http://clinicaltrials.gov/show/NCT00790036. Accessed 15 Aug 2013

  33. Daily everolimus in combination with trastuzumab and vinorelbine in HER2/neu positive women with locally advanced or metastatic breast cancer (BOLERO-3), NCT01007942.http://clinicaltrials.gov/show/NCT01007942. Accessed 15 Aug 2013

  34. Open-label, phase II, study of everolimus plus letrozole in postmenopausal women with ER+Metastatic breast cancer (Bolero-4), NCT01698918. http://clinicaltrials.gov/show/NCT01698918. Accessed 15 Aug 2013

  35. A phase II study of everolimus in combination with exemestane versus everolimus alone versus capecitabine in advance breast cancer. (BOLERO-6), NCT01783444. http://clinicaltrials.gov/show/NCT01783444. Accessed 15 Aug 2013

  36. Porta C, Osanto S, Ravaud A, Climent M-A, Vaishampayan U, White DA, Creel P, Dickow B, Fischer P, Gornell SS, Meloni F, Motzer RJ (2011) Management of adverse events associated with the use of everolimus in patients with advanced renal cell carcinoma. Eur J Cancer 47(9):1287–1298. doi:10.1016/j.ejca.2011.02.014

    Article  PubMed  CAS  Google Scholar 

  37. European Association for the Study of the Liver (2009) Clinical practice guidelines: management of chronic hepatitis B. J Hepatol 50(2):227–242. doi:10.1016/j.jhep.2008.10.001

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Komal Jhaveri.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Teplinsky, E., Cheung, D., Weisberg, I. et al. Fatal hepatitis B reactivation due to everolimus in metastatic breast cancer: case report and review of literature. Breast Cancer Res Treat 141, 167–172 (2013). https://doi.org/10.1007/s10549-013-2681-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10549-013-2681-0

Keywords

Navigation