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Optimal outcomes for liver-dominant metastatic breast cancer with transarterial chemoembolization with drug-eluting beads loaded with doxorubicin

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Abstract

The purpose of this study was to evaluate the efficacy of image-guided delivery of locoregional chemotherapy to breast cancer hepatic metastases using doxorubicin-loaded drug-eluting beads (DEBDOX). An IRB-approved multi-center, prospective, open, non-controlled repeat treatment registry to investigate the safety and efficacy of doxorubicin microspheres in the treatment of patients with unresectable liver metastasis from breast cancer was reviewed. Statistical analysis was performed with differences of P < 0.05 considered significant. About 40 patients with metastatic breast cancer (MBC) to the liver underwent a total of 75 image-guided procedures with hepatic arterial drug-eluting beads loaded with doxorubicin (DEBDOX). Treatment was well tolerated with a total of eight patients sustaining 13 adverse events within the 30 days of each treatment session. All adverse events were either a grade I or grade II in toxicity. After a median follow-up of 12 months in all patients, the hepatic progression-free survival was a median of 26 months and overall survival was a median of 47 months. The treatment of hepatic metastasis from MBC using DEBDOX is an effective local therapy with very high response rates and a very safe toxicity profile. In comparison to chemotherapy alone, consideration of hepatic-directed therapy is warranted in patients with liver-dominant metastatic disease.

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References

  1. Hoe AL, Royle GT, Taylor I (1991) Breast liver metastases—incidence, diagnosis and outcome. J.R.Soc.Med. 84:714–716

    PubMed  CAS  Google Scholar 

  2. Bos R, Der Hoeven JJ, van Der WE et al (2002) Biologic correlates of (18)fluorodeoxyglucose uptake in human breast cancer measured by positron emission tomography. J.Clin.Oncol 20:379–387

    Article  PubMed  CAS  Google Scholar 

  3. Bathe OF, Kaklamanos IG, Moffat FL et al (1999) Metastasectomy as a cytoreductive strategy for treatment of isolated pulmonary and hepatic metastases from breast cancer. Surg Oncol 8:35–42

    Article  PubMed  CAS  Google Scholar 

  4. Zinser JW, Hortobagyi GN, Buzdar AU et al (1987) Clinical course of breast cancer patients with liver metastases. J.Clin.Oncol. 5:773–782

    PubMed  CAS  Google Scholar 

  5. Vogl TJ, Naguib NN, Nour-Eldin NE et al (2010) Transarterial chemoembolization (TACE) with mitomycin C and gemcitabine for liver metastases in breast cancer. Eur.Radiol. 20:173–180

    Article  PubMed  Google Scholar 

  6. Brown DB, Gould JE, Gervais DA et al (2009) Transcatheter therapy for hepatic malignancy: standardization of terminology and reporting criteria. J.Vasc.Interv.Radiol. 20:S425–S434

    Article  PubMed  Google Scholar 

  7. Adam R, Aloia T, Krissat J et al (2006) Is liver resection justified for patients with hepatic metastases from breast cancer? Ann Surg 244:897–907 discussion 907-898

    Article  PubMed  Google Scholar 

  8. Vlastos G, Smith DL, Singletary SE et al (2004) Long-term survival after an aggressive surgical approach in patients with breast cancer hepatic metastases. Ann Surg Oncol 11:869–874

    Article  PubMed  Google Scholar 

  9. Elias D, Maisonnette F, Druet-Cabanac M et al (2003) An attempt to clarify indications for hepatectomy for liver metastases from breast cancer. Am J Surg 185:158–164

    Article  PubMed  Google Scholar 

  10. Yoshimoto M, Tada T, Saito M et al (2000) Surgical treatment of hepatic metastases from breast cancer. Breast Cancer Res Treat 59:177–184

    Article  PubMed  CAS  Google Scholar 

  11. Pocard M, Pouillart P, Asselain B, Salmon R (2000) Hepatic resection in metastatic breast cancer: results and prognostic factors. Eur.J.Surg.Oncol. 26:155–159

    Article  PubMed  CAS  Google Scholar 

  12. Maksan SM, Lehnert T, Bastert G, Herfarth C (2000) Curative liver resection for metastatic breast cancer. Eur.J.Surg.Oncol. 26:209–212

    Article  PubMed  CAS  Google Scholar 

  13. Lawes D, Chopada A, Gillams A et al (2006) Radiofrequency ablation (RFA) as a cytoreductive strategy for hepatic metastasis from breast cancer. Ann R Coll Surg Engl 88:639–642

    Article  PubMed  CAS  Google Scholar 

  14. Poon RT, Tso WK, Pang RW et al (2007) A phase I/II trial of chemoembolization for hepatocellular carcinoma using a novel intra-arterial drug-eluting bead. Clin.Gastroenterol.Hepatol. 5:1100–1108

    Article  PubMed  CAS  Google Scholar 

  15. Fiorentini G, Aliberti C, Turrisi G et al (2007) Intraarterial hepatic chemoembolization of liver metastases from colorectal cancer adopting irinotecan-eluting beads: results of a phase II clinical study. In Vivo 21:1085–1091

    PubMed  CAS  Google Scholar 

  16. Lewis AL, Gonzalez MV, Lloyd AW et al (2006) DC bead: in vitro characterization of a drug-delivery device for transarterial chemoembolization. J Vasc.Interv.Radiol. 17:335–342

    Article  PubMed  Google Scholar 

  17. Lewis AL, Gonzalez MV, Leppard SW et al (2007) Doxorubicin eluting beads-1: effects of drug loading on bead characteristics and drug distribution. J Mater.Sci.Mater.Med. 18:1691–1699

    Article  PubMed  CAS  Google Scholar 

  18. Lewis AL, Taylor RR, Hall B et al (2006) Pharmacokinetic and safety study of doxorubicin-eluting beads in a porcine model of hepatic arterial embolization. J Vasc.Interv.Radiol. 17:1335–1343

    Article  PubMed  Google Scholar 

  19. Lammer J, Malagari K, Vogl T et al (2010) Prospective randomized study of doxorubicin-eluting-bead embolization in the treatment of hepatocellular carcinoma: results of the PRECISION V study. Cardiovasc.Intervent.Radiol. 33:41–52

    Article  PubMed  Google Scholar 

  20. Joshi J, Roberts K, Valek V, Boudny J, Andrasina T, Padr R, Hara R, Tomalty D, Martin RCG (2010) Transarterial chemoembolization with drug-eluting beads loaded with doxorubicin for the treatment of metastatic breast cancer to the liver: results from a multi-institutional registry. J Interventional Oncol 3:114–123

    Google Scholar 

  21. Levine MN, Julian JA (2008) Registries that show efficacy: good, but not good enough. J.Clin Oncol. 26:5316–5319

    Article  PubMed  Google Scholar 

  22. Sacks D, Marinelli DL, Martin LG, Spies JB (2003) General principles for evaluation of new interventional technologies and devices. J.Vasc.Interv.Radiol. 14:S391–S394

    Article  PubMed  Google Scholar 

  23. Lencioni R, Llovet JM (2010) Modified RECIST (mRECIST) assessment for hepatocellular carcinoma. Semin.Liver Dis. 30:52–60

    Article  PubMed  CAS  Google Scholar 

  24. Cardella JF, Kundu S, Miller DL et al (2009) Society of interventional radiology clinical practice guidelines. J.Vasc.Interv.Radiol. 20:S189–S191

    Article  PubMed  Google Scholar 

  25. Brewster AM, Hortobagyi GN, Broglio KR et al (2008) Residual risk of breast cancer recurrence 5 years after adjuvant therapy. J.Natl.Cancer Inst. 100:1179–1183

    Article  PubMed  Google Scholar 

  26. De Laurentiis M, Cancello G, D’Agostino D et al (2008) Taxane-based combinations as adjuvant chemotherapy of early breast cancer: a meta-analysis of randomized trials. J.Clin.Oncol 26:44–53

    Article  PubMed  Google Scholar 

  27. Wong ST, Goodin S (2009) Overcoming drug resistance in patients with metastatic breast cancer. Pharmacotherapy 29:954–965

    Article  PubMed  CAS  Google Scholar 

  28. Beslija S, Bonneterre J, Burstein HJ et al (2009) Third consensus on medical treatment of metastatic breast cancer. Ann.Oncol 20:1771–1785

    Article  PubMed  CAS  Google Scholar 

  29. Ershler WB (2006) Capecitabine monotherapy: safe and effective treatment for metastatic breast cancer. Oncologist. 11:325–335

    Article  PubMed  CAS  Google Scholar 

  30. Puhalla S, Brufsky A (2008) Ixabepilone: a new chemotherapeutic option for refractory metastatic breast cancer. Biologics. 2:505–515

    PubMed  CAS  Google Scholar 

  31. Elias AD, Mazanet R, Wheeler C et al (1991) GM-CSF potentiated peripheral blood progenitor cell (PBPC) collection with or without bone marrow as hematologic support of high-dose chemotherapy: two protocols. Breast Cancer Res.Treat. 20(Suppl):S25–S29

    Article  PubMed  Google Scholar 

  32. Schneebaum S, Walker MJ, Young D et al (1994) The regional treatment of liver metastases from breast cancer. J.Surg Oncol 55:26–31

    Article  PubMed  CAS  Google Scholar 

  33. Lubrano J, Roman H, Tarrab S et al (2008) Liver resection for breast cancer metastasis: does it improve survival? Surg Today 38:293–299

    Article  PubMed  Google Scholar 

  34. Martin RC, Robbins K, Tomalty D et al (2009) Transarterial chemoembolisation (TACE) using irinotecan-loaded beads for the treatment of unresectable metastases to the liver in patients with colorectal cancer: an interim report. World J Surg Oncol 7:80

    Article  PubMed  Google Scholar 

  35. Amersi FF, McElrath-Garza A, Ahmad A et al (2006) Long-term survival after radiofrequency ablation of complex unresectable liver tumors. Arch Surg 141:581–587 discussion 587-588

    Article  PubMed  Google Scholar 

  36. Hoffmann RT, Jakobs TF, Kubisch CH et al (2010) Radiofrequency ablation after selective internal radiation therapy with Yttrium90 microspheres in metastatic liver disease—is it feasible? Eur.J.Radiol. 74:199–205

    Article  PubMed  CAS  Google Scholar 

  37. Diamond JR, Finlayson CA, Borges VF (2009) Hepatic complications of breast cancer. Lancet Oncol 10:615–621

    Article  PubMed  Google Scholar 

  38. Baselga J, Tripathy D, Mendelsohn J et al (1999) Phase II study of weekly intravenous trastuzumab (Herceptin) in patients with HER2/neu-overexpressing metastatic breast cancer. Semin.Oncol 26:78–83

    PubMed  CAS  Google Scholar 

  39. Sanchez-Rovira P, Jaen A, Gonzalez E et al (2001) Biweekly gemcitabine, doxorubicin, and paclitaxel as first-line treatment in metastatic breast cancer. Final results from a phase II trial. Oncology 15:44–47

    PubMed  CAS  Google Scholar 

  40. Selzner M, Morse MA, Vredenburgh JJ et al (2000) Liver metastases from breast cancer: long-term survival after curative resection. Surgery 127:383–389

    Article  PubMed  CAS  Google Scholar 

  41. Carlini M, Lonardo MT, Carboni F et al (2002) Liver metastases from breast cancer. Results of surgical resection. Hepatogastroenterology 49:1597–1601

    PubMed  Google Scholar 

  42. Sakamoto Y, Yamamoto J, Yoshimoto M et al (2005) Hepatic resection for metastatic breast cancer: prognostic analysis of 34 patients. World J Surg 29:524–527

    Article  PubMed  Google Scholar 

  43. d’Annibale M, Piovanello P, Cerasoli V, Campioni N (2005) Liver metastases from breast cancer: the role of surgical treatment. Hepatogastroenterology 52:1858–1862

    PubMed  Google Scholar 

  44. Adam R, Chiche L, Aloia T et al (2006) Hepatic resection for noncolorectal nonendocrine liver metastases: analysis of 1,452 patients and development of a prognostic model. Ann Surg 244:524–535

    Article  PubMed  Google Scholar 

  45. Caralt M, Bilbao I, Cortes J et al (2008) Hepatic resection for liver metastases as part of the “oncosurgical” treatment of metastatic breast cancer. Ann Surg Oncol 15:2804–2810

    Article  PubMed  Google Scholar 

  46. Furka A, Halasz L, Szentkereszty Z et al (2008) Surgical treatment of liver metastases from breast cancer. Hepatogastroenterology 55:1416–1418

    PubMed  CAS  Google Scholar 

  47. Li XP, Meng ZQ, Guo WJ, Li J (2005) Treatment for liver metastases from breast cancer: results and prognostic factors. World journal of gastroenterology : WJG 11:3782–3787

    PubMed  Google Scholar 

  48. Giroux MF, Baum RA, Soulen MC (2004) Chemoembolization of liver metastasis from breast carcinoma. Journal of vascular and interventional radiology : JVIR 15:289–291

    Article  PubMed  Google Scholar 

  49. Vogl TJ, Mack MG, Balzer JO et al (2003) Liver metastases: neoadjuvant downsizing with transarterial chemoembolization before laser-induced thermotherapy. Radiology 229:457–464

    Article  PubMed  Google Scholar 

  50. Meloni MF, Andreano A, Laeseke PF et al (2009) Breast cancer liver metastases: US-guided percutaneous radiofrequency ablation—intermediate and long-term survival rates. Radiology 253:861–869

    Article  PubMed  Google Scholar 

  51. Ikeda T, Adachi I, Takashima S et al (1999) A phase I/II study of continuous intra-arterial chemotherapy using an implantable reservoir for the treatment of liver metastases from breast cancer: a Japan Clinical Oncology Group (JCOG) study 9113. JCOG Breast Cancer Study Group. Jpn J Clin Oncol 29:23–27

    Article  PubMed  CAS  Google Scholar 

  52. Camacho LH, Kurzrock R, Cheung A et al (2007) Pilot study of regional, hepatic intra-arterial paclitaxel in patients with breast carcinoma metastatic to the liver. Cancer 109:2190–2196

    Article  PubMed  CAS  Google Scholar 

  53. Maes T, Wildiers H, Heye S et al (2008) Intra-hepatic Mitomycin C bolus infusion in the treatment of extensive liver metastases of breast cancer. Breast Cancer Res Treat 110:135–142

    Article  PubMed  CAS  Google Scholar 

  54. Gulec SA, Mesoloras G, Dezarn WA et al (2007) Safety efficacy of Y-90 microsphere treatment in patients with primary, metastatic liver cancer: the tumor selectivity of the treatment as a function of tumor to liver flow ratio. Journal of translational medicine 5:15

    Article  PubMed  Google Scholar 

  55. Visonneau S, Cesano A, Porter DL et al (2000) Phase I trial of TALL-104 cells in patients with refractory metastatic breast cancer. Clinical cancer research : an official journal of the American Association for Cancer Research 6:1744–1754

    CAS  Google Scholar 

  56. Mavroudis D, Malamos N, Alexopoulos A et al (1999) Salvage chemotherapy in anthracycline-pretreated metastatic breast cancer patients with docetaxel and gemcitabine: a multicenter phase II trial. Greek Breast Cancer Cooperative Group. Annals of oncology : official journal of the European Society for Medical Oncology/ESMO 10:211–215

    Article  CAS  Google Scholar 

  57. Baselga J, Tripathy D, Mendelsohn J et al (1999) Phase II study of weekly intravenous trastuzumab (Herceptin) in patients with HER2/neu-overexpressing metastatic breast cancer. Semin Oncol 26:78–83

    PubMed  CAS  Google Scholar 

  58. Alexandre J, Bleuzen P, Bonneterre J et al (2000) Factors predicting for efficacy and safety of docetaxel in a compassionate-use cohort of 825 heavily pretreated advanced breast cancer patients. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 18:562–573

    CAS  Google Scholar 

  59. Atalay G, Biganzoli L, Renard F et al (2003) Clinical outcome of breast cancer patients with liver metastases alone in the anthracycline-taxane era: a retrospective analysis of two prospective, randomised metastatic breast cancer trials. Eur J Cancer 39:2439–2449

    Article  PubMed  CAS  Google Scholar 

  60. Mouridsen H, Chaudri-Ross HA (2004) Efficacy of first-line letrozole versus tamoxifen as a function of age in postmenopausal women with advanced breast cancer. The oncologist 9:497–506

    Article  PubMed  CAS  Google Scholar 

  61. Iba T, Kidokoro A, Fukunaga M et al (2004) The efficacy of long-term oral chemotherapy with 5′-deoxy-5-fluorouridine and cyclophosphamide for recurrent breast cancer. International journal of clinical oncology/Japan Society of Clinical Oncology 9:383–387

    Article  PubMed  CAS  Google Scholar 

  62. Stathopoulos GP, Tsavdaridis D, Malamos NA et al (2005) Irinotecan combined with docetaxel in pre-treated metastatic breast cancer patients: a phase II study. Cancer Chemother Pharmacol 56:487–491

    Article  PubMed  CAS  Google Scholar 

  63. Pentheroudakis G, Razis E, Athanassiadis A et al (2006) Paclitaxel-carboplatin combination chemotherapy in advanced breast cancer: accumulating evidence for synergy, efficacy, and safety. Med Oncol 23:147–160

    Article  PubMed  CAS  Google Scholar 

  64. Nishimura R, Okumura Y, Arima N (2008) Trastuzumab monotherapy versus combination therapy for treating recurrent breast cancer: time to progression and survival. Breast cancer 15:57–64

    Article  PubMed  Google Scholar 

  65. Er O, Frye DK, Kau SW et al (2008) Clinical course of breast cancer patients with metastases limited to the liver treated with chemotherapy. Cancer J 14:62–68

    Article  PubMed  Google Scholar 

  66. Tanabe M, Ito Y, Tokudome N et al (2009) Possible use of combination chemotherapy with mitomycin C and methotrexate for metastatic breast cancer pretreated with anthracycline and taxanes. Breast cancer 16:301–306

    Article  PubMed  Google Scholar 

  67. Kalbakis K, Kouroussis C, Kakolyris S et al (2001) Salvage chemotherapy with high-dose leucovorin (LV) and 48-hour continuous infusion (CI) of 5-fluorouracil (5-FU) in combination with conventional doses of cyclophosphamide (CPM) in patients with metastatic breast cancer (MBC) pretreated with anthracycline and taxanes. Br J Cancer 85:798–802

    Article  PubMed  CAS  Google Scholar 

  68. Airoldi M, Cattel L, Passera R et al (2006) Gemcitabine and oxaliplatin in patients with metastatic breast cancer resistant to or pretreated with both anthracyclines and taxanes: clinical and pharmacokinetic data. Am J Clin Oncol 29:490–494

    Article  PubMed  CAS  Google Scholar 

  69. Delozier T, Guastalla JP, Yovine A et al (2006) A phase II study of an oxaliplatin/vinorelbine/5-fluorouracil combination in patients with anthracycline-pretreated and taxane-pretreated metastatic breast cancer. Anti-cancer drugs 17:1067–1073

    Article  PubMed  CAS  Google Scholar 

  70. Blum JL, Savin MA, Edelman G et al (2007) Phase II study of weekly albumin-bound paclitaxel for patients with metastatic breast cancer heavily pretreated with taxanes. Clinical breast cancer 7:850–856

    Article  PubMed  CAS  Google Scholar 

  71. Onyenadum A, Gogas H, Markopoulos C et al (2007) Mitoxantrone plus vinorelbine in pretreated patients with metastatic breast cancer. J Chemother 19:582–589

    PubMed  CAS  Google Scholar 

  72. Thomas E, Tabernero J, Fornier M et al (2007) Phase II clinical trial of ixabepilone (BMS-247550), an epothilone B analog, in patients with taxane-resistant metastatic breast cancer. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 25:3399–3406

    Article  CAS  Google Scholar 

  73. Garin A, Manikhas A, Biakhov M et al (2008) A phase II study of pemetrexed and carboplatin in patients with locally advanced or metastatic breast cancer. Breast Cancer Res Treat 110:309–315

    Article  PubMed  CAS  Google Scholar 

  74. Campora E, Colloca G, Ratti R et al (2008) Docetaxel for metastatic breast cancer: two consecutive phase II trials. Anticancer Res 28:3993–3995

    PubMed  CAS  Google Scholar 

  75. Tan WW, Hillman DW, Salim M et al (2010) N0332 phase 2 trial of weekly irinotecan hydrochloride and docetaxel in refractory metastatic breast cancer: a North Central Cancer Treatment Group (NCCTG) Trial. Annals of oncology : official journal of the European Society for Medical Oncology/ESMO 21:493–497

    Article  CAS  Google Scholar 

  76. Polyzos A, Gogas H, Markopoulos C et al (2009) Salvage chemotherapy with oxaliplatin and capecitabine for breast cancer patients pretreated with anthracyclines and taxanes. Anticancer Res 29:2851–2856

    PubMed  CAS  Google Scholar 

  77. Tubiana-Mathieu N, Bougnoux P, Becquart D et al (2009) All-oral combination of oral vinorelbine and capecitabine as first-line chemotherapy in HER2-negative metastatic breast cancer: an International Phase II Trial. Br J Cancer 101:232–237

    Article  PubMed  CAS  Google Scholar 

  78. Sparano JA, Makhson AN, Semiglazov VF et al (2009) Pegylated liposomal doxorubicin plus docetaxel significantly improves time to progression without additive cardiotoxicity compared with docetaxel monotherapy in patients with advanced breast cancer previously treated with neoadjuvant-adjuvant anthracycline therapy: results from a randomized phase III study. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 27:4522–4529

    Article  CAS  Google Scholar 

  79. Yardley DA, Burris HA 3rd, Hanson S et al (2009) Weekly gemcitabine and trastuzumab in the treatment of patients with HER2-overexpressing metastatic breast cancer. Clinical breast cancer 9:178–183

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Division of Surgical Oncology, Department of Surgery, University of Louisville School of Medicine, Louisville, KY, 40292, USA

    Robert C. G. Martin

  2. Baptist Health, Little Rock, AR, USA

    Ken Robbins

  3. Hospital Parc Taulí de Sabadell, Sabadell, Barcelona, Spain

    Joan Falcó Fagés

  4. Hospital Universitario de Canarias, Tenerife, Spain

    Francisco Diaz Romero

  5. University of Maine, Orono, ME, USA

    Lisa Rustein

  6. Huntsville Hospital, Huntsville, AL, USA

    Dana Tomalty

  7. Hospital Italiano, Universidad de Buenos Aires, Buenos Aires, Argentina

    Ricardo Monaco

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  1. Robert C. G. Martin
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Correspondence to Robert C. G. Martin.

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Martin, R.C.G., Robbins, K., Fagés, J.F. et al. Optimal outcomes for liver-dominant metastatic breast cancer with transarterial chemoembolization with drug-eluting beads loaded with doxorubicin. Breast Cancer Res Treat 132, 753–763 (2012). https://doi.org/10.1007/s10549-011-1926-z

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