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Autografting

Long-term survival in patients with metastatic breast cancer receiving intensified chemotherapy and stem cell rescue: data from the Italian registry

Abstract

The median survival of women with metastatic breast cancer (MBC) is 18–24 months, and fewer than 5% are alive and disease free at 5 years. We report toxicity and survival in a cohort of MBC patients receiving high-dose chemotherapy (HDC) with autologous hematopoietic SCT (AHSCT) in Italy between 1990 and 2005. Data set for survival analysis has been obtained for 415 patients. Clinical parameters including probability of transplant-related mortality (TRM), PFS and OS. With a median follow-up of 27 months (range 0–172), OS and PFS at 5 and 10 years in the whole population were 47/23 and 32/14%, respectively. A total 239 patients are alive with a median follow-up of 33 months (range 2–174). Survival was significantly more pronounced in patients harboring hormone receptor positive tumors (P=0.028), without visceral metastases (P=0.009) and in women with chemosensitive disease (P<0.0001). Sixty eight patients (20.4%) who received HDC in partial response, stable or progressive disease underwent conversion to CR. TRM was 2.5% overall and 1.3% since 2000. Our findings suggest that could be a role for HDC and AHSCT in delaying disease progression and possibly cure a subset of MBC patient harboring chemosensitive tumors.

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References

  1. Greenberg PA, Hortobagyi GN, Smith TL, Ziegler LD, Frye DK, Buzdar AU . Long-term follow-up of patients with complete remission following combination chemotherapy for metastatic breast cancer. J Clin Oncol 1996; 14: 2197–2205.

    CAS  Article  Google Scholar 

  2. Stockler M, Wilcken NR, Ghersi D, Simes RJ . Systematic reviews of chemotherapy and endocrine therapy in metastatic breast cancer. Cancer Treat Rev 2000; 26: 151–168.

    CAS  Article  Google Scholar 

  3. Gennari A, Conte P, Rosso R, Orlandini C, Bruzzi P . Survival of metastatic breast carcinoma patients over a 20-year period: a retrospective analysis based on individual patient data from six consecutive studies. Cancer 2005; 104: 1742–1750.

    Article  Google Scholar 

  4. Peters WP, Shpall EJ, Jones RB, Olsen GA, Bast RC, Gockerman JP et al. High-dose combination alkylating agents with bone marrow support as initial treatment for metastatic breast cancer. J Clin Oncol 1988; 6: 1368–1376.

    CAS  Article  Google Scholar 

  5. Antman K, Ayash L, Elias A, Wheeler C, Hunt M, Eder JP et al. A phase II study of high-dose cyclophosphamide, thiotepa, and carboplatin with autologous marrow support in women with measurable advanced breast cancer responding to standard-dose therapy. J Clin Oncol 1992; 10: 102–110.

    CAS  Article  Google Scholar 

  6. Williams SF, Gilewski T, Mick R, Bitran JD 1992 High-dose consolidation therapy with autologous stem-cell rescue in stage IV breast cancer: follow-up report. J Clin Oncol 1992; 10: 1743–1747.

    CAS  Article  Google Scholar 

  7. Kennedy MJ, Beveridge RA, Rowley SD, Gordon GB, Abeloff MD, Davidson NE . High-dose chemotherapy with reinfusion of purged autologous bone marrow following dose intense induction as initial therapy for metastatic breast cancer. J Natl Cancer Inst 1991; 83: 920–926.

    CAS  Article  Google Scholar 

  8. Lazarus HM . Hematopoietic progenitor cell transplantation in breast cancer: Current status and future directions. Cancer Invest 1998; 16: 102–126.

    CAS  Article  Google Scholar 

  9. Crown J . High-dose chemotherapy of metastatic breast cancer: the end of the beginning? Br J Cancer 1997; 75: 467–479.

    CAS  Article  Google Scholar 

  10. Siena S, Schiavo R, Pedrazzoli P, Carlo-Stella C . Therapeutic relevance of CD34 cell dose in blood cell transplantation for cancer therapy. J Clin Oncol 2000; 18: 1360–1377.

    CAS  Article  Google Scholar 

  11. Stadtmauer EA, O'Neill A, Goldstein LJ, Crilley PA, Mangan KF, Ingle JN et al. Conventional-dose chemotherapy compared with high-dose chemotherapy plus autologous hematopoietic stem-cell transplantation for metastatic breast cancer. N Engl J Med 2000; 342: 1069–1076.

    CAS  Article  Google Scholar 

  12. Crump M, Gluck S, Stewart D, Levine M, Pritchard K, Kirkbride P et al. A randomized trial of high-dose chemotherapy (HDC) with autologous peripheral blood stem cell support (ASCT) compared to standard therapy in women with metastatic breast cancer: a National Cancer Institute of Canada (NCIC) Clinical Trials Group study. Proc Am Soc Clin Oncol 2001; 20: (abstract 82).

  13. Crown JP, Leyvraz S, Verrill M, Guillem V, Efremidis A, Garcia-Conde Bru J et al. Effect of tandem high-dose chemotherapy (HDC) on long-term complete remissions (LTCR) in metastatic breast cancer (MBC), compared to conventional dose (CDC) in patients (pts) who were not selected on the basis of response to prior C: mature results of the IBDIS-I. J Clin Oncol, ASCO Annual Meeting Proceedings (Post-Meeting Edition) 2004; 22: 631 (July 15 Supplement).

    Google Scholar 

  14. Roche H, Viens P, Biron P, Lotz JP, Asselain B . PEGASE Group. High-dose chemotherapy for breast cancer: the French PEGASE experience. Cancer Control 2003; 10: 42–47.

    Article  Google Scholar 

  15. Schmid P, Schippinger W, Nitsch T, Huebner G, Heilmann V, Schultze W et al. Up-front tandem high-dose chemotherapy compared with standard chemotherapy with doxorubicin and paclitaxel in metastatic breast cancer: results of a randomized trial. J Clin Oncol 2005; 23: 432–440.

    CAS  Article  Google Scholar 

  16. Vredenburgh JJ, Coniglio D, Broadwater G, Jones RB, Ross M, Shpall EJ et al. Consolidation with high-dose combination alkylating agents with bone marrow transplantation significantly improves disease-free survival in hormone-insensitive metastatic breast cancer in complete remission compared with intensive standard-dose chemotherapy alone. Biol Blood Marrow Transplant 2006; 12: 195–203.

    CAS  Article  Google Scholar 

  17. Weiss RB, Gill GG, Hudis CA . An on-site audit of the South African trial of high-dose chemotherapy for metastatic breast cancer and associated publications. J Clin Oncol 2001; 19: 2771–2777.

    CAS  Article  Google Scholar 

  18. Berry DA, Broadwater G, Klein JP, Antman K, Aisner J, Bitran J et al. High-dose versus standard chemotherapy in metastatic breast cancer: comparison of cancer and leukemia group B trials with data from the autologous blood and marrow transplant registry. J Clin Oncol 2002; 20: 743–750.

    CAS  Article  Google Scholar 

  19. Antman K, Rowlings PA, Vaughan WP, Pelz CJ, Fay JW, Fields KK et al. High-dose chemotherapy with autologous hematopoietic stem-cell support for breast cancer in North America. J Clin Oncol 1997; 15: 1870–1879.

    CAS  Article  Google Scholar 

  20. Rowlings PA, Williams SF, Antman KH, Fields KK, Fay JW, Reed E et al. Factors correlated with progression-free survival after high-dose chemotherapy and hematopoietic stem cell transplantation for metastatic breast cancer. JAMA 1999; 282: 1335–1343.

    CAS  Article  Google Scholar 

  21. Hortobagyi GN . Can we cure limited metastatic breast cancer? J Clin Oncol 2002; 20: 620–623.

    Article  Google Scholar 

  22. Pedrazzoli P, Ferrante P, Kulekci A, Schiavo R, De Giorgi U, Carminati O et al. Autologous hematopoietic stem cell transplantation for breast cancer in Europe: critical evaluation of data from the European Group for Blood and Marrow Transplantation (EBMT) Registry1990–1999. Bone Marrow Transplant 2003; 32: 489–494.

    CAS  Article  Google Scholar 

  23. Nitz UA, Mohrmann S, Fischer J, Lindemann W, Berdel WE, Jackisch C et al. Comparison of rapidly cycled tandem high-dose chemotherapy plus peripheral-blood stem-cell support versus dose-dense conventional chemotherapy for adjuvant treatment of high-risk breast cancer: results of a multicentre Phase III trial. Lancet 2005; 366: 1935–1944.

    CAS  Article  Google Scholar 

  24. Rodenhuis S, Bontenbal M, van Hoesel QG, Smit WM, Nooij MA, Voest EE et al. Efficacy of high-dose alkylating chemotherapy in HER2/neu-negative breast cancer. Ann Oncol 2006; 17: 588–596.

    CAS  Article  Google Scholar 

  25. Lotz JP, Curé H, Janvier M, Asselain B, Morvan F, Legros M et al. High-dose chemotherapy with haematopoietic stem cell transplantation for metastatic breast cancer patients: final results of the French multicentric randomised CMA/PEGASE 04 protocol. Eur J Cancer 2005; 41: 71–80.

    CAS  Article  Google Scholar 

  26. Berry DA, Ueno NT, Johnson MM, Lei X, Caputo J, Rodenhuis S et al. High-dose chemotherapy with autologous stem-cell support as adjuvant therapy in breast cancer: overview of 15 randomized trials. J Clin Oncol 2011; 29: 3214–3223.

    CAS  Article  Google Scholar 

  27. Berry DA, Ueno NT, Johnson MM, Lei X, Caputo J, Smith DA et al. High-dose chemotherapy with autologous hematopoietic stem-cell transplantation in metastatic breast cancer: overview of six randomized trials. J Clin Oncol 2011; 29: 3224–3231.

    Article  Google Scholar 

  28. Miller AB, Hoogstraten B, Staquet M, Winkler A . Reporting results of cancer treatment. Cancer 1981; 47: 207–214a.

    CAS  Article  Google Scholar 

  29. Vandemark RM, Shpall EJ, Affronti ML . Bone metastases from breast cancer: value of bone windows. J Comput Assist Tomography 1992; 16: 608–614.

    CAS  Article  Google Scholar 

  30. Breast International Group (BIG) 1-98 Collaborative Group Thürlimann B, Keshaviah A, Coates AS, Mouridsen H, Mauriac L et al. A comparison of letrozole and tamoxifen in postmenopausal women with early breast cancer. N Engl J Med 2005; 353: 2747–2757.

    Article  Google Scholar 

  31. Pedrazzoli P, Rosti G, Secondino S, Carminati O, Demirer T et al. European Group for Blood and Marrow Transplantation; Solid Tumors Working Party. High-dose chemotherapy with autologous hematopoietic stem cell support for solid tumors in adults. Semin Hematol 2007; 44: 286–295.

    Article  Google Scholar 

  32. Borges VF, Elias AD . The era of high-dose chemotherapy for breast cancer: revisiting a troubled quest. J Clin Oncol 2011; 29: 3205–3206.

    Article  Google Scholar 

  33. Cheng YC, Ueno NT . Is high-dose chemotherapy with autologous hematopoietic stem cell transplantation in breast cancer patients a done deal? Women’s Health 2010; 6: 481–485.

    PubMed  Google Scholar 

  34. Einhorn LH, Williams SD, Chamness A, Brames MJ, Perkins SM, Abonour R . High-dose chemotherapy and stem cell rescue for metastatic germ-cell tumors. N Engl J Med 2007; 357: 340–348.

    CAS  Article  Google Scholar 

  35. Montemurro F, Rondón G, Ueno NT, Munsell M, Gajewski JL, Champlin RE . Factors affecting progression-free survival in hormone-dependent metastatic breast cancer patients receiving high-dose chemotherapy and hematopoietic progenitor cell transplantation: role of maintenance endocrine therapy. Bone Marrow Transplant 2002; 29: 861–866.

    CAS  Article  Google Scholar 

  36. Nieto Y, Nawaz S, Jones RB, Shpall EJ, Cagnoni PJ, McSweeney PA et al. Prognostic model for relapse after high-dose chemotherapy with autologous stem-cell transplantation for stage IV oligometastatic breast cancer. J Clin Oncol 2002; 20: 707–718.

    CAS  Article  Google Scholar 

  37. Kurian S, Qazilbash M, Fay J, Wolff S, Herzig R, Hobbs G et al. Complete response after high-dose chemotherapy and autologous hemopoietic stem cell transplantation in metastatic breast cancer results in survival benefit. Breast J 2006; 12: 531–535.

    CAS  Article  Google Scholar 

  38. Farquhar CM, Marjoribanks J, Lethaby A, Basser R . High dose chemotherapy for poor prognosis breast cancer: systematic review and meta-analysis. Cancer Treat Rev 2007; 33: 325–337.

    CAS  Article  Google Scholar 

  39. Marino P, Roché H, Moatti JP . PEGASE GroupHigh-dose chemotherapy for patients with high-risk breast cancer: a clinical and economic assessment using a quality-adjusted survival analysis. Am J Clin Oncol 2008; 31: 117–124.

    CAS  Article  Google Scholar 

  40. Hortobagyi GN . What is the role of high-dose chemotherapy in the era of targeted therapies? J Clin Oncol 2004; 22: 2263–2266.

    CAS  Article  Google Scholar 

  41. Cheng YC, Rondón G, Sanchez LF, McMannis JD, Couriel DR, de Lima MJ et al. Interleukin-2 and granulocyte-macrophage-colony-stimulating factor immunomodulation with high-dose chemotherapy and autologous hematopoietic stem cell transplantation for patients with metastatic breast cancer. Int J Hematol 2009; 90: 627–634.

    CAS  Article  Google Scholar 

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Acknowledgements

We wish to thank all Italian Centers that gathered all relevant information to locate eligible patients and performed data management: Reggio Calabria (P. Iacopino); University of Genova (R. Gonella, F. Patrone); IRCCS Salvatore Maugeri Foundation, Pavia (GA. Da Prada, A. Lanza); Niguarda Hospital, Milano (S. Siena); San Giovanni Rotondo - Foggia (E. Maiello); University of Pisa; S.Orsola Malpighi Hospital, Bologna (A. Martoni); Perugia (L. Crino’, M.A. Colozza); La Maddalena Hospital, Palermo (F. Porretto); Institute for Cancer Research and Treatment, Candiolo - Torino (A. Capaldi); Noale -Venezia (O. Vinante, M. Bari, G. Azzarello); Humanitas Cancer Center, Rozzano - Milano (A. Santoro, A. Bertuzzi); IRCCS Policlinico S. Matteo Foundation, Pavia (M. Danova); Reggio Emilia (L. Gugliotta, A. Bonini, G. Bisagni); Fatebenefratelli Hospital, Milano (G. Farina, C. Bianchi); Verona (G.L. Cetto, L. Battistelli); Firenze (A. Bosi, S. Guidi); Udine (R. Fanin, F. Patriarca).

Author contributions: Study concepts: Massimo Martino, Massimo Aglietta, Luca Castagna, Giovanni Rosti and Paolo Pedrazzoli. Study design: Massimo Martino, Massimo Aglietta, Luca Castagna, Giovanni Rosti and Paolo Pedrazzoli. Data acquisition: Massimo Martino, Alberto Ballestrero, Alberto Zambelli, Simona Secondino, Michele Aieta, Carmelo Bengala, Anna Marina Liberati, Claudio Zamagni, Maurizio Musso, Massimo Aglietta, Roberta Schiavo, Luca Castagna, Giovanni Rosti and Paolo Pedrazzoli. Quality control of data and algorithms: Massimo Martino, Barbara Bruno and Paolo Pedrazzoli. Data analysis and interpretation: Massimo Martino, Barbara Bruno and Paolo Pedrazzoli. Statistical analysis: Barbara Bruno and Paolo Pedrazzoli. Manuscript preparation: Massimo Martino and Paolo Pedrazzoli. Manuscript editing: Massimo Martino and Paolo Pedrazzoli. Manuscript review: Massimo Martino, Alberto Ballestrero, Alberto Zambelli, Simona Secondino, Michele Aieta, Carmelo Bengala, Anna Maria Liberati, Claudio Zamagni, Maurizio Musso, Massimo Aglietta, Roberta Schiavo, Luca Castana, Giovanni Rosti, Barbara Bruno and Paolo Pedrazzoli.

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Martino, M., Ballestrero, A., Zambelli, A. et al. Long-term survival in patients with metastatic breast cancer receiving intensified chemotherapy and stem cell rescue: data from the Italian registry. Bone Marrow Transplant 48, 414–418 (2013). https://doi.org/10.1038/bmt.2012.149

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Keywords

  • intensified chemotherapy
  • metastatic breast cancer
  • stem cell transplantation
  • toxicity
  • survival

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