Skip to main content
SpringerLink
Log in

Stem Cell Transplantation for Metastatic and High-Risk Nonmetastatic Breast Cancer: A Novel Treatment Approach

  • Chapter
Breast Cancer 2nd edition

Part of the book series: M.D. Anderson Cancer Care Series ((MDCCS))

  • 2485 Accesses

Even after decades of investigation, the role of high-dose chemotherapy (HDC) with autologous hematopoietic stem cell transplantation (AHST) in the treatment of breast cancer remains controversial. In preclinical and clinical studies of breast cancer in the 1980s and 1990s, dose escalation of alkylating agents—such as cyclophosphamide, carboplatin, cisplatin, etoposide, carmustine, and thiotepa—resulted in increased tumor response rates. However, the pace of investigation of HDC with AHST slowed substantially beginning in 1999 because of strong negative perceptions about AHST that arose after the report of medical research fraud in a study by Bezwoda and publication of negative results of randomized clinical trials at the 1999 annual meeting of the American Society of Clinical Oncology. Even though the number of AHST procedures performed for breast cancer has dropped precipitously over the past 6 years, more than 22 phase III clinical trials of HDC with AHST have been conducted and reported to date. The results are conflicting: some results are positive and others are negative. The safety and tolerability of HDC with AHST for breast cancer have improved greatly over the last decade. Improved preparative regimens and advances in supportive care have reduced toxicity, enhanced recovery, and markedly reduced morbidity and mortality. Many regimens can safely be administered on an outpatient basis. Clinical trials of novel uses of stem cell transplantation—e.g., autologous stem cell transplantation in patients who receive targeted therapy directed against bone metastases and circulating tumor cells; allogeneic transplants for enhancement of graft-versus-tumor effects; and use of mesenchymal stem cells as gene delivery systems—are currently being conducted or are being planned at M. D. Anderson Cancer Center. The field of stem cell transplantation continues to be a viable area of research aimed at developing innovative therapies for advanced breast cancer.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 39.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 54.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Basser RL, O’Neill A, Martinelli G, et al. Multicycle dose-intensive chemotherapy for women with high-risk primary breast cancer: results of International Breast Cancer Study Group Trial 15–95. J Clin Oncol 2006;24:370–378.

    Article  PubMed  CAS  Google Scholar 

  • Bergh J, Wiklund T, Erikstein B, et al. Tailored fluorouracil, epirubicin, and cyclophosphamide compared with marrow-supported high-dose chemotherapy as adjuvant treatment for high-risk breast cancer: a randomised trial. Scandinavian Breast Group 9401 study. Lancet 2000;356:1384–1391.

    Article  PubMed  CAS  Google Scholar 

  • Bezwoda WR. Randomized, controlled trial of high dose chemotherapy (HD-CNVp) versus standard dose (CAF) chemotherapy for high risk, surgically-treated, primary breast cancer [abstract]. Proc Am Soc Clin Oncol 1999;18:2a. Abstract 4.

    Google Scholar 

  • Bishop MR, Fowler DH, Marchigiani D, et al. Allogeneic lymphocytes induce tumor regression of advanced metastatic breast cancer. J Clin Oncol 2004;22:3886–3892.

    Article  PubMed  Google Scholar 

  • Brandberg Y, Michelson H, Nilsson B, et al. Quality of life in women with breast cancer during the first year after random assignment to adjuvant treatment with marrow-supported high-dose chemotherapy with cyclophosphamide, thiotepa, and carboplatin or tailored therapy with fluorouracil, epirubicin, and cyclophosphamide: Scandinavian Breast Group Study 9401. J Clin Oncol 2003;21:3659–3664.

    Article  PubMed  CAS  Google Scholar 

  • Bregni M, Dodero A, Peccatori J, et al. Nonmyeloablative conditioning followed by hematopoietic cell allografting and donor lymphocyte infusions for patients with metastatic renal and breast cancer. Blood 2002;99:4234–4236.

    Article  PubMed  CAS  Google Scholar 

  • Carella AM, Cavaliere M, Dejana A, et al. Nonmyeloablative (NMA) chemotherapy with allogeneic hematopoietic transplantation as treatment of malignancy. Bone Marrow Transplant 2000;25(suppl 1):S27.

    Google Scholar 

  • Cheng YC, Ueno NT. [Allogeneic hematopoietic stem cell transplantation for solid tumors in the United States: a review]. Nippon Rinsho 2003;61:1619–1634.

    PubMed  Google Scholar 

  • Coombes RC, Howell A, Emson M, et al. High dose chemotherapy and autologous stem cell transplantation as adjuvant therapy for primary breast cancer patients with four or more lymph nodes involved: long-term results of an international randomised trial. Ann Oncol 2005;16:726–734.

    Article  PubMed  CAS  Google Scholar 

  • Cristofanilli M, Budd GT, Ellis MJ, et al. Circulating tumor cells, disease progression, and survival in metastatic breast cancer. N Engl J Med 2004;351:781–791.

    Article  PubMed  CAS  Google Scholar 

  • Cristofanilli M, Hayes DF, Budd GT, et al. Circulating tumor cells: a novel prognostic factor for newly diagnosed metastatic breast cancer. J Clin Oncol 2005;23:1420–1430.

    Article  PubMed  Google Scholar 

  • Crown J, Perey L, Lind M, et al. Superiority of tandem high-dose chemotherapy (HDC) versus optimized conventionally-dosed chemotherapy (CDC) in patients (pts) with metastatic breast cancer (MBC): the International Randomized Breast Cancer Dose Intensity Study (IBDIS 1) [abstract]. Proc Am Soc Clin Oncol 2003;22:23.

    Google Scholar 

  • Crump M, Gluck S, Stewart D, 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 [abstract]. Proc Am Soc Clin Oncol 2001;20:21a.

    Google Scholar 

  • Ellis M, Hayes DF, Lippman ME. Treatment of metastatic breast cancer. In: Harris J, Lippman M, Morrow M, et al., eds. Diseases of the Breast. 3rd ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2004:1101.

    Google Scholar 

  • Farquhar C, Marjoribanks J, Basser R, et al. High dose chemotherapy and autologous bone marrow or stem cell transplantation versus conventional chemotherapy for women with early poor prognosis breast cancer. Cochrane Database Syst Rev 2005a;3:CD003139.

    PubMed  Google Scholar 

  • Farquhar C, Marjoribanks J, Basser R, et al. High dose chemotherapy and autologous bone marrow or stem cell transplantation versus conventional chemotherapy for women with metastatic breast cancer. Cochrane Database Syst Rev 2005b;3:CD003142.

    PubMed  Google Scholar 

  • Gianni A, Bonadonna G. Five-year results of the randomized clinical trial comparing standard versus high-dose myeloablative chemotherapy in the adjuvant treatment of breast cancer with >3 positive nodes (LN+) [abstract]. Proc Am Soc Clin Oncol 2001;20:21.

    Google Scholar 

  • Greenberg PA, Hortobagyi GN, Smith TL, et al. Long-term follow-up of patients with complete remission following combination chemotherapy for metastatic breast cancer. J Clin Oncol 1996;14:2197–2205.

    PubMed  CAS  Google Scholar 

  • Hortobagyi GN, Buzdar AU, Theriault RL, et al. Randomized trial of high-dose chemotherapy and blood cell autografts for high-risk primary breast carcinoma. J Natl Cancer Inst 2000;92:225–233.

    Article  PubMed  CAS  Google Scholar 

  • Jacobson AF, Shapiro CL, Van den Abbeele AD, et al. Prognostic significance of the number of bone scan abnormalities at the time of initial bone metastatic recurrence in breast carcinoma. Cancer 2001;91:17–24.

    Article  PubMed  CAS  Google Scholar 

  • Leonard RC, Lind M, Twelves C, et al. Conventional adjuvant chemotherapy versus single-cycle, autograft-supported, high-dose, late-intensification chemotherapy in high-risk breast cancer patients: a randomized trial. J Natl Cancer Inst 2004;96:1076–1083.

    PubMed  CAS  Google Scholar 

  • Lotz JP, Cure H, Janvier 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.

    Article  PubMed  CAS  Google Scholar 

  • Montemurro F, Rondón G, Munsell M, et al. Predicting outcome based on Swenerton score in patients with metastatic breast cancer undergoing high-dose chemotherapy and autologous hematopoietic stem cell transplantation: implications for patient selection. Biol Blood Marrow Transplant 2003;9:330–340.

    Article  PubMed  Google Scholar 

  • Nitz UA, Mohrmann S, Fischer J, 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.

    Article  PubMed  CAS  Google Scholar 

  • Peppercorn J, Herndon J 2nd, Kornblith AB, et al. Quality of life among patients with stage II and III breast carcinoma randomized to receive high-dose chemotherapy with autologous bone marrow support or intermediate-dose chemotherapy: results from Cancer and Leukemia Group B 9066. Cancer 2005;104:1580–1589.

    Article  PubMed  Google Scholar 

  • Peters WP, Jones RB, Vredenburgh J, et al. A large, prospective, randomized trial of high-dose combination alkylating agents (CPB) with autologous cellular support (ABMS) as consolidation for patients with metastatic breast cancer achieving complete remission after intensive doxorubicin-based induction therapy (AFM) [abstract]. Proc Am Soc Clin Oncol 1996;15. Abstract 149.

    Google Scholar 

  • Peters WP, Rosner GL, Vredenburgh JJ, et al. Prospective, randomized comparison of high-dose chemotherapy with stem-cell support versus intermediate-dose chemotherapy after surgery and adjuvant chemotherapy in women with high-risk primary breast cancer: a report of CALGB 9082, SWOG 9114, and NCIC MA-13. J Clin Oncol 2005;23:2191–2200.

    Article  PubMed  CAS  Google Scholar 

  • Roche H, Viens P, Biron P, et al. High-dose chemotherapy for breast cancer: the French PEGASE experience. Cancer Control 2003;10:42–47.

    PubMed  Google Scholar 

  • Rodenhuis S, Bontenbal M, Beex LV, et al. High-dose chemotherapy with hematopoietic stem-cell rescue for high-risk breast cancer. N Engl J Med 2003;349:7–16.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Rodenhuis S, Richel DJ, van der Wall E, et al. Randomised trial of high-dose chemotherapy and haemopoietic progenitor-cell support in operable breast cancer with extensive axillary lymph-node involvement. Lancet 1998;352:515–521.

    Article  PubMed  CAS  Google Scholar 

  • Scandinavian Breast Cancer Study Group 9401. Results from a randomized adjuvant breast cancer study with high dose chemotherapy with CTCb supported by autologous bone marrow stem cells versus dose escalated and tailored FEC therapy [abstract]. Proc Am Soc Clin Oncol 1999;18. Abstract 3.

    Google Scholar 

  • Schmid P, Schippinger W, Nitsch T, 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.

    Article  PubMed  CAS  Google Scholar 

  • Stadtmauer EA, O’Neill A, Goldstein LJ, 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.

    Article  PubMed  CAS  Google Scholar 

  • Stadtmauer EA, O’Neill A, Goldstein LJ, et al. Conventional-dose chemotherapy compared with high-dose chemotherapy (HDC) plus autologous stem-cell transplantation (SCT) for metastatic breast cancer: 5-year update of the ‘Philadelphia Trial’ (PBT-1) [abstract]. Proc Am Soc Clin Oncol 2002;21:43a. Abstract 169.

    Google Scholar 

  • Stadtmauer EA, O’Neill A, Goldstein LJ, et al. Phase III randomized trial of high-dose chemotherapy (HDC) and stem cell support (SCT) shows no difference in overall survival or severe toxicity compared to maintenance chemotherapy with cyclophosphamide, methotrexate and 5-fluorouracil (CMF) for women with metastatic breast cancer who are responding to conventional induction chemotherapy: the ‘Philadelphia’ Intergroup Study (PBT-1) [abstract]. Proc Am Soc Clin Oncol 1999;18:2a. Abstract 1.

    Google Scholar 

  • Studeny M, Marini FC, Dembinski JL, et al. Mesenchymal stem cells: potential precursors for tumor stroma and targeted-delivery vehicles for anticancer agents. J Natl Cancer Inst 2004;96:1593–1603.

    Article  PubMed  CAS  Google Scholar 

  • Swenerton KD, Legha SS, Smith T, et al. Prognostic factors in metastatic breast cancer treated with combination chemotherapy. Cancer Res 1979;39:1552–1562.

    PubMed  CAS  Google Scholar 

  • Tallman MS, Gray R, Robert NJ, et al. Conventional adjuvant chemotherapy with or without high-dose chemotherapy and autologous stem-cell transplantation in high-risk breast cancer. N Engl J Med 2003;349:17–26.

    Article  PubMed  CAS  Google Scholar 

  • Tokuda Y, Tajima T, Narabayashi M, et al. Randomized phase III study of high-dose chemotherapy (HDC) with autologous stem cell support as consolidation in high-risk postoperative breast cancer: Japan Clinical Oncology Group (JCOG9208) [abstract]. Proc Am Soc Clin Oncol 2001;38a. Abstract 148.

    Google Scholar 

  • Vredenburgh JJ, Coniglio D, Broadwater G, 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.

    Article  PubMed  CAS  Google Scholar 

  • Weiss RB, Rifkin RM, Stewart FM, et al. High-dose chemotherapy for high-risk primary breast cancer: an on-site review of the Bezwoda study. Lancet 2000;355:999.

    Article  PubMed  CAS  Google Scholar 

  • Yamamoto N, Watanabe T, Katsumata N, et al. Construction and validation of a practical prognostic index for patients with metastatic breast cancer. J Clin Oncol 1998;16:2401–2408.

    PubMed  CAS  Google Scholar 

  • Zander AR, Kröger N, Schmoor C, et al. High-dose chemotherapy with autologous hematopoietic stem-cell support compared with standard-dose chemotherapy in breast cancer patients with 10 or more positive lymph nodes: first results of a randomized trial. J Clin Oncol 2004;22:2273–2283.

    Article  PubMed  CAS  Google Scholar 

Download references

Authors
  1. Naoto T. Ueno
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Michael Andreeff
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Richard E. Champlin
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Department of Surgical Oncology, The University of Texas, M. D. Anderson Cancer Center, Houston, TX 77030-4009, USA

    Kelly K. Hunt MD

  2. Department of Plastic Surgery, The University of Texas, M. D. Anderson Cancer Center, Houston, TX 77030-4009, USA

    Geoffrey L. Robb MD

  3. Department of Radiation Oncology, The University of Texas, M. D. Anderson Cancer Center, Houston, TX 77030-4009, USA

    Eric A. Strom MD

  4. Department of Stem Cell Transplantation and Cellular Therapy Department of Breast Medical Oncology, The University of Texas, M. D. Anderson Cancer Center, Houston, TX 77030-4009, USA

    Naoto T. Ueno MD, PhD

Rights and permissions

Reprints and permissions

Copyright information

© 2008 Springer Science + Business Media, LLC

About this chapter

Cite this chapter

Ueno, N.T., Andreeff, M., Champlin, R.E. (2008). Stem Cell Transplantation for Metastatic and High-Risk Nonmetastatic Breast Cancer: A Novel Treatment Approach. In: Hunt, K.K., Robb, G.L., Strom, E.A., Ueno, N.T. (eds) Breast Cancer 2nd edition. M.D. Anderson Cancer Care Series. Springer, New York, NY. https://doi.org/10.1007/978-0-387-34952-7_13

Download citation

  • DOI: https://doi.org/10.1007/978-0-387-34952-7_13

  • Publisher Name: Springer, New York, NY

  • Print ISBN: 978-0-387-34950-3

  • Online ISBN: 978-0-387-34952-7

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation