Research table: High-dose chemotherapy (bone marrow transplant) for breast cancer treatment

This summary table contains detailed information about research studies. Summary tables are a useful way to look at the science behind many breast cancer guidelines and recommendations. However, to get the most out of the tables, it’s important to understand some key concepts. Learn how to read a research table.

Introduction: Randomized clinical trials in the 1990s studied high-dose chemotherapy (sometimes called bone marrow transplant), which used high doses of drugs to try and kill a large number of cancer cells. The trials showed high-dose chemotherapy was not more effective than standard dose chemotherapy in treating breast cancer [1-2]. In fact, it caused death in about 6% of people [1-2].

High-dose chemotherapy is not used to treat breast cancer.

Study selection criteria: Randomized clinical trials with at least 200 participants and meta-analyses.

Table note: Although each study in this table compared high-dose chemotherapy with standard-dose chemotherapy, the exact drug combinations used varied from study to study.

Study	Study Population (number of participants)	Characteristics of Breast Cancer	Follow-up (years)	Results for Metastatic Breast Cancer	Results for Early and Locally-Advanced Breast Cancers
Randomized clinical trials
Dutch Study Group [3]	885	4 or more positive nodes	20		Breast cancer-specific survival: Better in the high-dose group (52%) vs. the standard dose group (45%). Overall survival: No difference. Treatment-related death: Higher in the high-dose group (2%) vs. the standard dose group (0%).
CALGB, SWOG, NCIC MA-13 [4]	785	10 or more positive nodes	7		Disease-free survival: No difference between the high-dose group and the intermediate-dose groups. Overall survival: No difference between the high-dose group and the intermediate-dose group. Breast cancer recurrence: Among women younger than 50, fewer recurrences among those in the high-dose group vs. the intermediate-dose group. Treatment-related death: Higher in the high-dose group.
Leonard et al. [5]	605	4 or more positive nodes	6		Disease-free survival: No difference between the high-dose group and the low-dose group. Overall survival: No difference between the high-dose group and the low-dose group. Treatment-related death: No difference between the high-dose group and the low-dose group.
Scandinavian Breast Cancer Study Group [6]	525	Risk of recurrence within 5 years is 70% or greater	3		Disease-free survival: Worse in high-dose group. Treatment-related death: None.
Peters et al. [7]	425	Metastatic breast cancer	9	Survival: No difference between the high-dose group and the standard-dose group. Treatment-related death: High (12%) in high-dose group.
West German Study Group [8]	403	9 or more positive nodes	4		Disease-free survival: Better with high-dose chemotherapy (60%) vs. standard therapy (44%). Overall survival: Better with high-dose chemotherapy (75%) vs. standard therapy (70%).
International Breast Cancer Study Group Trial 15-95 [9]	344	10 or more positive nodes OR 4 or more positive nodes and estrogen receptor-negative tumor OR 4 or more positive nodes and tumor size larger than 5 cm	8		Disease-free survival: Better with high-dose chemotherapy (47%) vs. standard therapy (37%). Overall survival: No difference between the high-dose group and the standard therapy group.
Zander et al. [10]	307	10 or more positive nodes	4		Disease-free survival: No difference between the high-dose group and the low-dose group. Overall survival: No difference between the high-dose group and the low-dose group. Treatment-related death: Low (2%) in the high-dose group. Not measured well in the standard treatment arm, so unable to compare. Note: Early results; study is on-going.
International Collaborative Cancer Group [11]	279	4 or more positive nodes	6		Disease-free survival: No difference at 5 years between high-dose and standard dose groups. Overall survival: No difference at 5 years between the high-dose group and the standard dose group. Treatment-related death: Similar number of deaths related to treatment in both groups.
Pooled analyses
Farquhar et al. [12]	5,598 (14 randomized clinical trials)	4 or more positive nodes			Disease-free survival: High-dose group showed benefit at 3 years. No difference found at year 5 or beyond. Overall survival: No difference between the high-dose group and the standard therapy group. Treatment-related death: Higher in the high-dose group. Note: Many studies in this analysis are ongoing.
Farquhar et al. [13]	850 (6 randomized clinical trials)	Metastatic breast cancer		Disease-free survival: Increase in the high-dose group at 1 and 5 years. Overall survival: No difference between the high-dose group and the standard therapy group. Treatment-related death: Higher in the high-dose group.

References

1. 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. Philadelphia Bone Marrow Transplant Group. N Engl J Med. 342: 1069-76, 2000.
2. Crump M, Gluck S, Tu D, et al. Randomized trial of high-dose chemotherapy with autologous peripheral-blood stem-cell support compared with standard-dose chemotherapy in women with metastatic breast cancer: NCIC MA.16. J Clin Oncol. 26(1):37-43, 2008.
3. Steenbruggen TG, Steggink LC, Seynaeve CM, et al. High-dose chemotherapy with hematopoietic stem cell transplant in patients with high-risk breast cancer and 4 or more involved axillary lymph nodes: 20-year follow-up of a phase 3 randomized clinical trial. JAMA Oncol. 6(4):528-534, 2020.
4. Peters WP, Rosner G, Vredenburgh J, 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. 23(10):2191-200, 2005.
5. Leonard RCF, 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. 96(14):1076-83, 2004.
6. The 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 escalated and tailored FEC therapy. Proc Am Soc Clin Oncol. 18:2a(Abstract 3), 1999.
7. Peters WP, Jones RB, Vredenburgh J, et al. A large, prospective, randomized trial of high-dose combination alkylating agent (CPB) with autologous cellular support (ABMS) as consolidation for patients with metastatic breast cancer achieving complete remission after intensive doxorubicin-based induction therapy (AFM). Proc Am Soc Clin Oncol. 15:149a, 1996.
8. Nitz UA, Mohrmann S, Fischer J, et al. for the West German Study Group. 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. 366(9501):1935-44, 2005.
9. Colleoni M, Sun Z, Martinelli G, et al. for the International Breast Cancer Study Group. The effect of endocrine responsiveness on high-risk breast cancer treated with dose-intensive chemotherapy: results of International Breast Cancer Study Group Trial 15-95 after prolonged follow-up. Ann Oncol. 20(8):1344-51, 2009.
10. Zander AR, Kroger 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. 22(12):2273-83, 2004.
11. Coombes RC, Howell A, Emson A on behalf of the International Collaborative Cancer Group (ICCG). 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. 16(5):726-34, 2005.
12. Farquhar C, Marjoribanks J, Lethaby A, Azhar M. High dose chemotherapy and autologous bone marrow or stem cell transplantation versus conventional chemotherapy for women with early poor prognosis breast cancer (Review). Cochrane Database Syst Rev. 5:CD003139, 2016.
13.  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 (Review). The Cochrane Database Syst Rev. 3:CD003142.pub2, 2005.

Updated 08/09/24