Archived Policies - Surgery


Stem-Cell Transplant for Breast Cancer

Number:SUR703.038

Effective Date:04-01-2010

End Date:10-14-2013

Coverage:

This policy is no longer scheduled for routine literature review and update.

Coverage for evaluation of and subsequent single treatment by stem-cell transplant (SCT) (using bone marrow, peripheral blood, or umbilical cord blood as a stem-cell source), derived from a specific donor category, and following a chemotherapy regimen for treatment of breast cancer is identified in the grid below.

Allogeneic

Is considered experimental, investigational and unproven.

Autologous

Is considered experimental, investigational and unproven.

Tandem or Triple Stem-Cell Transplant

Is considered experimental, investigational and unproven. 

Donor Leukocyte Infusion

Is considered experimental, investigational and unproven.

NOTE:  For detailed information on Tandem or Triple Stem-Cell Transplant and Donor Leukocyte Infusion, see Medical Policy SUR703.002, “Stem Cells Reinfusion or Transplantation Following Chemotherapy (General Donor and Recipient Information)”

Description:

Breast cancer comprises several different types that are distinguished mostly by their rate of growth and tendency to spread to other organs.  Staging is based on the degree of spread of the disease.  High-dose therapy has been investigated as a treatment of high-risk stage II, stage III and stage IV disease.  The stages are defined as follows:

  • High-risk stage II - involvement of four or more axillary lymph nodes without metastasis outside the axilla;
  • Stage IIIA - presence of fixed axillary lymph nodes, OR primary tumor larger than 5 centimeters with involvement of axillary lymph nodes;
  • Stage IIIB - presence of brawny induration of the skin overlying the breast due to involvement of lymphatics (also known as inflammatory breast cancer) OR any size primary tumor, having involvement of ipsilateral internal mammary nodes;
  • Stage IV - presence of distant metastases (involvement of the axilla, chest wall, internal mammary nodes or contralateral breast is defined as locoregional disease and does not constitute distant disease).

NOTE:  The stage of disease refers to the stage identified at the time of consideration for high-dose chemotherapy, and not the stage at the time of the original diagnosis of breast cancer.

NOTE:  For additional definitions of evaluations or treatments, and general information other than the specific disease or condition listed in this policy, please see Medical Policy SUR703.002, “Stem Cells Reinfusion or Transplantation Following Chemotherapy (General Donor and Recipient Information).”

Rationale:

High-dose chemotherapy (HDC) followed by hematopoietic stem-cell (HSC) (i.e., blood or marrow) transplant is an effective treatment modality for many patients with certain malignancies and non-malignancies. The rationale of this treatment approach is to provide a very dose-intensive treatment in order to eradicate malignant cells followed by rescue with peripheral blood or bone marrow stem-cells. 

HDC with Autologous Stem-Cell Support

During a 1996 Blue Cross Blue Shield Association (BCBSA) TEC (Technology Evaluation Center) Assessment, the focus was on HDC with autologous stem-cell support (AuSCS) to treat metastatic (i.e., Stage IV) breast cancer, while the 1998 Assessment focused on HDC with AuSCS for adjuvant therapy of high-risk primary (i.e., Stage II/III) breast cancer.  Research found from 1999 included results presented at the annual meeting of the American Society of Clinical Oncology (ASCO) and published as abstracts.

Conclusions of the 1996 TEC Assessment were as follows:

Twelve studies were reviewed with a total of 459 patients. These included:

  • a trial from South Africa (published in 1995 and discredited in 2001 because of scientific misconduct) that randomized patients not previously treated for metastatic breast cancer to HDC/AuSCS or to conventional-dose therapy;
  • a crossover trial (still published only as an abstract) that randomized complete responders after induction chemotherapy to immediate consolidation with HDC/AuSCS or to HDC/AuSCS delayed until relapse; and
  • 10 uncontrolled series.

The Assessment also reviewed registry data showing marked decreases in transplant-related mortality between 1992 and 1994 that were attributable to improvements in supportive care and the shift from bone marrow to mobilized peripheral blood progenitors as the source of hematopoietic stem cells.  The (now discredited) South African trial reported longer survival for patients in the HDC arm (median 1.7 years), although survival in the conventional-dose arm (median 0.9 years) was shorter than reported with conventional regimens used most commonly in the United States.  The crossover trial reported longer disease-free survival (median, 0.85 vs. 0.32 years) but shorter overall survival (median, 1.7 years vs. 3.2 years) in the immediate than in the delayed HDC arm.  When combined with results of uncontrolled studies, the balance of evidence available in 1996 suggested that HDC/AuSCS yielded survival durations at least equivalent to those after conventional-dose therapy.  Although acute treatment-related morbidity was more severe, the duration of therapy was much shorter with HDC/AuSCS.  Therefore, the BCBSA Medical Advisory Panel (MAP) concluded HDC/AuSCS met the TEC criteria for patients with previously untreated, responsive, or relapsed metastatic breast cancer but not for those with metastatic disease that is refractory to chemotherapy.  Since available evidence was insufficient to determine whether outcomes of either treatment alternative were superior, patients were encouraged to seek this treatment in the context of continued clinical trials.

Conclusions of the 1998 TEC Assessment were as follows:

Adjuvant Therapy for High-Risk Primary (Stage II/III) Breast Cancer:

Surgery excises all evident disease for most patients with Stage II/III breast cancer (except those with inflammatory breast cancer).  Adjuvant (i.e., postoperative) radiation therapy reduces relapse and improves survival.  For those at high risk, adjuvant chemotherapy further reduces recurrence and metastasis and also extends survival.  Evidence reviewed for this Assessment, comparing HDC/AuSCS with conventional-dose chemotherapy for adjuvant treatment, included:

  • two small randomized trials (39–41 patients per arm), a case-control study (60 patients per group), and six uncontrolled series (combined n=302) of patients with 10 or more positive lymph nodes;
  • two uncontrolled series (combined n=116) of patients with 4–9 positive nodes; and
  • three uncontrolled series (combined n=86) of patients with non-metastatic inflammatory breast cancer.

For patients with 10 or more positive nodes, the two randomized trials (one published as an abstract) reported 60%–70% survival at five years, with no statistically significant differences between treatment arms.  The case-control study and the uncontrolled series suggested longer duration of overall and disease-free survival than in previous studies of conventional-dose adjuvant therapy in patients with 10 or more positive nodes.  However, the case-control study only matched for a subset of known risk factors.  Also, patients treated with HDC/AuSCS in uncontrolled series were generally younger and had better performance status than those given conventional-dose adjuvant therapy.  Thus, the analysis could not exclude contributions of patient selection bias to outcome differences.  Consequently, the MAP found available evidence insufficient to permit conclusions, and HDC/AuSCS did not meet the TEC criteria for adjuvant therapy of Stage II/III breast cancer in patients with 10 or more positive nodes.  HDC/AuSCS also failed the TEC criteria for patients with four to nine positive nodes or those with inflammatory breast cancer, since the lack of controlled studies, small sample sizes, and inadequate follow-up did not permit conclusions.

In May 1999 at an ASCO (American Society of Clinical Oncology) annual meeting, highly publicized results were presented from randomized trials of HDC for adjuvant therapy of high-risk primary breast cancer (three studies) or for metastatic breast cancer (two studies).  These preliminary results did not change the conclusions of the 1996 and 1998 TEC Assessments. Results of these studies are summarized as follows:

The PBT-1 trial randomized patients with a complete or partial response to induction therapy for previously untreated metastatic breast cancer to HDC/AuSCS (n=101) or to conventional-dose maintenance chemotherapy (n=83) for up to two years.  Median survival (24 vs. 26 months) and overall survival at three years (32% vs. 38%) did not differ between arms.  There also were no statistically significant differences between arms in time to progression or progression-free survival at three years. While treatment duration was substantially shorter for those randomized to HDC/AuSCS, acute morbidity was markedly more severe than after conventional-dose maintenance.

PEGASE-04, a small (total n=61) French randomized trial for patients with chemotherapy-sensitive metastatic breast cancer, reported a significantly longer median duration of progression-free survival for those in the HDC arm (27 vs.16 months; p=0.04).  The median duration of overall survival also was longer in the HDC arm, although this difference was not statistically significant (36 vs.16 months; p=0.08).

Preliminary results of a CALGB/Intergroup trial (ASCO abstract No. 2) for patients with 10 or more positive nodes did not show statistically significant survival differences between the HDC and conventional chemotherapy arms.  However, the data was not yet sufficiently mature, since the designated endpoint of the trial required a 5-year follow-up, and this interim analysis was based on a median follow-up of 37 months.  A Scandinavian Breast Cancer Study Group trial on patients with eight or more positive nodes also reported no significant difference in event-free or overall survival between the HDC and conventional arms at a median follow-up of 24 months. However, the control arm in this study received an individualized and dose-escalated regimen with higher cumulative doses than those in the HDC arm.  This “tailored” regimen increased the combined incidence of secondary leukemia and myelodysplasia.  A South African study for patients with 10 or more positive nodes was unique in reporting improved median relapse-free survival in the HDC arm.  However, this trial also was unique since all patients were treated with HDC immediately without initial conventional-dose adjuvant chemotherapy. [Note also that this trial was discredited in 2000 based on evidence of scientific misconduct.]  All three trials reported higher incidences of severe non-lethal toxicity in the HDC arms. Also, no data was reported from ongoing randomized trials for patients with 4-9 positive lymph nodes.

Of the two trials for metastatic breast cancer presented at ASCO in 1999, only the PBT-1 trial was published as a peer-reviewed journal article.  Published results confirmed those reported at the meeting.  However, some reviewers criticized this trial since few partial responses were converted to complete responses in the high-dose arm, and since only a minority of those enrolled was subsequently randomized.  Of 553 patients enrolled and given initial induction therapy, only 310 achieved a partial (n=252) or complete (n=58) response, and only 199 were randomized.  Of 72 partial responders assigned to the HDC arm after initial induction therapy, only five (7%) were converted to complete responses.

Of the three trials for adjuvant therapy of high-risk primary breast cancer presented at the 1999 ASCO meeting, only the Scandinavian study was published as a peer-reviewed article.  Published results confirmed those reported at the meeting.  Although an update was presented at the 2001 ASCO meeting, the CALGB (Cancer and Leukemia Group B)/Intergroup trial had not yet published final outcomes.  A small pilot trial from the Netherlands with 81 patients randomized to HDC/AuSCS or conventional-dose therapy and a median of seven years’ follow-up reported no differences in overall or disease-free survival at five years.  Several larger randomized trials, including the study sponsored by the National Cancer Institute (NCI) for patients with four to nine positive nodes, had completed accrual and were continuing to follow up patients.  Although several had reported interim results as meeting presentations, reviewers generally agreed that definitive conclusions required final analyses and peer-reviewed publications.

Two additional trials were reported at ASCO meetings in 2000 and 2001, but were available only as abstracts.  A small crossover study, limited to women whose disease did not progress after induction therapy for bone-only metastases, reported modest improvement in progression-free survival (but no effect on overall survival) from immediate compared with delayed HDC/AuSCS. A larger Canadian randomized trial without crossover reported interim results at 19 months median follow-up.  In this analysis, progression-free survival was longer (but overall survival was equivalent) for those randomized to HDC/AuSCS.  However, grade three and four toxicities were more common after HDC/AuSCS.  Definitive conclusions required longer follow-up and analysis of final outcomes.

During 2003 and 2004, four trials reported final outcomes analyses from randomized comparisons of HDC/AuSCS versus conventional doses for adjuvant therapy of high-risk non-metastatic breast cancer.  Evidence from these trials did not support the conclusion that HDC/AuSCS improved outcomes when compared with conventional-dose adjuvant therapy.  An editorial that accompanied one report briefly reviewed and commented on factors contributing to diffusion of HDC/AuSCS into routine practice without adequate testing in randomized clinical trials.  The author also pointed out that of 10 adjuvant therapy trials comparing high-dose to conventional-dose regimens (pooled n=4,521), none reported a statistically significant benefit in overall survival for the HDC/AuSCS arm, and only one reported improved disease-free survival. However, eight trials lacked adequate statistical power, likely from two factors: slow accrual leading to early closure, and overly optimistic expectations on the magnitude of benefit.  The editorialist also suggested that meta-analysis of these trial results might be useful to test whether further studies are warranted for any subgroup (e.g., younger patients with tumors that are high grade or lack hormone receptors).  He noted that meta-analysis has been useful to estimate the benefit from adjuvant chemotherapy with various conventional-dose regimens.  The editorial concluded that the major lesson from the past decade’s work on HDC/AuSCS “…is that good ideas and good hypotheses are insufficient justification for routinely adopting a therapeutic strategy…” without adequate testing in rigorous, adequately powered, comparative trials.  A recent review also concluded that HDC/AuSCS does not improve relapse-free or overall survival of women with high-risk breast cancer.

A Cochrane systematic review and meta-analysis published in July 2005 pooled data from six randomized controlled trials (RCTs) on metastatic breast cancer reported through November 2004 (N=438 randomized to HDC/AuSCS, 412 to conventional dose therapy).  The relative risk for treatment-related mortality was significantly higher in the arm randomized to HDC/AuSCS (15 vs. 2 deaths; RR=4.07; 95% CI: 1.39, 11.88).  Treatment-related morbidity also was more severe among those randomized to HDC/AuSCS.  Overall survival did not differ significantly between groups at one, three, or five years after treatment.  Statistically significant differences in event-free survival at one year (RR=1.76; 95% CI: 1.40, 2.21) and five years (RR=2.84; 95% CI: 1.07, 7.50) favored the HDC/AuSCS arms.  Only one of the six included trials had followed up all patients for at least five years.  Reviewers recommended further follow-up for patients randomized in the other five trials.  They also concluded that, in the interim, patients with metastatic breast cancer should not receive HDC/AuSCS outside of a clinical trial, since available data showed greater treatment-related mortality and toxicity without improved overall survival.

A second Cochrane systematic review and meta-analysis, also published in July 2005, included data from 13 RCTs on patients with high-risk (poor prognosis) early breast cancer (N=2,535 randomized to HDC/AuSCS, 2,529 to conventional dose therapy).  Treatment-related mortality was significantly greater among those randomized to HDC/AuSCS (65 vs. 4 deaths; RR=8.58; 95% CI: 4.13, 17.80).  Treatment-related morbidity also was more common and more severe in the high-dose arms.  There were no significant differences between arms in overall survival rates at any time after treatment.  Event-free survival was significantly greater in the HDC/AuSCS group at three years (RR=1.12; 95% CI: 1.06, 1.19) and four years (RR=1.30; 95% CI: 1.16, 1.45) after treatment.  However, the two groups did not differ significantly with respect to event-free survival at five and six years after treatment.  There was also no statistically significant difference between groups in the incidence of secondary malignancies at five to seven years of follow-up.  Quality of life scores were significantly worse in the HDC/AuSCS arms than in controls soon after treatment, but differences were no longer statistically significant by one year. Reviewers concluded available data were insufficient to support routine use of HDC/AuSCS for patients with poor-prognosis early breast cancer.

HDC with Allogeneic Stem-Cell Support

There are inadequate studies to evaluate outcomes of HDC/AlloSCS (allogeneic stem-cell support) in the treatment of breast cancer. Although several uncontrolled studies subsequently were published on use of non-myeloablative conditioning regimens for allotransplants, data still were lacking from controlled trials. Furthermore, evidence is scant for an immunologic graft-versus-tumor effect after allotransplants for breast cancer.  Moreover, a 1999 TEC Assessment found inadequate data regarding the use of HDC/AlloSCS as salvage therapy after a failed prior course of HDC/AuSCS.

At a median follow-up of 12 years, researchers continued to demonstrate no recurrence-free survival or overall survival advantage for patients with high-risk primary breast cancer treated with HDCT after standard dose chemotherapy.  Coombes and colleagues reported no benefit from replacing three cycles of conventional chemotherapy with a high-dose regimen and stem-cell rescue given as adjuvant therapy.  Kroger reported that tandem high-dose therapy (HDT) cannot be recommended for patients with chemotherapy-sensitive metastatic breast cancer because of a trend for shorter overall survival and higher toxicity compared with single HDT in spite of a trend of improved progression-free survival.  

Tandem or Triple Stem-Cell Transplant

Tandem or Triple Stem-Cell Transplant for breast cancer is considered experimental, investigational, and unproven due to lack of adequate evidence of safety and effectiveness documented in published, peer-reviewed medical literature.  Several uncontrolled pilot or Phase II trials reported results after two or three sequential cycles of HDC/AuSCS for patients with metastatic high-risk operable or inflammatory breast cancer.  However, data were unavailable from randomized studies that directly compared outcomes of tandem transplants with those of either single transplants or conventional-dose regimens.

Donor Leukocyte Infusion (DLI)

Donor Leukocyte Infusion (DLI) for breast cancer is considered experimental, investigational, and unproven due to lack of adequate evidence of safety and effectiveness documented in published, peer-reviewed medical literature.

Contract:

Each benefit plan, summary plan description or contract defines which services are covered, which services are excluded, and which services are subject to dollar caps or other limitations, conditions or exclusions. Members and their providers have the responsibility for consulting the member's benefit plan, summary plan description or contract to determine if there are any exclusions or other benefit limitations applicable to this service or supply. If there is a discrepancy between a Medical Policy and a member's benefit plan, summary plan description or contract, the benefit plan, summary plan description or contract will govern.

Coding:

None  

CODING:

Disclaimer for coding information on Medical Policies          

Procedure and diagnosis codes on Medical Policy documents are included only as a general reference tool for each policy.  They may not be all-inclusive.           

The presence or absence of procedure, service, supply, device or diagnosis codes in a Medical Policy document has no relevance for determination of benefit coverage for members or reimbursement for providers.  Only the written coverage position in a medical policy should be used for such determinations.           

Benefit coverage determinations based on written Medical Policy coverage positions must include review of the member’s benefit contract or Summary Plan Description (SPD) for defined coverage vs. non-coverage, benefit exclusions, and benefit limitations such as dollar or duration caps. 

CPT/HCPCS/ICD-9/ICD-10 Codes

The following codes may be applicable to this Medical policy and may not be all inclusive.

CPT Codes

36511, 38204, 38205, 38206, 38207, 38208, 38209, 38210, 38211, 38212, 38213, 38214, 38215, 38220, 38221, 38230, 38232, 38240, 38241, 38242, 38243, 81265, 81266, 81267, 81268, 81370, 81371, 81372, 81373, 81374, 81375, 81376, 81377, 81378, 81379, 81380, 81381, 81382, 81383, 86805, 86806, 86807, 86808, 86812, 86813, 86816, 86817, 86821, 86822, 86825, 86826, 86849, 86950, 86985, 88240, 88241

HCPCS Codes

S2140, S2142, S2150

ICD-9 Diagnosis Codes

174, 174.9, 233.0

ICD-9 Procedure Codes

41.00, 41.01, 41.02, 41.03, 41.04, 41.05, 41.06, 41.07, 41.08, 41.09, 41.91, 99.25, 99.74, 99.79

ICD-10 Diagnosis Codes

 

ICD-10 Procedure Codes

 


Medicare Coverage:

The information contained in this section is for informational purposes only.  HCSC makes no representation as to the accuracy of this information.  It is not to be used for claims adjudication for HCSC Plans.

The Centers for Medicare and Medicaid Services (CMS) does have a national Medicare coverage position.

A national coverage position for Medicare may have been developed or changed since this medical policy document was written.  See Medicare's National Coverage at <http://www.cms.hhs.gov>.

References:

High-Dose Chemotherapy with Autologous Stem-Cell Support in the Treatment of Metastatic Breast Cancer. Chicago, Illinois: Blue Cross Blue Shield Association – Technology Evaluation Center Assessment Program (1996 June) 11(3):1-27.

High-Dose Chemotherapy with Autologous Stem-Cell Support in the Treatment of High-Risk,

Primary Breast Cancer. Chicago, Illinois: Blue Cross Blue Shield Association - Technology Evaluation Center Assessment Program (1999 February) 13(24):1-36.

Stadtmauer, E.A., O’Neill, L.J., et al. Phase III randomized trial of high-dose chemotherapy and stem cell support shows no difference in overall survival or severe toxicity compared to maintenance chemotherapy with cyclophosphamide, methotrexate, and 5-fluorouracil for women with metastatic breast cancer who are responding to conventional induction chemotherapy: The Philadelphia Intergroup Study (PBT-1). Annual Meeting American Society of Clinical Oncology. (1999) 18:1a (abstract no. 1).

Lotz, J.P., Cure, H., et al. High dose chemotherapy with hematopoietic stem cells transplantation for metastatic breast cancer. Results of the French protocol PEGASE-04.  Annual Meeting American Society of Clinical Oncology (1999) 18:43a (abstract no. 161).

Peters, W.P., Rosner, G., et al. A prospective randomized comparison of two doses of combination alkylating agents are consolidation after CAF in high risk primary breast cancer involving ten or more axillary lymph nodes: Preliminary results of CALGB (Cancer and Leukemia Group B) 9082/SWOG9114/NCIC MA-13. Annual Meeting American Society of Clinical Oncology (1999) 18:1a (abstract no. 2).

The Scandinavian Breast Cancer Study Group 9401. Results from a randomized adjuvant breast cancer study with high dose chemotherapy with CTC, supported by autologous bone marrow stem cells versus dose escalated and tailored FEC therapy. Annual Meeting American Society of Clinical Oncology (1999) 18:2a (abstract no. 3).

Bezwoda, W.R. Randomized controlled trial of high dose chemotherapy versus standard dose chemotherapy for high risk, surgically treated primary breast cancer.  Annual Meeting American Society of Clinical Oncology (1999) 18:2a (abstract no. 4).

Farquhar, C., Marjoribanks, J., 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 Systematic Review (2005); (3):CD003139.

Salvage HDC/AlloSCS for Relapse following HDC/AuSCS for Non-Lymphoid Solid Tumors.  Chicago, Illinois: Blue Cross Blue Shield Association – Technology Evaluation Center Assessment Program (1999 July) 14(11):1-9.

Weiss, R.B., Rifkin, R.M., et al. High-dose chemotherapy for high-risk primary breast cancer: an on-site review of the Bezwoda study. Lancet (2000); 355(9208):999-1003.

Stadtmauer, E.A., O'Neill, A., 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. New England Journal of Medicine (2000) 342(15):1069-76.

Madan, B., Broadwater, G., et al. Improved survival with consolidation high-dose cyclophosphamide, cisplatin and carmustine (HD-CPB) compared with observation in women with metastatic breast cancer (MBC) and only bone metastases treated with induction Adriamycin, 5-fluorouracil and methotrexate (AFM): a phase III prospective randomized comparative trial. Annual Meeting American Society of Clinical Oncology (2000) 19:48a (abstract no. 184).

Bergh, J., Wiklund, T., et al. Tailored fluorouracil, epirubicin, and cyclophosphamide compared with marrow-supported high-dose chemotherapy as adjuvant treatment for high-risk breast cancer: a randomized trial. Scandinavian Breast Group 9401 study. Lancet (2000) 356(9239):1384-91.

Macquart-Moulin, G., Viens, P., et al. High-dose sequential chemotherapy with recombinant granulocyte colony-stimulating factor and repeated stem-cell support for inflammatory breast cancer patients: does impact on quality of life jeopardize feasibility and acceptability of treatment? Journal of Clinical Oncology (2000) 18(4):754-64.

Baynes, R.D., Dansey, R.D., et al. High-dose chemotherapy and hematopoietic stem cell transplantation for breast cancer: past or future? Seminars in Oncology (2001) 28(4):377-88.

Pedrazzoli, P., Siena, S. Clinical results in 2001 show high dose therapy and hematopoietic progenitor cell transplantation as a therapeutic option for breast cancer. Haematologica (2001) 86(9):900-7.

Antman KH. A critique of the eleven randomized trials of high-dose chemotherapy for breast cancer. European Journal of Cancer (2001) 37(2):173-9.

Weiss, R.B., Gill, G.G., et al.  An on-site audit of the South African trial of high-dose chemotherapy for metastatic breast cancer and associated publications. Journal of Clinical Oncology (2001) 19(11):2771-7.

Crump, M., Gluck, S., 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. Annual Meeting American Society of Clinical Oncology (2001) 20:21a (abstract no. 82).

Peters, W.P., Rosner, G., et al. Updated results of a prospective, randomized comparison of two doses of combination alkylating agents (AA) as consolidation after CAF in high-risk primary breast cancer involving ten or more axillary lymph nodes (LN): CALGB 9082/SWOG 9114/NCIC Ma-13. Annual Meeting American Society of Clinical Oncology (2001) 20:21a (abstract no. 81).

Elias, A.D., Richardson, P., et al. A short course of induction chemotherapy followed by two cycles of high-dose chemotherapy with stem cell rescue for chemotherapy naive metastatic breast cancer. Bone Marrow Transplant (2001) 27(3):269-78.

Elias, A.D., Richardson, P., et al. A short course of induction chemotherapy followed by two cycles of high-dose chemotherapy with stem cell rescue for chemotherapy naive metastatic breast cancer: sequential phase I/II studies. Bone Marrow Transplant (2001) 28(5):447-54.

Pecora, A.L., Lazarus, H.M., et al. Effect of induction chemotherapy and tandem cycles of high-dose chemotherapy on outcomes in autologous stem cell transplant for metastatic breast cancer. Bone Marrow Transplant (2001) 27(12):1245-53.

Schrama, J.G., Baars, J.W., et al. Phase II study of a multi-course high-dose chemotherapy regimen incorporating cyclophosphamide, thiotepa, and carboplatin in stage IV breast cancer. Bone Marrow Transplant (2001) 28(2):173-80.

Somlo, G., Chow, W., et al. Tandem-cycle high-dose melphalan and cisplatin with peripheral blood progenitor cell support in patients with breast cancer and other malignancies. Biology of Blood and Marrow Transplantation (2001) 7(5):284-93.

Dazzi, C., Cariello, A., et al. Neoadjuvant high dose chemotherapy plus peripheral blood progenitor cells in inflammatory breast cancer: a multicenter phase II pilot study. Haematologica (2001) 86(5):523-9.

Schrama, J.G., Faneyte, I.F., et al. Randomized trial of high-dose chemotherapy and hematopoietic progenitor-cell support in operable breast cancer with extensive lymph node involvement: final analysis with 7 years of follow-up. Annals of Oncology (2002); 13(5):689-98.

Dicato, M. High-dose chemotherapy in breast cancer: where are we now? Seminars in Oncology (2002); 29(3 suppl 8):16-20.

Bregni, M., Dodero, A., et al. Nonmyeloablative conditioning followed by hematopoietic cell allografting and donor lymphocyte infusions for patients with metastatic renal and breast cancer. Blood (2002) 99(11):4234-6.

Carella, A.M., Beltrami, G., et al. Combined use of autografting and non-myeloablative allografting for the treatment of hematologic malignancies and metastatic breast cancer. Cancer Treatment and Research (2002) 110:101-12.

Gerrero, R.M., Stein, S., et al. High-dose chemotherapy and stem cell support for breast cancer: where are we now? Drugs Aging (2002) 19(7):475-85.

Schmid, P., Possinger, K. High-dose chemotherapy in high-risk primary breast cancer. Onkologie (2002) 25(2):112-20.

Rodenhuis, S., Bontenbal, M., et al. High-dose chemotherapy with hematopoietic stem-cell rescue for high-risk breast cancer. New England Journal of Medicine (2003) 349(1):7-16.

Tallman, M.S., Gray, R., et al. Conventional adjuvant chemotherapy with or without high-dose chemotherapy and autologous stem-cell transplantation in high-risk breast cancer. New England Journal of Medicine (2003) 349(1):17-26.

Sayer, H.G., Schilling, K., et al. Double high-dose chemotherapy with adriamycin, paclitaxel, cyclophosphamide, and thiotepa followed by autologous peripheral blood stem cell transplantation in women with metastatic breast cancer. Journal of Cancer Research and Clinical Oncology (2003) 129(6):361-6.

Leonard, R.C., Lind, M., et al. Conventional adjuvant chemotherapy versus single-cycle, autograft-supported, high-dose, late-intensification chemotherapy in high-risk breast cancer patients: a randomized trial. Journal of the National Cancer Institute (2004) 96(14):1076-83.

Zander, A.R., Kroger, N., 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. Journal of Clinical Oncology (2004) 22(12):2273-83.

Hortobagyi, G.N. What is the role of high-dose chemotherapy in the era of targeted therapies? Journal of Clinical Oncology (2004) 22(12):2263-6.

Carlson, R.W., Wheatley, K. High-dose chemotherapy and stem cell transplantation does not improve relapse-free or overall survival in women with high-risk breast cancer. Cancer Treatment Reviews (2004) 30(1):131-7.

Donor Leukocyte Infusion for Hematologic Malignancies that Relapse after Allogeneic Stem Cell Transplant. BCBSA Medical Policy Reference Manual (2005 September) Medicine: 2.03.03.

Farquhar, C., Marjoribanks, J., et al. High dose chemotherapy and autologous bone marrow or stem cell transplantation versus conventional chemotherapy for women with metastatic breast cancer. Cochrane Database Systematic Reviews (2005) (3):CD003142.

Coombes, R.C., Howell, A., 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 randomized trial. Annals of Oncology (2005) 16(5):726-34.

Hanrahan, E.O., Broglio, K., et al. Randomized trial of high-dose chemotherapy and autologous hematopoietic stem cell support for high-risk primary breast carcinoma: follow-up at 12 years. Cancer (2006) 106(11):2327-36.

Kroger, N., Frick, M., et al. Randomized trial of single compared with tandem high-dose chemotherapy followed by autologous stem-cell transplantation in patient with chemotherapy-sensitive metastatic breast cancer. Journal of Clinical Oncology (2006); 24(24):1919-26.

High-Dose Chemotherapy with Hematopoietic Stem-Cell Support for Breast Cancer. Chicago, Illinois: Blue Cross Blue Shield Association Medical Policy Reference Manual (2007 December) Therapy 8.01.27.

Policy History:

4/1/2010          New medical document originating from: SUR703.017, Peripheral/Bone Marrow Stem Cell Transplantation (PSCT/BMT) for Non-Malignancies; SUR703.018, Peripheral/Bone Marrow Stem Cell Transplantation (PSCT/BMT) for Malignancies; SUR703.022, Cord Blood as a Source of Stem Cells (CBSC); SUR703.023, Donor Leukocyte Infusion (DLI); and SUR703.024, Tandem/Triple High-Dose Chemoradiotherapy with Stem Cell Support for Malignancies.  Stem cell transplant remains experimental, investigational and unproved when used to treat breast cancer.

[NOTE: A link to the medical policies with the following titles can be found at the end of the medical policy SUR703.002, Stem-Cell Reinfusion or Transplantation Following Chemotherapy (General Donor and Recipient Information):

  • Peripheral/Bone Marrow Stem Cell Transplantation (PSCT/BMT) for Non-Malignancies;
  • Peripheral/Bone Marrow Stem Cell Transplantation (PSCT/BMT) for Malignancies;
  • Cord Blood as a Source of Stem Cells;
  • Donor Leukocyte Infusion (DLI); and
  • Tandem/Triple High-Dose Chemoradiotherapy with Stem Cell Support for Malignancies.

Archived Document(s):

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