Skip to main content

Advertisement

SpringerLink
Log in

Predictors of reduced dose intensity in patients with early-stage breast cancer receiving adjuvant chemotherapy

  • Clinical Trial
  • Published:
Breast Cancer Research and Treatment Aims and scope Submit manuscript

Abstract

Background

This retrospective study was undertaken to define risk factors for reductions in dose intensity of adjuvant chemotherapy in women with early stage breast cancer (ESBC).

Methods

A nationwide survey of 190 community oncology practices was conducted between 1998 and 2002 with data collected retrospectively on 3,707 patients treated with adjuvant chemotherapy for ESBC. End points included reductions in dose intensity, delivered relative dose intensity (RDI) <85%, and the incidence of chemotherapy dose delays ≥7 days and dose reduction ≥15%. Demographic and clinical characteristics, incidence of febrile neutropenia (FN), and patterns of use of granulocyte colony-stimulating factor (G-CSF) were also assessed.

Results

Average RDI for all regimens was 88%, with 30% of patients receiving <85% of standard for their regimen. Seventeen percent of the reduction in average RDI was planned from the start of therapy, and 13% was unplanned. In univariate analysis, significant predictors of reduced RDI were: age ≥65 years (41%, P < 0.001), body surface area (BSA) >2 m2 (37%, P < 0.001), negative lymph nodes (33%, P < 0.001), FN (36%, P = 0.013), and comorbidities (40%, P = 0.013), particularly renal disease (86%, P = 0.004). Dose reduction was less with prophylactic G-CSF (24%, P < 0.001). In multivariate analysis, significant independent predictors of reduced RDI included: advanced age, greater BSA, comorbidities, anthracycline-based regimens, a 28-day schedule and FN, while primary G-CSF prophylaxis was associated with a significant reduction in risk.

Conclusion

A significant proportion of patients with potentially curable ESBC continue to experience planned and unplanned reductions in RDI.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Early Breast Cancer Trialists’ Collaborative Group (EBCTCG) (2005) Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomized trials. Lancet 365:1687–1717

    Article  CAS  Google Scholar 

  2. Bonadonna G, Valagussa P, Moliterni A et al (1995) Adjuvant cyclophosphamide, methotrexate, and fluorouracil in node-positive breast cancer: the results of 20 years of follow-up. N Engl J Med 332:901–906

    Article  PubMed  CAS  Google Scholar 

  3. Wood WC, Budman DR, Korzun AH et al (1994) Dose and dose intensity of adjuvant chemotherapy for stage II, node-positive breast carcinoma. N Engl J Med 330:1253–1259

    Article  PubMed  CAS  Google Scholar 

  4. Budman DR, Berry DA, Cirrincione CT et al (1998) Dose and dose intensity as determinants of outcome in the adjuvant treatment of breast cancer. J Natl Cancer Inst 90:1205–1211

    Article  PubMed  CAS  Google Scholar 

  5. Piccart MJ, Biganzoli L, Di Leo A (2000) The impact of chemotherapy dose density and dose intensity on breast cancer outcome: what have we learned? Eur J Cancer 36(Suppl 1):S4–S10

    Article  PubMed  CAS  Google Scholar 

  6. Chang J (2000) Chemotherapy dose reduction and delay in clinical practice: evaluating the risk to patient outcome in adjuvant chemotherapy for breast cancer. Eur J Cancer 36(Suppl 1):S11–S14

    Article  PubMed  CAS  Google Scholar 

  7. Adjuvant therapy for breast cancer (2000) NIH Consensus Statement 17:1–35

    Google Scholar 

  8. Citron ML, Berry DA, Cirrincione C et al (2003) Randomized trial of dose-dense versus conventionally scheduled and sequential versus concurrent combination chemotherapy as postoperative adjuvant treatment of node-positive primary breast cancer: first report of Intergroup trial C9741/Cancer and Leukemia Group B trial 9741. J Clin Oncol 21:1431–1439

    Article  PubMed  CAS  Google Scholar 

  9. Lyman GH, Dale DC, Crawford J (2003) Incidence and predictors of low dose-intensity in adjuvant breast cancer chemotherapy: a nationwide study of community practices. J␣Clin Oncol 21:4524–4531

    Article  PubMed  Google Scholar 

  10. Lyman GH, Dale DC, Friedberg J et al (2004) Incidence and predictors of low chemotherapy dose-intensity in aggressive non-Hodgkin’s lymphoma: a nationwide study. J Clin Oncol 22:4302–4311

    Article  PubMed  CAS  Google Scholar 

  11. Dale DC, McCarter GC, Crawford J et al (2003) Myelotoxicity and dose intensity of chemotherapy: reporting practices from randomized clinical trials. JNCCN 1:440–454

    Google Scholar 

  12. Harlan LC, Clegg LX, Abrams J et al (2006) Community-based use of chemotherapy and hormonal therapy for early-stage breast cancer: 1987–2000. J Clin Oncol 24:872–877

    Article  PubMed  CAS  Google Scholar 

  13. Mayers C, Panzarella T, Tannock IF (2001) Analysis of the prognostic effects of inclusion in a clinical trial and of myelosuppression on survival after adjuvant chemotherapy for breast carcinoma. Cancer 91:2246–2257

    Article  PubMed  CAS  Google Scholar 

  14. Cameron DA, Massie C, Kerr G et al (2003) Moderate neutropenia with adjuvant CMF confers improved survival in early breast cancer. Br J Cancer 89:1837–1842

    Article  PubMed  CAS  Google Scholar 

  15. Saarto T, Blomqvist C, Rissanen P et al (1997) Haematological toxicity: a marker of adjuvant chemotherapy efficacy in stage II and III breast cancer. Br J Cancer 75:301–305

    PubMed  CAS  Google Scholar 

  16. Colleoni M, Price K, Catigione-Gertsch M et al (1998) Dose-response effect of adjuvant cycloposphamide, methotrexate, 5-fluorouracil (CMF) in node-positive breast cancer. Eur J Cancer 34:1693–1700

    Article  PubMed  CAS  Google Scholar 

  17. Bonneterre J, Roche H, Kerbrat P et al (2005) Epirubicin increases long-term survival in adjuvant chemotherapy of patients with poor-prognosis, node-positive, early breast cancer: 10-year follow-up results of the French adjuvant study group 05 randomized trial. J Clin Oncol 23:2686–2693

    Article  PubMed  CAS  Google Scholar 

  18. Hudis C, Citron M, Berry D et al (2005) Five year follow-up of INT C9741: dose-dense chemotherapy is safe and effective. Breast Cancer Res Treat 94:S20

    Google Scholar 

  19. Moliterni A, Bonadonna G, Valagussa P et al (1991) Cyclophosphamide, methotrexate, and fluorouracil with and without doxorubicin in the adjuvant treatment of resectable breast cancer with one to three positive axillary nodes. J Clin Oncol 9:1124–1130

    PubMed  CAS  Google Scholar 

  20. Bonadonna G, Brusamolino E, Valagussa P et al (1976) Combination chemotherapy as an adjuvant treatment in operable breast cancer. N Engl J Med 294:405–410

    Article  PubMed  CAS  Google Scholar 

  21. Buzdar AU, Hortobagyi GN, Kau S-W (1990) Doxorubicin-containing adjuvant therapy for patients with stage II breast cancer: MD Anderson Cancer Center experience. In: Salmon SE (eds) Adjuvant therapy of cancer VI. WB Saunders Co, Philadelphia, PA, pp 210–215

    Google Scholar 

  22. Fisher B, Brown AM, Dimitrov NV et al (1990) Two months of doxorubicin-cyclophosphamide with and without interval reinduction therapy compared with 6 months of cyclophosphamide, methotrexate, and fluorouracil in positive-node breast cancer patients with tamoxifen-non-responsive tumors: Results from the National Surgical Adjuvant Breast and Bowel Project B-15. J Clin Oncol 8:1483–1496

    PubMed  CAS  Google Scholar 

  23. Henderson IC, Berry DA, Demetri GD et al (2003) Improved outcomes from adding sequential paclitaxel but not from escalating doxorubicin dose in an adjuvant chemotherapy regimen for patients with node-positive primary breast cancer. J Clin Oncol 21:976–983

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

The ANC Study Group receives research support from Amgen.

Author information

Authors and Affiliations

  1. James P. Wilmot Cancer Center, University of Rochester Medical Center, 601 Elmwood Avenue, Box 704, Rochester, NY, 14642, USA

    Michelle Shayne, Eva Culakova & Gary H. Lyman

  2. Medical Oncology and Transplantation, Duke University Medical Center, Durham, North Carolina, 27710, USA

    Jeffrey Crawford

  3. Department of Medicine, University of Washington, Seattle, Washington, 98195, USA

    David C. Dale

Authors
  1. Michelle Shayne
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jeffrey Crawford
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. David C. Dale
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Eva Culakova
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Gary H. Lyman
    View author publications

    You can also search for this author in PubMed Google Scholar

Consortia

for the ANC Study Group

Corresponding author

Correspondence to Michelle Shayne.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Shayne, M., Crawford, J., Dale, D.C. et al. Predictors of reduced dose intensity in patients with early-stage breast cancer receiving adjuvant chemotherapy . Breast Cancer Res Treat 100, 255–262 (2006). https://doi.org/10.1007/s10549-006-9254-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10549-006-9254-4

Keywords

Search

Navigation