Skip to main content

Advertisement

SpringerLink
Log in

A retrospective evaluation of chemotherapy dose intensity and supportive care for early-stage breast cancer in a curative setting

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

Abstract

Early-stage breast cancer (ESBC) is commonly treated with myelosuppressive chemotherapy, and maintaining full-dose chemotherapy on the planned schedule is associated with improved patient outcome. Retrospective analysis of patients with ESBC treated from 1997 to 2000 showed that 56 % of patients received a relative dose intensity (RDI) <85 % (Lyman et al., J Clin Oncol 21(24):4524–4531, 2003). To determine current practice, we evaluated treatment patterns at 24 US community- and hospital-based oncology practices, 79 % of which participated in the previous study. Data were abstracted from medical records of 532 patients with surgically resected ESBC (stage I–IIIa) treated from 2007 to 2009, who were ≥18 years old and had completed ≥1 cycle of one of the following regimens: docetaxel + cyclophosphamide (TC); doxorubicin + cyclophosphamide (AC); AC followed by paclitaxel (AC-T); docetaxel + carboplatin + trastuzumab (TCH); or docetaxel + doxorubicin + cyclophosphamide (TAC). Endpoints included RDI, dose delays, dose reductions, grade 3/4 neutropenia, febrile neutropenia (FN), FN-related hospitalization, granulocyte colony-stimulating factor (G-CSF) use, and antimicrobial use. In this study, TC was the most common chemotherapy regimen (42 %), and taxane-based chemotherapy regimens were more common relative to the previously published results (89 vs <4 %). Overall, 83.8 % of patients received an RDI ≥85 %, an improvement over the previous study where 44.5 % received an RDI ≥85 %. Other changes seen between this and the previous study included a lower incidence of dose delays (16 vs 25 %) and dose reductions (21 vs 37 %) and increased use of primary prophylactic G-CSF (76 vs ~3 %). Here, 40 % of patients had grade 3/4 neutropenia, 3 % had FN, 2 % had an FN-related hospitalization, and 30 % received antimicrobial therapy; these measures were not available in the previously published results. Though RDI was higher here than in the previous study, 16.2 % of patients still received an RDI <85 %. Understanding factors that contribute to reduced RDI may further improve chemotherapy delivery, and ultimately, patient outcomes.

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

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Bonadonna G, Brusamolino E, Valagussa P, Rossi A, Brugnatelli L, Brambilla C, De Lena M, Tancini G, Bajetta E, Musumeci R, Veronesi U (1976) Combination chemotherapy as an adjuvant treatment in operable breast cancer. N Engl J Med 294(8):405–410. doi:10.1056/NEJM197602192940801

    Article  PubMed  CAS  Google Scholar 

  2. Rossi A, Bonadonna G, Valagussa P, Veronesi U (1981) Multimodal treatment in operable breast cancer: five-year results of the CMF programme. Br Med J (Clin Res Ed) 282(6274):1427–1431

    Article  CAS  Google Scholar 

  3. EBCTCG (2011) Comparisons between different polychemotherapy regimens for early breast cancer: meta-analyses of long-term outcome among 100,000 women in 123 randomised trials. Lancet 379(9814):4–10

    Google Scholar 

  4. Fisher B, Brown AM, Dimitrov NV, Poisson R, Redmond C, Margolese RG, Bowman D, Wolmark N, Wickerham DL, Kardinal CG 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-nonresponsive tumors: results from the National Surgical Adjuvant Breast and Bowel Project B-15. J Clin Oncol 8(9):1483–1496

    PubMed  CAS  Google Scholar 

  5. Fisher B, Jeong JH, Anderson S, Wolmark N (2004) Treatment of axillary lymph node-negative, estrogen receptor-negative breast cancer: updated findings from National Surgical Adjuvant Breast and Bowel Project clinical trials. J Natl Cancer Inst 96(24):1823–1831. doi:10.1093/jnci/djh338

    Article  PubMed  Google Scholar 

  6. Jones SE, Moon TE, Bonadonna G, Valagussa P, Rivkin S, Buzdar A, Montague E, Powles T (1987) Comparison of different trials of adjuvant chemotherapy in stage II breast cancer using a natural history data base. Am J Clin Oncol 10(5):387–395

    Article  PubMed  CAS  Google Scholar 

  7. Peto R, Davies C, Godwin J, Gray R, Pan HC, Clarke M, Cutter D, Darby S, McGale P, Taylor C, Wang YC, Bergh J, Di Leo A, Albain K, Swain S, Piccart M, Pritchard K (2012) Comparisons between different polychemotherapy regimens for early breast cancer: meta-analyses of long-term outcome among 100,000 women in 123 randomised trials. Lancet 379(9814):432–444. doi:10.1016/S0140-6736(11)61625-5

    Article  PubMed  CAS  Google Scholar 

  8. Henderson IC, Berry DA, Demetri GD, Cirrincione CT, Goldstein LJ, Martino S, Ingle JN, Cooper MR, Hayes DF, Tkaczuk KH, Fleming G, Holland JF, Duggan DB, Carpenter JT, Frei E 3rd, Schilsky RL, Wood WC, Muss HB, Norton L (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(6):976–983

    Article  PubMed  CAS  Google Scholar 

  9. Martin M, Pienkowski T, Mackey J, Pawlicki M, Guastalla JP, Weaver C, Tomiak E, Al-Tweigeri T, Chap L, Juhos E, Guevin R, Howell A, Fornander T, Hainsworth J, Coleman R, Vinholes J, Modiano M, Pinter T, Tang SC, Colwell B, Prady C, Provencher L, Walde D, Rodriguez-Lescure A, Hugh J, Loret C, Rupin M, Blitz S, Jacobs P, Murawsky M, Riva A, Vogel C (2005) Adjuvant docetaxel for node-positive breast cancer. N Engl J Med 352(22):2302–2313. doi:10.1056/NEJMoa043681

    Article  PubMed  CAS  Google Scholar 

  10. Jones SE, Savin MA, Holmes FA, O’Shaughnessy JA, Blum JL, Vukelja S, McIntyre KJ, Pippen JE, Bordelon JH, Kirby R, Sandbach J, Hyman WJ, Khandelwal P, Negron AG, Richards DA, Anthony SP, Mennel RG, Boehm KA, Meyer WG, Asmar L (2006) Phase III trial comparing doxorubicin plus cyclophosphamide with docetaxel plus cyclophosphamide as adjuvant therapy for operable breast cancer. J Clin Oncol 24(34):5381–5387. doi:10.1200/JCO.2006.06.5391

    Article  PubMed  CAS  Google Scholar 

  11. Citron ML, Berry DA, Cirrincione C, Hudis C, Winer EP, Gradishar WJ, Davidson NE, Martino S, Livingston R, Ingle JN, Perez EA, Carpenter J, Hurd D, Holland JF, Smith BL, Sartor CI, Leung EH, Abrams J, Schilsky RL, Muss HB, Norton L (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(8):1431–1439

    Article  PubMed  CAS  Google Scholar 

  12. EBCTCG (2005) Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials. Lancet 365(9472):1687–1717

    Article  Google Scholar 

  13. Berry DA, Cronin KA, Plevritis SK, Fryback DG, Clarke L, Zelen M, Mandelblatt JS, Yakovlev AY, Habbema JD, Feuer EJ (2005) Effect of screening and adjuvant therapy on mortality from breast cancer. N Engl J Med 353(17):1784–1792. doi:10.1056/NEJMoa050518

    Article  PubMed  CAS  Google Scholar 

  14. DeSantis C, Siegel R, Bandi P, Jemal A (2011) Breast cancer statistics. CA Cancer J Clin 61(6):409–418. doi:10.3322/caac.20134

    Article  PubMed  Google Scholar 

  15. American Cancer Society (2012) Cancer Facts and Figures 2012

  16. Hryniuk WM, Figueredo A, Goodyear M (1987) Applications of dose intensity to problems in chemotherapy of breast and colorectal cancer. Semin Oncol 14(4 Suppl 4):3–11

    PubMed  CAS  Google Scholar 

  17. Budman DR, Berry DA, Cirrincione CT, Henderson IC, Wood WC, Weiss RB, Ferree CR, Muss HB, Green MR, Norton L, Frei E 3rd (1998) Dose and dose intensity as determinants of outcome in the adjuvant treatment of breast cancer. The Cancer and Leukemia Group B. J Natl Cancer Inst 90(16):1205–1211. doi:10.1093/jnci/90.16.1205

    Article  PubMed  CAS  Google Scholar 

  18. Chirivella I, Bermejo B, Insa A, Perez-Fidalgo A, Magro A, Rosello S, Garcia-Garre E, Martin P, Bosch A, Lluch A (2009) Optimal delivery of anthracycline-based chemotherapy in the adjuvant setting improves outcome of breast cancer patients. Breast Cancer Res Treat 114(3):479–484. doi:10.1007/s10549-008-0018-1

    Article  PubMed  CAS  Google Scholar 

  19. Lyman GH (2009) Impact of chemotherapy dose intensity on cancer patient outcomes. J Natl Compr Cancer Netw 7(1):99–108

    Google Scholar 

  20. 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(24):4524–4531. doi:10.1200/JCO.2003.05.002

    Article  PubMed  Google Scholar 

  21. Giordano SH, Lin YL, Kuo YF, Hortobagyi GN, Goodwin JS (2012) Decline in the use of anthracyclines for breast cancer. J Clin Oncol 30(18):2232–2239. doi:10.1200/JCO.2011.40.1273

    Article  PubMed  CAS  Google Scholar 

  22. NCCN Clinical Practice Guidelines in Oncology: Breast Cancer. v3.2013

  23. Wildiers H, Reiser M (2011) Relative dose intensity of chemotherapy and its impact on outcomes in patients with early breast cancer or aggressive lymphoma. Crit Rev Oncol Hematol 77(3):221–240. doi:10.1016/j.critrevonc.2010.02.002

    Article  PubMed  Google Scholar 

  24. Kemeny MM, Peterson BL, Kornblith AB, Muss HB, Wheeler J, Levine E, Bartlett N, Fleming G, Cohen HJ (2003) Barriers to clinical trial participation by older women with breast cancer. J Clin Oncol 21(12):2268–2275. doi:10.1200/JCO.2003.09.124

    Article  PubMed  Google Scholar 

  25. Muss HB, Woolf S, Berry D, Cirrincione C, Weiss RB, Budman D, Wood WC, Henderson IC, Hudis C, Winer E, Cohen H, Wheeler J, Norton L (2005) Adjuvant chemotherapy in older and younger women with lymph node-positive breast cancer. JAMA 293(9):1073–1081. doi:10.1001/jama.293.9.1073

    Article  PubMed  CAS  Google Scholar 

  26. Griggs JJ, Mangu PB, Anderson H, Balaban EP, Dignam JJ, Hryniuk WM, Morrison VA, Pini TM, Runowicz CD, Rosner GL, Shayne M, Sparreboom A, Sucheston LE, Lyman GH (2012) Appropriate chemotherapy dosing for obese adult patients with cancer: American Society of Clinical Oncology clinical practice guideline. J Clin Oncol 30(13):1553–1561. doi:10.1200/JCO.2011.39.9436

    Article  PubMed  Google Scholar 

  27. (1985) Consensus conference. Adjuvant chemotherapy for breast cancer. JAMA 254(24):3461–3463

  28. Eifel P, Axelson JA, Costa J, Crowley J, Curran WJ Jr, Deshler A, Fulton S, Hendricks CB, Kemeny M, Kornblith AB, Louis TA, Markman M, Mayer R, Roter D (2001) National Institutes of Health Consensus Development Conference Statement: adjuvant therapy for breast cancer, November 1–3, 2000. J Natl Cancer Inst 93(13):979–989

    Article  PubMed  CAS  Google Scholar 

  29. Neugut AI, Hillyer GC, Kushi LH, Lamerato L, Leoce N, Nathanson SD, Ambrosone CB, Bovbjerg DH, Mandelblatt JS, Magai C, Tsai WY, Jacobson JS, Hershman DL (2012) Noninitiation of adjuvant chemotherapy in women with localized breast cancer: the breast cancer quality of care study. J Clin Oncol 30(31):3800–3809. doi:10.1200/JCO.2012.43.8168

    Article  PubMed  Google Scholar 

  30. Shen Y, Dong W, Feig BW, Ravdin P, Theriault RL, Giordano SH (2009) Patterns of treatment for early stage breast cancers at the M. D. Anderson Cancer Center from 1997 to 2004. Cancer 115(10):2041. doi:10.1002/cncr.24271

    Article  PubMed  Google Scholar 

  31. Jones S, Holmes FA, O’Shaughnessy J, Blum JL, Vukelja SJ, McIntyre KJ, Pippen JE, Bordelon JH, Kirby RL, Sandbach J, Hyman WJ, Richards DA, Mennel RG, Boehm KA, Meyer WG, Asmar L, Mackey D, Riedel S, Muss H, Savin MA (2009) Docetaxel with cyclophosphamide is associated with an overall survival benefit compared with doxorubicin and cyclophosphamide: 7-year follow-up of US Oncology Research Trial 9735. J Clin Oncol 27(8):1177–1183

    Article  PubMed  CAS  Google Scholar 

  32. Chan A, Fu WH, Shih V, Coyuco JC, Tan SH, Ng R (2011) Impact of colony-stimulating factors to reduce febrile neutropenic events in breast cancer patients receiving docetaxel plus cyclophosphamide chemotherapy. Support Care Cancer 19(4):497–504. doi:10.1007/s00520-010-0843-8

    Article  PubMed  Google Scholar 

  33. Soong D, Haj R, Leung MG, Myers R, Higgins B, Myers J, Rajagopal S (2009) High rate of febrile neutropenia in patients with operable breast cancer receiving docetaxel and cyclophosphamide. J Clin Oncol 27(26):e101–e102. doi:10.1200/JCO.2009.23.0508

    Article  PubMed  Google Scholar 

  34. Vandenberg T, Younus J, Al-Khayyat S (2010) Febrile neutropenia rates with adjuvant docetaxel and cyclophosphamide chemotherapy in early breast cancer: discrepancy between published reports and community practice—a retrospective analysis. Curr Oncol 17(2):2–3

    Article  PubMed  CAS  Google Scholar 

  35. Aapro MS, Bohlius J, Cameron DA, Dal Lago L, Donnelly JP, Kearney N, Lyman GH, Pettengell R, Tjan-Heijnen VC, Walewski J, Weber DC, Zielinski C (2011) 2010 update of EORTC guidelines for the use of granulocyte-colony stimulating factor to reduce the incidence of chemotherapy-induced febrile neutropenia in adult patients with lymphoproliferative disorders and solid tumours. Eur J Cancer 47(1):8–32. doi:10.1016/j.ejca.2010.10.013

    Article  PubMed  CAS  Google Scholar 

  36. Smith TJ, Khatcheressian J, Lyman GH, Ozer H, Armitage JO, Balducci L, Bennett CL, Cantor SB, Crawford J, Cross SJ, Demetri G, Desch CE, Pizzo PA, Schiffer CA, Schwartzberg L, Somerfield MR, Somlo G, Wade JC, Wade JL, Winn RJ, Wozniak AJ, Wolff AC (2006) 2006 Update of recommendations for the use of white blood cell growth factors: an evidence-based clinical practice guideline. J Clin Oncol 24(19):3187–3205. doi:10.1200/JCO.2006.06.4451

    Article  PubMed  CAS  Google Scholar 

  37. NCCN Clinical Practice Guidelines in Oncology: Myeloid Growth Factors. v1.2012

Download references

Acknowledgments

The authors thank Greg Valin, Sharon Hunter, Natasha Gicanov, Paul Chang, and Sejal Badre (Amgen Inc.) for their contributions to this study. Kerri Hebard-Massey, PhD (Amgen Inc.) provided writing assistance. This study was funded by Amgen Inc.

Conflict of interest

GHL is principal investigator of a research grant to Duke University from Amgen in support of the ANC Study Group. DCD and JC received research funding from and are on an advisory board of Amgen Inc. DT and SW are employees of and stockholders in Amgen Inc.

Author information

Authors and Affiliations

  1. Duke Cancer Institute, Duke University, 2424 Erwin Road, Suite 205, Durham, NC, 27705, USA

    Gary H. Lyman & Jeffrey Crawford

  2. University of Washington, 1959 NE Pacific Street, Seattle, WA, 98195, USA

    David C. Dale

  3. Amgen Inc., One Amgen Center Way, Thousand Oaks, CA, 91360, USA

    Dianne Tomita & Sadie Whittaker

Authors
  1. Gary H. Lyman
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. David C. Dale
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Dianne Tomita
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Sadie Whittaker
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jeffrey Crawford
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Gary H. Lyman.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOC 123 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lyman, G.H., Dale, D.C., Tomita, D. et al. A retrospective evaluation of chemotherapy dose intensity and supportive care for early-stage breast cancer in a curative setting. Breast Cancer Res Treat 139, 863–872 (2013). https://doi.org/10.1007/s10549-013-2582-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10549-013-2582-2

Keywords

Search

Navigation