Current Breast Cancer Reports

, Volume 2, Issue 1, pp 16–24 | Cite as

Adjuvant Chemotherapy for Early Stage Breast Cancer: Current Trends and Future Directions



Breast cancer is the most commonly diagnosed cancer among women in the United States. The goal of administering adjuvant therapy to women with early-stage breast cancer is to eradicate clinically occult micrometastatic disease that may later lead to distant recurrence and subsequent death from metastatic disease. Adjuvant chemotherapy has become an integral part of the treatment of early stage cancer. This review highlights some of the major advances in adjuvant chemotherapy, including choice of agents, scheduling, targeted therapy, and the use of molecular profiling techniques.


Adjuvant chemotherapy breast cancer Taxane Trastuzumab Oncotype Dx Anthracycline Bevacizumab Lapatinib 


Papers of particular interest, published recently, have been highlighted as: • Of importance

  1. 1.
    American Cancer Society: Breast Cancer Facts and Figures 2009-2010. Atlanta: American Cancer Society; 2009.Google Scholar
  2. 2.
    Berry DA, Cronin KA, Plevritis SK, et al.: Effect of screening and adjuvant therapy on mortality from breast cancer. N Engl J Med 2005, 353:1784–1792.CrossRefPubMedGoogle Scholar
  3. 3.
    Polychemotherapy for early breast cancer: an overview of the randomised trials. Early Breast Cancer Trialists’ Collaborative Group. Lancet 1998, 352:930–942.Google Scholar
  4. 4.
    Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials. Lancet 2005, 365:1687–1717.Google Scholar
  5. 5.
    Mamounas EP, Bryant J, Lembersky B, et al.: Paclitaxel after doxorubicin plus cyclophosphamide as adjuvant chemotherapy for node-positive breast cancer: results from NSABP B-28. J Clin Oncol 2005, 23:3686–3696.CrossRefPubMedGoogle Scholar
  6. 6.
    Henderson IC, Berry DA, Demetri GD, et al.: 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 2003, 21:976–983.CrossRefPubMedGoogle Scholar
  7. 7.
    Martin M, Pienkowski T, Mackey J, et al.: Adjuvant docetaxel for node-positive breast cancer. N Engl J Med 2005, 352:2302–2313.CrossRefPubMedGoogle Scholar
  8. 8.
    Citron ML, Berry DA, Cirrincione C, et al.: 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 2003, 21:1431–1439.CrossRefPubMedGoogle Scholar
  9. 9.
    Hudis C, Citron ML, Berry DA, et al.: Five year follow-up of INT C9741: dose-dense (DD) chemotherapy (CRx) is safe and effective. Presented at the 28th Annual San Antonio Breast Cancer Symposium. San Antonio, TX; December 2005.Google Scholar
  10. 10.
    Sparano JA, Wang M, Martino S, et al.: Weekly paclitaxel in the adjuvant treatment of breast cancer. N Engl J Med 2008, 358:1663–1671.CrossRefPubMedGoogle Scholar
  11. 11.
    Swain S, Jeong J-H, Geyer C, et al.: NSABP B-30: definitive analysis of patient outcome from a randomized trial evaluating different schedules and combinations of adjuvant therapy containing doxorubicin, docetaxel and cyclophosphamide in women with operable, node-positive breast cancer. Presented at 31st Annual San Antonio Breast Cancer Symposium. San Antonio, TX; December 2008.Google Scholar
  12. 12.
    Eiermann W, Pienkowski T, Crown J, et al: BCIRG 005 main efficacy analysis: a phase III randomized trial comparing docetaxel in combination with doxorubicin and cyclophosphamide (TAC) versus doxorubicin and cyclophosphamide followed by docetaxel (ACT) in women with Her-2/neu negative axillary lymph node positive early breast cancer. Presented at the 31st Annual San Antonio Breast Cancer Symposium. San Antonio, TX; December 2008.Google Scholar
  13. 13.
    Jones SE, Savin MA, Holmes FA, et al.: Phase III trial comparing doxorubicin plus cyclophosphamide with docetaxel plus cyclophosphamide as adjuvant therapy for operable breast cancer. J Clin Oncol 2006, 24:5381–5387.CrossRefPubMedGoogle Scholar
  14. 14.
    • Jones S, Holmes FA, O’Shaughnessy J, et al.: 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 2009, 27:1177–1183. This trial compared 4 cycles of AC versus TC as adjuvant treatment in patients with node-negative or node-positive disease. The TC regimen demonstrated superior DFS and OS, suggesting that taxanes may be used in place of anthracyclines in select patient populations.CrossRefPubMedGoogle Scholar
  15. 15.
    Miller K, Wang M, Gralow J, et al.: Paclitaxel plus bevacizumab versus paclitaxel alone for metastatic breast cancer. N Engl J Med 2007, 357:2666–2676.CrossRefPubMedGoogle Scholar
  16. 16.
    Relf M, LeJeune S, Scott PA, et al.: Expression of the angiogenic factors vascular endothelial cell growth factor, acidic and basic fibroblast growth factor, tumor growth factor beta-1, platelet-derived endothelial cell growth factor, placenta growth factor, and pleiotrophin in human primary breast cancer and its relation to angiogenesis. Cancer Res 1997, 57:963–969.PubMedGoogle Scholar
  17. 17.
    Paik S, Shak S, Tang G, et al.: A multigene assay to predict recurrence of tamoxifen-treated, node-negative breast cancer. N Engl J Med 2004, 351:2817–2826.CrossRefPubMedGoogle Scholar
  18. 18.
    Paik S, Tang G, Shak S, et al.: Gene expression and benefit of chemotherapy in women with node-negative, estrogen receptor-positive breast cancer. J Clin Oncol 2006, 24:3726–3734.CrossRefPubMedGoogle Scholar
  19. 19.
    Albain KS, Barlow WE, Shak S, et al.: Prognostic and predictive value of the 21-gene recurrence score assay in postmenopausal, node-positive, ER-positive breast cancer (S8814,INT0100). Presented at the 29th Annual San Antonio Breast Cancer Symposium. San Antonio, TX; December 2007.Google Scholar
  20. 20.
    Albain K, Barlow W, Shak S, et al.: Prediction of 10-year chemotherapy benefit and breast cancer-specific survival by the 21-gene Recurrence Score (RS) assay in node-positive, er-positive breast cancer—an update of SWOG-8814 (INT0100). Presented at the 32nd Annual San Antonio Breast Cancer Symposium. San Antonio, TX; 2009.Google Scholar
  21. 21.
    Albain KS, Barlow WE, Ravdin PM, et al.: Adjuvant chemotherapy and timing of tamoxifen in postmenopausal patients with endocrine-responsive, node-positive breast cancer: a phase 3, open-label, randomised controlled trial. Lancet 2009 (in press).Google Scholar
  22. 22.
    Slamon DJ, Clark GM, Wong SG, et al.: Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science 1987, 235:177–182.CrossRefPubMedGoogle Scholar
  23. 23.
    Kallioniemi OP, Holli K, Visakorpi T, et al.: Association of c-erbB-2 protein over-expression with high rate of cell proliferation, increased risk of visceral metastasis and poor long-term survival in breast cancer. Int J Cancer 1991, 49:650–655.CrossRefPubMedGoogle Scholar
  24. 24.
    Slamon DJ, Leyland-Jones B, Shak S, et al.: Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med 2001, 344:783–792.CrossRefPubMedGoogle Scholar
  25. 25.
    Romond EH, Perez EA, Bryant J, et al.: Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. N Engl J Med 2005, 353:1673–1684.CrossRefPubMedGoogle Scholar
  26. 26.
    Perez EA, Romond E, Suman V, et al.: Updated results of the combined analysis of NCCTG N9831 and NSABP B-31 adjuvant chemotherapy with/without trastuzumab in patients with HER2-positive breast cancer. J Clin Oncol 2007, 25(18 S):abstract 512.Google Scholar
  27. 27.
    Perez EA, Suman V, Davidson N, et al.: Results of chemotherapy alone, with sequential or concurrent addition of 52 weeks of trastuzumab in the NCCTG N9831 HER2-Positive adjuvant breast cancer trial. Presented at the 32nd Annual San Antonio Breast Cancer Symposium. San Antonio, TX; December 2009.Google Scholar
  28. 28.
    Piccart-Gebhart MJ, Procter M, Leyland-Jones B, et al.: Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer. N Engl J Med 2005, 353:1659–1672.CrossRefPubMedGoogle Scholar
  29. 29.
    Smith I, Procter M, Gelber RD, et al.: 2-year follow-up of trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer: a randomised controlled trial. Lancet 2007, 369:29–36.CrossRefPubMedGoogle Scholar
  30. 30.
    Gianni L: Update of the HERA trial at 4 years' median follow-up. Presented at the St. Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer. St. Gallen, Switzerland; 2009.Google Scholar
  31. 31.
    • Slamon DJ, Eiermann W, Pienkowski T, et al.: Phase III Randomized trial comparing doxorubicin and cyclophosphamide followed by docetaxel (AC→T) with doxorubicin and cyclophosphamide followed by docetaxel and trastuzumab (AC→TH) with docetaxel, carboplatin and trastuzumab (TCH) in Her2neu Positive early breast cancer patients: BCIRG 006 Study. Presented at the 32nd Annual San Antonio Breast Cancer Symposium. San Antonio, TX; 2009. This was the only adjuvant trastuzumab trial that included a non–anthracycline-containing arm. Patients were randomized to AC→T versus AC→TH versus TCH. The two trastuzumab-containing arms showed improved DFS and OS compared with the control group. Although DFS for AC→TH was numerically superior to TCH, this was not statistically significant, and there were more cardiac toxicities and secondary leukemias seen with AC→TH.Google Scholar
  32. 32.
    Joensuu H, Bono P, Kataja V, et al.: Fluorouracil, epirubicin, and cyclophosphamide with either docetaxel or vinorelbine, with or without trastuzumab, as adjuvant treatments of breast cancer: final results of the FinHer Trial. J Clin Oncol 2009, 27:5685–5692.CrossRefPubMedGoogle Scholar
  33. 33.
    Gonzalez-Angulo AM, Litton JK, Broglio KR, et al.: High risk of recurrence for patients with breast cancer who have human epidermal growth factor receptor 2-positive, node-negative tumors 1 cm or smaller. J Clin Oncol 2009, 27:5700–5706.CrossRefPubMedGoogle Scholar
  34. 34.
    Curigliano G, Viale G, Bagnardi V, et al.: Clinical relevance of HER2 overexpression/amplification in patients with small tumor size and node-negative breast cancer. J Clin Oncol 2009, 27:5693–5699.CrossRefPubMedGoogle Scholar
  35. 35.
    Kaufman B, Mackey JR, Clemens MR, et al.: Trastuzumab plus anastrozole versus anastrozole alone for the treatment of postmenopausal women with human epidermal growth factor receptor 2-positive, hormone receptor-positive metastatic breast cancer: results from the randomized phase III TAnDEM study. J Clin Oncol 2009, 27:5529–5537.CrossRefPubMedGoogle Scholar
  36. 36.
    Johnston S, Pegram M, Press M, et al.: Lapatinib combined with letrozole vs. letrozole alone for front line postmenopausal hormone receptor positive (HR+) metastatic breast cancer (MBC): first results from the EGF30008 Trial. Presented at the 31st Annual San Antonio Breast Cancer Sympsium. San Antonio, TX; December 2008.Google Scholar
  37. 37.
    Konecny GE, Meng YG, Untch M, et al.: Association between HER-2/neu and vascular endothelial growth factor expression predicts clinical outcome in primary breast cancer patients. Clin Cancer Res 2004, 10:1706–1716.CrossRefPubMedGoogle Scholar
  38. 38.
    Roche H, Fumoleau P, Spielmann M, et al.: Sequential adjuvant epirubicin-based and docetaxel chemotherapy for node-positive breast cancer patients: the FNCLCC PACS 01 Trial. J Clin Oncol 2006, 24:5664–5671.CrossRefPubMedGoogle Scholar
  39. 39.
    Burnell M, Levine MN, Chapman JA, et al.: Cyclophosphamide, epirubicin, and fluorouracil versus dose-dense epirubicin and cyclophosphamide followed by paclitaxel versus doxorubicin and cyclophosphamide followed by paclitaxel in node-positive or high-risk node-negative breast cancer. J Clin Oncol 2009 (in press).Google Scholar

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  1. 1.Division of Medical Oncology, UMDNJ—Robert Wood Johnson Medical SchoolThe Cancer Institute of New JerseyNew BrunswickUSA

Personalised recommendations