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Adjuvant Systemic Therapy

Chapter

Abstract

The multidisciplinary treatment of primary breast cancer includes surgery, radiation, and systemic therapy. Approximately two thirds of patients with regional lymph node metastasis recur within 5 years after “curative” resection, presumably due to the presence of undetectable micrometastases that exist at the time of surgery. Therefore, only systemic therapy can eradicate micrometastatic disease and improve long-term disease-free survival. This chapter provides an overview of adjuvant chemotherapy therapy for breast cancer.

Keywords

Breast Cancer Inflammatory Breast Cancer Ovarian Ablation Hazard Reduction Adjuvant Cytotoxic Chemotherapy 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. 1.
    Fisher B. Surgical adjuvant therapy for breast cancer. Cancer. 1972;30:1556–64.PubMedCrossRefGoogle Scholar
  2. 2.
    Fisher B. The evolution of paradigms for the management of breast cancer: a personal perspective. Cancer Res. 1992;52:2371–83.PubMedGoogle Scholar
  3. 3.
    Beatson GT. On the treatment of inoperable cases of carcinoma of the mamma: suggestions for a new method of treatment with illustrative cases. Lancet. 1896;2:104–7.CrossRefGoogle Scholar
  4. 4.
    Boyd S. On oophorectomy in cancer of the breast. BMJ. 1900;2:201061–7.Google Scholar
  5. 5.
    Lett H. An analysis of 99 cases of inoperable carcinoma of the breast treated by oophorectomy. Lancet. 1905;1:227–8.Google Scholar
  6. 6.
    Huggins C, Bergenstal DM. Inhibition of human mammary and prostatic cancers by adrenalectomy. Cancer Res. 1952;12:134–41.PubMedGoogle Scholar
  7. 7.
    Luft R, Olivecrona H. Experiences with hypophysectomy in man. J Neurosurg. 1953;10:301–16.PubMedCrossRefGoogle Scholar
  8. 8.
    Haddow A, Watkinson JM, Paterson E. Influence of synthetic oestrogens upon advanced malignant disease. BMJ. 1944;2:393–8.PubMedCrossRefGoogle Scholar
  9. 9.
    Adjuvant Breast Cancer Trials Collaborative Group. Ovarian ablation or suppression in premenopausal early breast cancer: results from the international adjuvant breast cancer ovarian ablation or suppression randomized trial. J Natl Cancer Inst. 2007;99:516–25.CrossRefGoogle Scholar
  10. 10.
    Jensen EV, Jacobson HI. Fate of steroidal estrogens in target tissues. In: Pincus G, Vollmer EP, editors. Biological activities of steroids in relation to cancer. New York: Academic; 1960.Google Scholar
  11. 2010.
    Toft D, Gorski J. A receptor molecule for estrogens: Isolation from the rat uterus and preliminary characterization. Proc Natl Acad Sci U S A. 1966;55:1574–81.PubMedCrossRefGoogle Scholar
  12. 12.
    McGuire WL, Carbone PP, Vollmer EP. Estrogen receptors in human breast cancer. New York: Raven; 1975.Google Scholar
  13. 13.
    Nolvadex Adjuvant Trial Organisation. Controlled trial of tamoxifen as adjuvant agent in management of early breast cancer. Interim analysis at four years by Nolvadex Adjuvant Trial Organisation. Lancet. 1983;1:257–61.Google Scholar
  14. 14.
    Nolvadex Adjuvant Trial Organisation. Controlled trial of tamoxifen as single adjuvant agent in management of early breast cancer: Analysis at six years by ‘Nolvadex’ Adjuvant Trial Organisation. Lancet. 1985;1:836–40.Google Scholar
  15. 15.
    Gilman A. The initial clinical trial of nitrogen mustard. Am J Surg. 1963;105:574–8.PubMedCrossRefGoogle Scholar
  16. 16.
    Farber S, Diamond LK, Mercer RD, Sylvester RF, Wolff JA. Temporary remissions in acute leukemia in children produced by folic antagonist, 4- aminopteroylglutamic acid (aminopterin). N Engl J Med. 1948;238:787–93.PubMedCrossRefGoogle Scholar
  17. 17.
    Fisher B, Ravdin RG, Ausman RK, Slack NH, Moore GE, Noer RH. Surgical adjuvant chemotherapy in cancer of the breast: results of a decade of cooperative investigation. Ann Surg. 1968;168:337–56.PubMedCrossRefGoogle Scholar
  18. 18.
    Bonadonna G, Brusamolino E, Valagussa P, et al. Combination chemotherapy as an adjuvant treatment in operable breast cancer. N Engl J Med. 1976;294:405–10.PubMedCrossRefGoogle Scholar
  19. 19.
    Bonadonna G, Moliterni A, Zambetti M, et al. 30 years’ follow up of randomised studies of adjuvant CMF in operable breast cancer: cohort study. BMJ. 2005;330:217.PubMedCrossRefGoogle Scholar
  20. 20.
    Englesman E, Klijn JCM, Rubens RD, et al. ‘Classical’ CMF versus a 3-weekly intravenous CMF schedule in postmenopausal patients with advanced breast cancer. An EORTC Breast Cancer Co-operative Group Phase III Trial (10808). Eur J Cancer. 1991;27:966–70.CrossRefGoogle Scholar
  21. 21.
    Miles KW, Ryder K, Rubens RD, Leonard RC, Cameron DA. Comparison of ‘three weekly’ vs. ‘4 weekly’ adjuvant CMF chemotherapy in operable breast cancer. Breast Cancer Res Treat. 2003;82:S29. Abstract 135.Google Scholar
  22. 22.
    Tancini G, Bonadonna G, Valagussa P, Marchini S, Veronesi U. Adjuvant CMF in breast cancer: comparative 5-year results of 12 versus 6 cycles. J Clin Oncol. 1983;1:2–10.PubMedGoogle Scholar
  23. 23.
    Fisher B, Brown AM, Dimitrov NV, et al. 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. 1990;8:1483–96.PubMedGoogle Scholar
  24. 24.
    Fisher B, Anderson S, Tan-Chiu E, et al. Tamoxifen and chemotherapy for axillary node-negative, estrogen receptor-negative breast cancer: findings from National Surgical Adjuvant Breast and Bowel Project B-23. J Clin Oncol. 2001;19:931–42.PubMedGoogle Scholar
  25. 25.
    Piccart MJ, Di Leo A, Beauduin M, et al. Phase III trial comparing two dose levels of epirubicin combined with cyclophosphamide with cyclophosphamide, methotrexate, and fluorouracil in node-positive breast cancer. J Clin Oncol. 2001;19:3103–10.PubMedGoogle Scholar
  26. 26.
    Hutchins LF, Green SJ, Ravdin PM, et al. Randomized, controlled trial of cyclophosphamide, methotrexate, and fluorouracil versus cyclophosphamide, doxorubicin, and fluorouracil with and without tamoxifen for high-risk, node-negative breast cancer: treatment results of Intergroup Protocol INT-0102. J Clin Oncol. 2005;23:8313–21.PubMedCrossRefGoogle Scholar
  27. 27.
    Coombes RC, Bliss JM, Wils J, et al. Adjuvant cyclophosphamide, methotrexate, and fluorouracil versus fluorouracil, epirubicin, and cyclophosphamide chemotherapy in premenopausal women with axillary node-positive operable breast cancer: results of a randomized trial. The International Collaborative Cancer Group. J Clin Oncol. 1996;14:35–45.PubMedGoogle Scholar
  28. 28.
    Misset JL, di Palma M, Delgado M, et al. Adjuvant treatment of node-positive breast cancer with cyclophosphamide, doxorubicin, fluorouracil, and vincristine versus cyclophosphamide, methotrexate, and fluorouracil: final report after a 16-year median follow-up duration. J Clin Oncol. 1996;4:201036–45.Google Scholar
  29. 29.
    Mouridsen HT, Andersen J, Andersson M, et al. Adjuvant anthracycline in breast cancer. Improved outcome in premenopausal patients following substitution of methotrexate in the CMF combination with epirubicin. Proc Am Soc Clin Oncol. 1999;18:68a (Abstract).Google Scholar
  30. 30.
    Levine MN, Pritchard KI, Bramwell VH, Shepherd LE, Tu D, Paul N. Randomized trial ­comparing cyclophosphamide, epirubicin, and fluorouracil with cyclophosphamide, methotrexate, and fluorouracil in premenopausal women with node-positive breast cancer: update of National Cancer Institute of Canada Clinical Trials Group Trial MA5. Clin Oncol. 2005;23: 5166–70.CrossRefGoogle Scholar
  31. 31.
    Poole CJ, Earl HM, Hiller L, et al. Epirubicin and cyclophosphamide, methotrexate, and fluorouracil as adjuvant therapy for early breast cancer. N Engl J Med. 2006;355:1851–62.PubMedCrossRefGoogle Scholar
  32. 32.
    Early Breast Cancer Trialists’ Collaborative Group. Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials. Lancet. 2005;365:1687–717.CrossRefGoogle Scholar
  33. 33.
    Ng R, Green MD. Managing cardiotoxicity in anthracycline-treated breast cancers. Expert Opin Drug Saf. 2007;6:315–21.PubMedCrossRefGoogle Scholar
  34. 34.
    Crump M, Tu D, Shepherd L, Levine M, Bramwell V, Pritchard K. Risk of acute leukemia following epirubicin-based adjuvant chemotherapy: a report from the National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol. 2003;21:3066–71.PubMedCrossRefGoogle Scholar
  35. 35.
    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;21:976–83.PubMedCrossRefGoogle Scholar
  36. 36.
    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;23:3686–96.PubMedCrossRefGoogle Scholar
  37. 37.
    Berry DA, Cirrincione C, Henderson IC, et al. Estrogen-receptor status and outcomes of modern chemotherapy for patients with node-positive breast cancer. JAMA. 2006;295:1658–67.PubMedCrossRefGoogle Scholar
  38. 38.
    Martin M, Pienkowski T, Mackey J, et al. Adjuvant docetaxel for node-positive breast cancer. NEJM. 2005;352:2302–13.PubMedCrossRefGoogle Scholar
  39. 39.
    Roché 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;24:5664–71.PubMedCrossRefGoogle Scholar
  40. 40.
    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;21:1431–9.PubMedCrossRefGoogle Scholar
  41. 41.
    Sparano J, Wang M, Martino S, et al. Phase III study of doxorubicin-cyclophosphamide followed by paclitaxel or docetaxel given every 3 weeks or weekly in operable breast cancer: results of Intergroup Trial E201099. J Clin Oncol. ASCO; 2007:Abstract 516.Google Scholar
  42. 42.
    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;24:5381–7.PubMedCrossRefGoogle Scholar
  43. 43.
    Slamon D, Eirmann W, Robert N, et al. Phase III randomized trial compaing doxorubicin and cyclophosphamide followed by docetaxel with doxorubicin and trastuzumab with docetaxel, carboplatin and trastuzumab in HER2 positive early breast cancer patients: BCIRG 006 study. Breast Cancer Symposium, San Antonio; 2005:Abstract 1.Google Scholar
  44. 44.
    Slamon D, Eiermann W, Robert N, 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. Breast Cancer Symposium, San Antonio; 2009:Abstract 62.Google Scholar
  45. 45.
    Burnell MJ, Levine MN, Chapman JA, et al. A phase III adjuvant trial of sequenced EC + filgrastim + epoetin-alpha followed by paclitaxel compared to sequenced AC followed by paclitaxel compared to CEF in women with node-positive or high-risk node-negative breast cancer (NCIC CTG MA.21). J Clin Oncol. 2007;25s:550.Google Scholar
  46. 46.
    Bezwoda WR, Seymour L, Dansey RD. High-dose chemotherapy with hematopoietic rescue as primary treatment for metastatic breast cancer: a randomized trial. J Clin Oncol. 1995;13:2483–9.PubMedGoogle Scholar
  47. 47.
    Bezwoda WR. Randomized control trial of high dose chemotherapy versus standard dose chemotherapy for high risk surgically treated primary breast cancer (abstract 4). Proc Am Soc Clin Oncol. 1999;18:2a.Google Scholar
  48. 48.
    Rodenhuis S, Bontenbal M, Beex LVAM, et al. High-dose chemotherapy with hematopoietic stem-cell rescue for high-risk breast cancer. N Engl J Med. 2003;349:7–16.PubMedCrossRefGoogle Scholar
  49. 49.
    Nitz UA, Mohrmann S, Fischer J. 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. 2005;366:1935–44.PubMedCrossRefGoogle Scholar
  50. 50.
    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;235:177–82.PubMedCrossRefGoogle Scholar
  51. 51.
    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.PubMedCrossRefGoogle Scholar
  52. 52.
    Romond EH, Perez EA, Bryant J. Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. N Engl J Med. 2005;353:1673–84.PubMedCrossRefGoogle Scholar
  53. 53.
    Perez E, Romond E, Suman V. 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;25:512.CrossRefGoogle Scholar
  54. 54.
    Carlson RW, Anderson BO, Burstein HJ, et al. Invasive breast cancer. J Natl Compr Canc Netw. 2007;5:246–312.PubMedGoogle Scholar
  55. 55.
    Joensuu H, Kellokumpu-Lehtinen PL, Bono P, et al. Adjuvant docetaxel or vinorelbine with or without trastuzumab for breast cancer. N Engl J Med. 2006;354:809–20.PubMedCrossRefGoogle Scholar
  56. 56.
    National Institutes of Health. Clinical trials: Trastuzumab for 6 Months or 1 year in treating women with nonmetastatic breast cancer that can be removed by surgery. 2007. http://clinicaltrials.gov/show/NCT00381901. Accessed 10 Sep 2007.
  57. 57.
  58. 58.
    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;35:2817–26.CrossRefGoogle Scholar
  59. 59.
    National Institutes of Health. Clinical trials: program for the assessment of clinical cancer tests (PACCT-1): trial assigning individualized options for treatment: the TAILORx trial. 2007. http://clinicaltrials.gov/show/NCT00310180. Accessed 10 Sep 2007.
  60. 60.
    Dent R, Trudeau M, Pritchard KI, et al. Triple-negative breast cancer: clinical features and patterns of recurrence. Clin Cancer Res. 2007;13:4429–34.PubMedCrossRefGoogle Scholar
  61. 61.
    National Institutes of Health. Clinical trials: Tykerb evaluation after chemotherapy (TEACH): lapatinib versus placebo in women with early-stage breast cancer. 2007. http://clinicaltrials.gov/show/NCT00374322. Accessed 10 Sep 2007.
  62. 62.
    National Institutes of Health. Clinical trials: adjuvant lapatinib and/or trastuzumab treatment optimisation study (ALTTO). http://clinicaltrials.gov/show/NCT00490139. 2007. Accessed 10 Sep 2007.
  63. 63.
    Pusztai L, Cristofanilli M, Paik S. New generation of molecular prognostic and predictive tests for breast cancer. Semin Oncol. 2007;34:S10–6.PubMedCrossRefGoogle Scholar
  64. 64.
    Buzdar AU, Kau SW, Smith TL, Hortobagyi GN. Ten-year results of FAC adjuvant chemotherapy trial in breast cancer. Am J Clin Oncol. 1989;12:123–8.PubMedCrossRefGoogle Scholar
  65. 65.
    Smalley RV, Carpenter J, Bartolucci A, Vogel C, Krauss S. A comparison of cyclophosphamide, adriamycin, 5-fluorouracil (CAF) and cyclophosphamide, methotrexate, 5-fluorouracil, vincristine, prednisone (CMFVP) in patients with metastatic breast cancer: a Southeastern Cancer Study Group project. Cancer. 1977;40:625–32.PubMedCrossRefGoogle Scholar
  66. 66.
    Bonneterre J, Roché H, Kerbrat P, et al. 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. 2005;23:2686–93.PubMedCrossRefGoogle Scholar
  67. 67.
    Piccart-Gebhart MJ, Procter M, Leyland-Jones B, et al. Trastuzumab after adjuvant chemotherapy in HER-2 positive breast cancer. N Engl J Med. 2005;353:1659–72.PubMedCrossRefGoogle Scholar

Copyright information

© Springer New York 2010

Authors and Affiliations

  1. 1.Department of Medical Oncology and Therapeutics ResearchCity of Hope National Medical CenterDuarteUSA

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