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Systemic treatment of metastatic breast cancer in women: Chemotherapy

Author
Anne F Schott, MD
Section Editor
Daniel F Hayes, MD
Deputy Editor
Sadhna R Vora, MD

INTRODUCTION

Breast cancer is the most frequently diagnosed cancer and the leading cause of cancer-related death among females worldwide [1]. Despite the gains in early detection, up to five percent of women diagnosed with breast cancer in the United States have metastatic disease at the time of first presentation. In addition, up to 30 percent of women with early-stage, non-metastatic breast cancer at diagnosis will develop distant metastatic disease [2]. Although metastatic breast cancer is not curable, meaningful improvements in survival have been seen, coincident with the introduction of newer systemic therapies [3-5].

The role of chemotherapy for the treatment of metastatic breast cancer will be reviewed here. A general overview of the approach to metastatic breast cancer, endocrine therapy for hormone receptor-positive metastatic breast cancer, Human Epidermal Growth Factor Receptor 2 (HER2)-directed agents and other molecularly targeted therapy, and breast cancer in men are reviewed separately. In addition, commonly used treatment regimens used in the treatment of breast cancer are also compiled in a separate topic.

(See "Systemic treatment for metastatic breast cancer: General principles".)

(See "Treatment approach to metastatic hormone receptor-positive breast cancer: Endocrine therapy".)

(See "Systemic treatment for HER2-positive metastatic breast cancer".)

                                    

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Literature review current through: Nov 2016. | This topic last updated: Fri Aug 21 00:00:00 GMT 2015.
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References
Top
  1. Breast Cancer. http://www.cancerresearchuk.org/cancer-info/cancerstats/world/breast-cancer-world/ (Accessed on March 04, 2013).
  2. Early Breast Cancer Trialists' Collaborative Group (EBCTCG). 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.
  3. Chia SK, Speers CH, D'yachkova Y, et al. The impact of new chemotherapeutic and hormone agents on survival in a population-based cohort of women with metastatic breast cancer. Cancer 2007; 110:973.
  4. Gennari A, Conte P, Rosso R, et al. Survival of metastatic breast carcinoma patients over a 20-year period: a retrospective analysis based on individual patient data from six consecutive studies. Cancer 2005; 104:1742.
  5. Dafni U, Grimani I, Xyrafas A, et al. Fifteen-year trends in metastatic breast cancer survival in Greece. Breast Cancer Res Treat 2010; 119:621.
  6. Wilcken N, Hornbuckle J, Ghersi D. Chemotherapy alone versus endocrine therapy alone for metastatic breast cancer. Cochrane Database Syst Rev 2003; :CD002747.
  7. Pritchard KI, Paterson AH, Paul NA, et al. Increased thromboembolic complications with concurrent tamoxifen and chemotherapy in a randomized trial of adjuvant therapy for women with breast cancer. National Cancer Institute of Canada Clinical Trials Group Breast Cancer Site Group. J Clin Oncol 1996; 14:2731.
  8. Fossati R, Confalonieri C, Torri V, et al. Cytotoxic and hormonal treatment for metastatic breast cancer: a systematic review of published randomized trials involving 31,510 women. J Clin Oncol 1998; 16:3439.
  9. Dear RF, McGeechan K, Jenkins MC, et al. Combination versus sequential single agent chemotherapy for metastatic breast cancer. Cochrane Database Syst Rev 2013; :CD008792.
  10. Carrick S, Parker S, Thornton CE, et al. Single agent versus combination chemotherapy for metastatic breast cancer. Cochrane Database Syst Rev 2009; :CD003372.
  11. Smith IC, Heys SD, Hutcheon AW, et al. Neoadjuvant chemotherapy in breast cancer: significantly enhanced response with docetaxel. J Clin Oncol 2002; 20:1456.
  12. Mauri D, Kamposioras K, Tsali L, et al. Overall survival benefit for weekly vs. three-weekly taxanes regimens in advanced breast cancer: A meta-analysis. Cancer Treat Rev 2010; 36:69.
  13. Sparano JA, Wang M, Martino S, et al. Weekly paclitaxel in the adjuvant treatment of breast cancer. N Engl J Med 2008; 358:1663.
  14. Piccart MJ, Klijn J, Paridaens R, et al. Corticosteroids significantly delay the onset of docetaxel-induced fluid retention: final results of a randomized study of the European Organization for Research and Treatment of Cancer Investigational Drug Branch for Breast Cancer. J Clin Oncol 1997; 15:3149.
  15. Seidman AD, Berry D, Cirrincione C, et al. Randomized phase III trial of weekly compared with every-3-weeks paclitaxel for metastatic breast cancer, with trastuzumab for all HER-2 overexpressors and random assignment to trastuzumab or not in HER-2 nonoverexpressors: final results of Cancer and Leukemia Group B protocol 9840. J Clin Oncol 2008; 26:1642.
  16. Ibrahim NK, Samuels B, Page R, et al. Multicenter phase II trial of ABI-007, an albumin-bound paclitaxel, in women with metastatic breast cancer. J Clin Oncol 2005; 23:6019.
  17. Gradishar WJ, Tjulandin S, Davidson N, et al. Phase III trial of nanoparticle albumin-bound paclitaxel compared with polyethylated castor oil-based paclitaxel in women with breast cancer. J Clin Oncol 2005; 23:7794.
  18. Gradishar WJ, Krasnojon D, Cheporov S, et al. Significantly longer progression-free survival with nab-paclitaxel compared with docetaxel as first-line therapy for metastatic breast cancer. J Clin Oncol 2009; 27:3611.
  19. Jones SE, Erban J, Overmoyer B, et al. Randomized phase III study of docetaxel compared with paclitaxel in metastatic breast cancer. J Clin Oncol 2005; 23:5542.
  20. Rugo HS, Barry WT, Moreno-Aspitia A, et al. Randomized Phase III Trial of Paclitaxel Once Per Week Compared With Nanoparticle Albumin-Bound Nab-Paclitaxel Once Per Week or Ixabepilone With Bevacizumab As First-Line Chemotherapy for Locally Recurrent or Metastatic Breast Cancer: CALGB 40502/NCCTG N063H (Alliance). J Clin Oncol 2015; 33:2361.
  21. Norris B, Pritchard KI, James K, et al. Phase III comparative study of vinorelbine combined with doxorubicin versus doxorubicin alone in disseminated metastatic/recurrent breast cancer: National Cancer Institute of Canada Clinical Trials Group Study MA8. J Clin Oncol 2000; 18:2385.
  22. Andersson M, Daugaard S, von der Maase H, Mouridsen HT. Doxorubicin versus mitomycin versus doxorubicin plus mitomycin in advanced breast cancer: a randomized study. Cancer Treat Rep 1986; 70:1181.
  23. Joensuu H, Holli K, Heikkinen M, et al. Combination chemotherapy versus single-agent therapy as first- and second-line treatment in metastatic breast cancer: a prospective randomized trial. J Clin Oncol 1998; 16:3720.
  24. Ejlertsen B, Mouridsen HT, Langkjer ST, et al. Phase III study of intravenous vinorelbine in combination with epirubicin versus epirubicin alone in patients with advanced breast cancer: a Scandinavian Breast Group Trial (SBG9403). J Clin Oncol 2004; 22:2313.
  25. Nielsen D, Dombernowsky P, Larsen SK, et al. Epirubicin or epirubicin and cisplatin as first-line therapy in advanced breast cancer. A phase III study. Cancer Chemother Pharmacol 2000; 46:459.
  26. O'Brien ME, Wigler N, Inbar M, et al. Reduced cardiotoxicity and comparable efficacy in a phase III trial of pegylated liposomal doxorubicin HCl (CAELYX/Doxil) versus conventional doxorubicin for first-line treatment of metastatic breast cancer. Ann Oncol 2004; 15:440.
  27. Keller AM, Mennel RG, Georgoulias VA, et al. Randomized phase III trial of pegylated liposomal doxorubicin versus vinorelbine or mitomycin C plus vinblastine in women with taxane-refractory advanced breast cancer. J Clin Oncol 2004; 22:3893.
  28. Piccart-Gebhart MJ, Burzykowski T, Buyse M, et al. Taxanes alone or in combination with anthracyclines as first-line therapy of patients with metastatic breast cancer. J Clin Oncol 2008; 26:1980.
  29. Kopf B, De Giorgi U, Zago S, et al. Innovative therapy for patients with brain metastases: oral treatments. J Chemother 2004; 16 Suppl 5:94.
  30. Fumoleau P, Largillier R, Clippe C, et al. Multicentre, phase II study evaluating capecitabine monotherapy in patients with anthracycline- and taxane-pretreated metastatic breast cancer. Eur J Cancer 2004; 40:536.
  31. Oshaughnessy JA, Blum J, Moiseyenko V, et al. Randomized, open-label, phase II trial of oral capecitabine (Xeloda) vs. a reference arm of intravenous CMF (cyclophosphamide, methotrexate and 5-fluorouracil) as first-line therapy for advanced/metastatic breast cancer. Ann Oncol 2001; 12:1247.
  32. Cortes J, O'Shaughnessy J, Loesch D, et al. Eribulin monotherapy versus treatment of physician's choice in patients with metastatic breast cancer (EMBRACE): a phase 3 open-label randomised study. Lancet 2011; 377:914.
  33. Kaufman PA, Awada A, Twelves C, et al. Phase III open-label randomized study of eribulin mesylate versus capecitabine in patients with locally advanced or metastatic breast cancer previously treated with an anthracycline and a taxane. J Clin Oncol 2015; 33:594.
  34. Vogel C, O'Rourke M, Winer E, et al. Vinorelbine as first-line chemotherapy for advanced breast cancer in women 60 years of age or older. Ann Oncol 1999; 10:397.
  35. Martín M, Ruiz A, Muñoz M, et al. Gemcitabine plus vinorelbine versus vinorelbine monotherapy in patients with metastatic breast cancer previously treated with anthracyclines and taxanes: final results of the phase III Spanish Breast Cancer Research Group (GEICAM) trial. Lancet Oncol 2007; 8:219.
  36. Fumoleau P, Delgado FM, Delozier T, et al. Phase II trial of weekly intravenous vinorelbine in first-line advanced breast cancer chemotherapy. J Clin Oncol 1993; 11:1245.
  37. Jones S, Winer E, Vogel C, et al. Randomized comparison of vinorelbine and melphalan in anthracycline-refractory advanced breast cancer. J Clin Oncol 1995; 13:2567.
  38. Gridelli C, Perrone F, Gallo C, et al. Single-agent gemcitabine as second-line treatment in patients with advanced non small cell lung cancer (NSCLC): a phase II trial. Anticancer Res 1999; 19:4535.
  39. Rha SY, Moon YH, Jeung HC, et al. Gemcitabine monotherapy as salvage chemotherapy in heavily pretreated metastatic breast cancer. Breast Cancer Res Treat 2005; 90:215.
  40. Blackstein M, Vogel CL, Ambinder R, et al. Gemcitabine as first-line therapy in patients with metastatic breast cancer: a phase II trial. Oncology 2002; 62:2.
  41. Feher O, Vodvarka P, Jassem J, et al. First-line gemcitabine versus epirubicin in postmenopausal women aged 60 or older with metastatic breast cancer: a multicenter, randomized, phase III study. Ann Oncol 2005; 16:899.
  42. Perez EA, Lerzo G, Pivot X, et al. Efficacy and safety of ixabepilone (BMS-247550) in a phase II study of patients with advanced breast cancer resistant to an anthracycline, a taxane, and capecitabine. J Clin Oncol 2007; 25:3407.
  43. Rugo HS, Barry WT, Moreno-Aspitia A, et al. CALGB 40502/NCCTG N063H: Randomized phase III trial of weekly paclitaxel (P) compared to weekly nanoparticle albumin bound nab-paclitaxel (NP) or ixabepilone (Ix) with or without bevacizumab (B) as first-line therapy for locally recurrent or metastatic breast cancer (MBC). J Clin Oncol 2012; 30:(suppl; abstr CRA1002).
  44. Brunden KR, Ballatore C, Lee VM, et al. Brain-penetrant microtubule-stabilizing compounds as potential therapeutic agents for tauopathies. Biochem Soc Trans 2012; 40:661.
  45. European Medicines Agency (EMEA) Committee for Medicinal Products for Human Use (CHMP) recommendation for refusal of marketing authorization for ixabepilone, available online at http://www.esmo.org/no_cache/view-news.html?tx_ttnews[tt_news]=480&tx_ttnews[backPid]=585&cHash=9385b0342b .
  46. Denduluri N, Low JA, Lee JJ, et al. Phase II trial of ixabepilone, an epothilone B analog, in patients with metastatic breast cancer previously untreated with taxanes. J Clin Oncol 2007; 25:3421.
  47. Low JA, Wedam SB, Lee JJ, et al. Phase II clinical trial of ixabepilone (BMS-247550), an epothilone B analog, in metastatic and locally advanced breast cancer. J Clin Oncol 2005; 23:2726.
  48. Martín M, Lluch A, Casado A, et al. Clinical activity of chronic oral etoposide in previously treated metastatic breast cancer. J Clin Oncol 1994; 12:986.
  49. Pusztai L, Walters RS, Valero V, et al. Daily oral etoposide in patients with heavily pretreated metastatic breast cancer. Am J Clin Oncol 1998; 21:442.
  50. Saphner T, Weller EA, Tormey DC, et al. 21-day oral etoposide for metastatic breast cancer: a phase II study and review of the literature. Am J Clin Oncol 2000; 23:258.
  51. Isakoff SJ. Triple-negative breast cancer: role of specific chemotherapy agents. Cancer J 2010; 16:53.
  52. Hortobagyi GN, Bodey GP, Buzdar AU, et al. Evaluation of high-dose versus standard FAC chemotherapy for advanced breast cancer in protected environment units: a prospective randomized study. J Clin Oncol 1987; 5:354.
  53. Falkson G, Tormey DC, Carey P, et al. Long-term survival of patients treated with combination chemotherapy for metastatic breast cancer. Eur J Cancer 1991; 27:973.
  54. 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.
  55. Blomqvist C, Elomaa I, Rissanen P, et al. Influence of treatment schedule on toxicity and efficacy of cyclophosphamide, epirubicin, and fluorouracil in metastatic breast cancer: a randomized trial comparing weekly and every-4-week administration. J Clin Oncol 1993; 11:467.
  56. A prospective randomized trial comparing epirubicin monochemotherapy to two fluorouracil, cyclophosphamide, and epirubicin regimens differing in epirubicin dose in advanced breast cancer patients. The French Epirubicin Study Group. J Clin Oncol 1991; 9:305.
  57. Nabholtz JM, Falkson C, Campos D, et al. Docetaxel and doxorubicin compared with doxorubicin and cyclophosphamide as first-line chemotherapy for metastatic breast cancer: results of a randomized, multicenter, phase III trial. J Clin Oncol 2003; 21:968.
  58. Biganzoli L, Cufer T, Bruning P, et al. Doxorubicin and paclitaxel versus doxorubicin and cyclophosphamide as first-line chemotherapy in metastatic breast cancer: The European Organization for Research and Treatment of Cancer 10961 Multicenter Phase III Trial. J Clin Oncol 2002; 20:3114.
  59. Nabholtz JM, Mackey JR, Smylie M, et al. Phase II study of docetaxel, doxorubicin, and cyclophosphamide as first-line chemotherapy for metastatic breast cancer. J Clin Oncol 2001; 19:314.
  60. Cassier PA, Chabaud S, Trillet-Lenoir V, et al. A phase-III trial of doxorubicin and docetaxel versus doxorubicin and paclitaxel in metastatic breast cancer: results of the ERASME 3 study. Breast Cancer Res Treat 2008; 109:343.
  61. Albain KS, Nag SM, Calderillo-Ruiz G, et al. Gemcitabine plus Paclitaxel versus Paclitaxel monotherapy in patients with metastatic breast cancer and prior anthracycline treatment. J Clin Oncol 2008; 26:3950.
  62. Chan S, Romieu G, Huober J, et al. Phase III study of gemcitabine plus docetaxel compared with capecitabine plus docetaxel for anthracycline-pretreated patients with metastatic breast cancer. J Clin Oncol 2009; 27:1753.
  63. O'Shaughnessy J, Miles D, Vukelja S, et al. Superior survival with capecitabine plus docetaxel combination therapy in anthracycline-pretreated patients with advanced breast cancer: phase III trial results. J Clin Oncol 2002; 20:2812.
  64. Soto C, Torrecillas L, Reyes S, et al. Capecitabine (X) and taxanes in patients with anthracycline-pretreated metastatic breast cancer: sequential vs. combined therapy results from a MOSG randomized phase III trial (abstract). J Clin Oncol 2006; 24:20s.
  65. Thomas ES, Gomez HL, Li RK, et al. Ixabepilone plus capecitabine for metastatic breast cancer progressing after anthracycline and taxane treatment. J Clin Oncol 2007; 25:5210.
  66. Stockler MR, Harvey VJ, Francis PA, et al. Capecitabine versus classical cyclophosphamide, methotrexate, and fluorouracil as first-line chemotherapy for advanced breast cancer. J Clin Oncol 2011; 29:4498.
  67. Carrick S, Ghersi D, Wilcken N, Simes J. Platinum containing regimens for metastatic breast cancer. Cochrane Database Syst Rev 2004; :CD003374.
  68. Berry DA, Ueno NT, Johnson MM, et al. High-dose chemotherapy with autologous hematopoietic stem-cell transplantation in metastatic breast cancer: overview of six randomized trials. J Clin Oncol 2011; 29:3224.
  69. Gennari A, Stockler M, Puntoni M, et al. Duration of chemotherapy for metastatic breast cancer: a systematic review and meta-analysis of randomized clinical trials. J Clin Oncol 2011; 29:2144.
  70. Park YH, Jung KH, Im SA, et al. Phase III, multicenter, randomized trial of maintenance chemotherapy versus observation in patients with metastatic breast cancer after achieving disease control with six cycles of gemcitabine plus paclitaxel as first-line chemotherapy: KCSG-BR07-02. J Clin Oncol 2013; 31:1732.
  71. Seidman AD. The search for an elusive uniform strategy for a heterogeneous disease: lesson learned? J Clin Oncol 2013; 31:1707.
  72. Eisenhauer EA, Therasse P, Bogaerts J, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer 2009; 45:228.