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Systemic treatment for metastatic breast cancer: General principles

INTRODUCTION

Although metastatic breast cancer is unlikely to be cured, meaningful improvements in survival have been seen, coincident with the introduction of newer systemic therapies [1-3]. Median overall survival (OS) approaches two years, with a range from a few months to many years [4].

The selection of a therapeutic strategy depends upon both tumor biology and clinical factors, with the goal being a tailored approach. Although a subset of patients with oligometastatic disease may benefit from an intensified locoregional approach, most patients with metastatic breast cancer receive systemic medical therapy consisting of chemotherapy, endocrine therapy, and/or biologic therapies, and supportive care measures [5,6].

General principles of management of metastatic breast cancer are presented here. Details of single agent and combination chemotherapy, endocrine therapy, biologic therapy, and how to select among them, as well as locoregional approaches, osteoclast inhibitors (bisphosphonates and receptor activator of nuclear factor kappa-B [RANK] ligand inhibitors), and supportive care, are discussed separately.

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

(See "Systemic treatment of metastatic breast cancer in women: Chemotherapy".)

                                  

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Literature review current through: Mar 2014. | This topic last updated: Mar 4, 2014.
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References
Top
  1. 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.
  2. 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.
  3. 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.
  4. Greenberg PA, Hortobagyi GN, Smith TL, et al. Long-term follow-up of patients with complete remission following combination chemotherapy for metastatic breast cancer. J Clin Oncol 1996; 14:2197.
  5. Pagani O, Senkus E, Wood W, et al. International guidelines for management of metastatic breast cancer: can metastatic breast cancer be cured? J Natl Cancer Inst 2010; 102:456.
  6. Beslija S, Bonneterre J, Burstein HJ, et al. Third consensus on medical treatment of metastatic breast cancer. Ann Oncol 2009; 20:1771.
  7. Stockler M, Wilcken NR, Ghersi D, Simes RJ. Systematic reviews of chemotherapy and endocrine therapy in metastatic breast cancer. Cancer Treat Rev 2000; 26:151.
  8. Osoba D. Health-related quality of life as a treatment endpoint in metastatic breast cancer. Can J Oncol 1995; 5 Suppl 1:47.
  9. Geels P, Eisenhauer E, Bezjak A, et al. Palliative effect of chemotherapy: objective tumor response is associated with symptom improvement in patients with metastatic breast cancer. J Clin Oncol 2000; 18:2395.
  10. Kiely BE, Soon YY, Tattersall MH, Stockler MR. How long have I got? Estimating typical, best-case, and worst-case scenarios for patients starting first-line chemotherapy for metastatic breast cancer: a systematic review of recent randomized trials. J Clin Oncol 2011; 29:456.
  11. Giordano SH, Buzdar AU, Smith TL, et al. Is breast cancer survival improving? Cancer 2004; 100:44.
  12. Mauri D, Polyzos NP, Salanti G, et al. Multiple-treatments meta-analysis of chemotherapy and targeted therapies in advanced breast cancer. J Natl Cancer Inst 2008; 100:1780.
  13. Dawood S, Broglio K, Buzdar AU, et al. Prognosis of women with metastatic breast cancer by HER2 status and trastuzumab treatment: an institutional-based review. J Clin Oncol 2010; 28:92.
  14. Burzykowski T, Buyse M, Piccart-Gebhart MJ, et al. Evaluation of tumor response, disease control, progression-free survival, and time to progression as potential surrogate end points in metastatic breast cancer. J Clin Oncol 2008; 26:1987.
  15. Ahmann DL, Schaid DJ, Bisel HF, et al. The effect on survival of initial chemotherapy in advanced breast cancer: polychemotherapy versus single drug. J Clin Oncol 1987; 5:1928.
  16. Bruzzi P, Del Mastro L, Sormani MP, et al. Objective response to chemotherapy as a potential surrogate end point of survival in metastatic breast cancer patients. J Clin Oncol 2005; 23:5117.
  17. Robertson JF, Howell A, Buzdar A, et al. Static disease on anastrozole provides similar benefit as objective response in patients with advanced breast cancer. Breast Cancer Res Treat 1999; 58:157.
  18. Simmons C, Miller N, Geddie W, et al. Does confirmatory tumor biopsy alter the management of breast cancer patients with distant metastases? Ann Oncol 2009; 20:1499.
  19. Amir E, Clemons M, Purdie CA, et al. Tissue confirmation of disease recurrence in breast cancer patients: pooled analysis of multi-centre, multi-disciplinary prospective studies. Cancer Treat Rev 2012; 38:708.
  20. de Dueñas EM, Hernández AL, Zotano AG, et al. Prospective evaluation of the conversion rate in the receptor status between primary breast cancer and metastasis: results from the GEICAM 2009-03 ConvertHER study. Breast Cancer Res Treat 2014; 143:507.
  21. Swenerton KD, Legha SS, Smith T, et al. Prognostic factors in metastatic breast cancer treated with combination chemotherapy. Cancer Res 1979; 39:1552.
  22. Hortobagyi GN, Smith TL, Legha SS, et al. Multivariate analysis of prognostic factors in metastatic breast cancer. J Clin Oncol 1983; 1:776.
  23. Clark GM, Sledge GW Jr, Osborne CK, McGuire WL. Survival from first recurrence: relative importance of prognostic factors in 1,015 breast cancer patients. J Clin Oncol 1987; 5:55.
  24. Harris JR, Hellman S. Observations on survival curve analysis with particular reference to breast cancer treatment. Cancer 1986; 57:925.
  25. Robertson JF, Dixon AR, Nicholson RI, et al. Confirmation of a prognostic index for patients with metastatic breast cancer treated by endocrine therapy. Breast Cancer Res Treat 1992; 22:221.
  26. Barrios CH, Sampaio C, Vinholes J, Caponero R. What is the role of chemotherapy in estrogen receptor-positive, advanced breast cancer? Ann Oncol 2009; 20:1157.
  27. Stuart-Harris R, Shadbolt B, Palmqvist C, Chaudri Ross HA. The prognostic significance of single hormone receptor positive metastatic breast cancer: an analysis of three randomised phase III trials of aromatase inhibitors. Breast 2009; 18:351.
  28. Emi Y, Kitamura K, Shikada Y, et al. Metastatic breast cancer with HER2/neu-positive cells tends to have a morbid prognosis. Surgery 2002; 131:S217.
  29. Ismail-Khan R, Bui MM. A review of triple-negative breast cancer. Cancer Control 2010; 17:173.
  30. Yamamoto N, Watanabe T, Katsumata N, et al. Construction and validation of a practical prognostic index for patients with metastatic breast cancer. J Clin Oncol 1998; 16:2401.
  31. Leivonen MK, Kalima TV. Prognostic factors associated with survival after breast cancer recurrence. Acta Oncol 1991; 30:583.
  32. Clark GM, Osborne CK, McGuire WL. Correlations between estrogen receptor, progesterone receptor, and patient characteristics in human breast cancer. J Clin Oncol 1984; 2:1102.
  33. Rubens RD, Hayward JL. Estrogen receptors and response to endocrine therapy and cytotoxic chemotherapy in advanced breast cancer. Cancer 1980; 46:2922.
  34. Osborne CK, Yochmowitz MG, Knight WA 3rd, McGuire WL. The value of estrogen and progesterone receptors in the treatment of breast cancer. Cancer 1980; 46:2884.
  35. Bloom ND, Tobin EH, Schreibman B, Degenshein GA. The role of progesterone receptors in the management of advanced breast cancer. Cancer 1980; 45:2992.
  36. Santen RJ, Manni A, Harvey H, Redmond C. Endocrine treatment of breast cancer in women. Endocr Rev 1990; 11:221.
  37. Epstein RJ. The clinical biology of hormone-responsive breast cancer. Cancer Treat Rev 1988; 15:33.
  38. Levine RM, Lippman ME. Relationship between estrogen-receptor proteins and response to chemotherapy in breast cancer. Cancer Treat Rep 1984; 68:573.
  39. Lippman ME, Allegra JC, Thompson EB, et al. The relation between estrogen receptors and response rate to cytotoxic chemotherapy in metastatic breast cancer. N Engl J Med 1978; 298:1223.
  40. Kiang DT, Frenning DH, Goldman AI, et al. Estrogen receptors and responses to chemotherapy and hormonal therapy in advanced breast cancer. N Engl J Med 1978; 299:1330.
  41. Harris L, Fritsche H, Mennel R, et al. American Society of Clinical Oncology 2007 update of recommendations for the use of tumor markers in breast cancer. J Clin Oncol 2007; 25:5287.
  42. De Laurentiis M, Arpino G, Massarelli E, et al. A meta-analysis on the interaction between HER-2 expression and response to endocrine treatment in advanced breast cancer. Clin Cancer Res 2005; 11:4741.
  43. Ahmann DL, Schaid DJ, Ingle JN, et al. A randomized trial of cyclophosphamide, doxorubicin, and prednisone versus cyclophosphamide, 5-fluorouracil, and prednisone in patients with metastatic breast cancer. Am J Clin Oncol 1991; 14:179.
  44. Valagussa P, Tancini G, Bonadonna G. Salvage treatment of patients suffering relapse after adjuvant CMF chemotherapy. Cancer 1986; 58:1411.
  45. Perez JE, Machiavelli M, Leone BA, et al. Bone-only versus visceral-only metastatic pattern in breast cancer: analysis of 150 patients. A GOCS study. Grupo Oncológico Cooperativo del Sur. Am J Clin Oncol 1990; 13:294.
  46. Falkson G, Gelman R, Falkson CI, et al. Factors predicting for response, time to treatment failure, and survival in women with metastatic breast cancer treated with DAVTH: a prospective Eastern Cooperative Oncology Group study. J Clin Oncol 1991; 9:2153.
  47. Rabinovich M, Vallejo C, Bianco A, et al. Development and validation of prognostic models in metastatic breast cancer: a GOCS study. Oncology 1992; 49:188.
  48. Pronzato P, Bertelli G, Gardin G, et al. Analysis of time to response to chemotherapy in 316 metastatic breast cancer patients. Oncology 1993; 50:460.
  49. Aisner J, Cirrincione C, Perloff M, et al. Combination chemotherapy for metastatic or recurrent carcinoma of the breast--a randomized phase III trial comparing CAF versus VATH versus VATH alternating with CMFVP: Cancer and Leukemia Group B Study 8281. J Clin Oncol 1995; 13:1443.
  50. Rahman ZU, Frye DK, Buzdar AU, et al. Impact of selection process on response rate and long-term survival of potential high-dose chemotherapy candidates treated with standard-dose doxorubicin-containing chemotherapy in patients with metastatic breast cancer. J Clin Oncol 1997; 15:3171.
  51. Rozan S, Vincent-Salomon A, Zafrani B, et al. No significant predictive value of c-erbB-2 or p53 expression regarding sensitivity to primary chemotherapy or radiotherapy in breast cancer. Int J Cancer 1998; 79:27.
  52. Hatschek T, Carstensen J, Fagerberg G, et al. Influence of S-phase fraction on metastatic pattern and post-recurrence survival in a randomized mammography screening trial. Breast Cancer Res Treat 1989; 14:321.
  53. Amadori D, Volpi A, Maltoni R, et al. Cell proliferation as a predictor of response to chemotherapy in metastatic breast cancer: a prospective study. Breast Cancer Res Treat 1997; 43:7.
  54. Mechetner E, Kyshtoobayeva A, Zonis S, et al. Levels of multidrug resistance (MDR1) P-glycoprotein expression by human breast cancer correlate with in vitro resistance to taxol and doxorubicin. Clin Cancer Res 1998; 4:389.
  55. Trock BJ, Leonessa F, Clarke R. Multidrug resistance in breast cancer: a meta-analysis of MDR1/gp170 expression and its possible functional significance. J Natl Cancer Inst 1997; 89:917.
  56. Clahsen PC, van de Velde CJ, Duval C, et al. p53 protein accumulation and response to adjuvant chemotherapy in premenopausal women with node-negative early breast cancer. J Clin Oncol 1998; 16:470.
  57. Formenti SC, Dunnington G, Uzieli B, et al. Original p53 status predicts for pathological response in locally advanced breast cancer patients treated preoperatively with continuous infusion 5-fluorouracil and radiation therapy. Int J Radiat Oncol Biol Phys 1997; 39:1059.
  58. Weisenthal LM, Kern DH. Prediction of drug resistance in cancer chemotherapy: the Kern and DiSC assays. Oncology (Williston Park) 1991; 5:93.
  59. Tavassoli FA, Cook CB, Pestaner JP. A comparison of two commercially available in vitro chemosensitivity assays. Oncology 1995; 52:413.
  60. Elledge RM, Clark GM, Hon J, et al. Rapid in vitro assay for predicting response to fluorouracil in patients with metastatic breast cancer. J Clin Oncol 1995; 13:419.
  61. Samson DJ, Seidenfeld J, Ziegler K, Aronson N. Chemotherapy sensitivity and resistance assays: a systematic review. J Clin Oncol 2004; 22:3618.
  62. Schrag D, Garewal HS, Burstein HJ, et al. American Society of Clinical Oncology Technology Assessment: chemotherapy sensitivity and resistance assays. J Clin Oncol 2004; 22:3631.
  63. Wilcken N, Hornbuckle J, Ghersi D. Chemotherapy alone versus endocrine therapy alone for metastatic breast cancer. Cochrane Database Syst Rev 2003; :CD002747.
  64. Taylor SG 4th, Gelman RS, Falkson G, Cummings FJ. Combination chemotherapy compared to tamoxifen as initial therapy for stage IV breast cancer in elderly women. Ann Intern Med 1986; 104:455.
  65. A randomized trial in postmenopausal patients with advanced breast cancer comparing endocrine and cytotoxic therapy given sequentially or in combination. The Australian and New Zealand Breast Cancer Trials Group, Clinical Oncological Society of Australia. J Clin Oncol 1986; 4:186.
  66. 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.
  67. Coates A, Gebski V, Bishop JF, et al. Improving the quality of life during chemotherapy for advanced breast cancer. A comparison of intermittent and continuous treatment strategies. N Engl J Med 1987; 317:1490.
  68. Muss HB, Case LD, Richards F 2nd, et al. Interrupted versus continuous chemotherapy in patients with metastatic breast cancer. The Piedmont Oncology Association. N Engl J Med 1991; 325:1342.
  69. Cheung KL, Evans AJ, Robertson JF. The use of blood tumour markers in the monitoring of metastatic breast cancer unassessable for response to systemic therapy. Breast Cancer Res Treat 2001; 67:273.
  70. Robertson JF, Whynes DK, Dixon A, Blamey RW. Potential for cost economies in guiding therapy in patients with metastatic breast cancer. Br J Cancer 1995; 72:174.
  71. Stearns V, Yamauchi H, Hayes DF. Circulating tumor markers in breast cancer: accepted utilities and novel prospects. Breast Cancer Res Treat 1998; 52:239.
  72. Kiang DT, Greenberg LJ, Kennedy BJ. Tumor marker kinetics in the monitoring of breast cancer. Cancer 1990; 65:193.
  73. Symeonidis A, Kouraklis-Symeonidis A, Apostolopoulos D, et al. Increased serum CA-15.3 levels in patients with megaloblastic anemia due to vitamin B12 deficiency. Oncology 2004; 67:359.
  74. Symeonidis A, Kouraklis-Symeonidis A, Constantinidou I, et al. Increased CA-15.3 levels in the serum of patients with homozygous beta-thalassaemia and sickle cell/beta-thalassaemia. Br J Haematol 2006; 133:692.
  75. Boga C, Ozdogu H, Sezgin N, et al. Serum cancer antigen 15-3 concentrations in patients with sickle cell disease. Br J Haematol 2006; 134:546.
  76. Janicek MJ, Hayes DF, Kaplan WD. Healing flare in skeletal metastases from breast cancer. Radiology 1994; 192:201.
  77. Vogel CL, Schoenfelder J, Shemano I, et al. Worsening bone scan in the evaluation of antitumor response during hormonal therapy of breast cancer. J Clin Oncol 1995; 13:1123.
  78. Ben-Haim S, Israel O. Breast cancer: role of SPECT and PET in imaging bone metastases. Semin Nucl Med 2009; 39:408.
  79. Constantinidou A, Martin A, Sharma B, Johnston SR. Positron emission tomography/computed tomography in the management of recurrent/metastatic breast cancer: a large retrospective study from the Royal Marsden Hospital. Ann Oncol 2011; 22:307.
  80. Rosen EL, Eubank WB, Mankoff DA. FDG PET, PET/CT, and breast cancer imaging. Radiographics 2007; 27 Suppl 1:S215.
  81. Stafford SE, Gralow JR, Schubert EK, et al. Use of serial FDG PET to measure the response of bone-dominant breast cancer to therapy. Acad Radiol 2002; 9:913.
  82. Tateishi U, Gamez C, Dawood S, et al. Bone metastases in patients with metastatic breast cancer: morphologic and metabolic monitoring of response to systemic therapy with integrated PET/CT. Radiology 2008; 247:189.
  83. Specht JM, Tam SL, Kurland BF, et al. Serial 2-[18F] fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) to monitor treatment of bone-dominant metastatic breast cancer predicts time to progression (TTP). Breast Cancer Res Treat 2007; 105:87.
  84. Weigelt B, Bosma AJ, Hart AA, et al. Marker genes for circulating tumour cells predict survival in metastasized breast cancer patients. Br J Cancer 2003; 88:1091.
  85. Cristofanilli M, Budd GT, Ellis MJ, et al. Circulating tumor cells, disease progression, and survival in metastatic breast cancer. N Engl J Med 2004; 351:781.
  86. Cristofanilli M, Hayes DF, Budd GT, et al. Circulating tumor cells: a novel prognostic factor for newly diagnosed metastatic breast cancer. J Clin Oncol 2005; 23:1420.
  87. Hayes DF, Cristofanilli M, Budd GT, et al. Circulating tumor cells at each follow-up time point during therapy of metastatic breast cancer patients predict progression-free and overall survival. Clin Cancer Res 2006; 12:4218.
  88. Wong NS, Kahn HJ, Zhang L, et al. Prognostic significance of circulating tumour cells enumerated after filtration enrichment in early and metastatic breast cancer patients. Breast Cancer Res Treat 2006; 99:63.
  89. Dawood S, Broglio K, Valero V, et al. Circulating tumor cells in metastatic breast cancer: from prognostic stratification to modification of the staging system? Cancer 2008; 113:2422.
  90. Budd GT, Cristofanilli M, Ellis MJ, et al. Circulating tumor cells versus imaging--predicting overall survival in metastatic breast cancer. Clin Cancer Res 2006; 12:6403.
  91. Liu MC, Shields PG, Warren RD, et al. Circulating tumor cells: a useful predictor of treatment efficacy in metastatic breast cancer. J Clin Oncol 2009; 27:5153.
  92. Information on SWOG trial 0500 available online at http://clinicaltrials.gov/ct2/show/NCT00382018 (Accessed on April 28, 2011).
  93. Olson CE, Ansfield FJ, Richards MJ, et al. Review of local soft tissue recurrence of breast cancer irradiated with and without actinomycin-D. Cancer 1977; 39:1981.
  94. Aebi S, Gelber S, Anderson SJ, et al. Chemotherapy for isolated locoregional recurrence of breast cancer (CALOR): a randomised trial. Lancet Oncol 2014; 15:156.
  95. Pivot X. Adjuvant chemotherapy for local relapse breast cancer. Lancet Oncol 2014; 15:125.
  96. Waeber M, Castiglione-Gertsch M, Dietrich D, et al. Adjuvant therapy after excision and radiation of isolated postmastectomy locoregional breast cancer recurrence: definitive results of a phase III randomized trial (SAKK 23/82) comparing tamoxifen with observation. Ann Oncol 2003; 14:1215.
  97. 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.