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Metastatic Breast Cancer

  • Berta Sousa
  • Joana M. Ribeiro
  • Domen Ribnikar
  • Fátima CardosoEmail author
Chapter

Abstract

This chapter is a review of the current evidence for managing metastatic breast cancer. The treatment of metastatic disease is a complex one when compared to the early setting for which there is clear and high level of evidence. There has been a constant effort to improve survival in metastatic patients, but the incurable nature of the disease, its heterogeneity in terms of presentation and biology, the lack of well-designed clinical trials and the lack of acceptable endpoints have render it difficult. The fast introduction of new drugs makes the comparative standard arms used in most trials outdated, being difficult to generalise their results. A better understanding of the biology of disease is driving the development of new targeted agents as well as new methodologies for diagnosis and assessment of metastatic disease. This is shaping the design of new clinical trials in the metastatic setting with the aim of increasing the efficacy and tolerability of treatments. It is also an important goal in research how to best assess the psychosocial impact of this disease in patients and relatives life as well as the development of specific tools to measure quality of life in advance cancer.

Keywords

Breast cancer Metastatic disease Chemotherapy Fulvestrant Aromatase inhibitors Tamoxifen Everolimus Palbociclib Trastuzumab T-DM1 Pertuzumab 

References

  1. 1.
    International Agency for Research on Cancer. Breast Cancer estimate incidence mapwiAfhgifPfsca.Google Scholar
  2. 2.
  3. 3.
    Society. AC. Breast cancer facts and figures 2003–2004. Atlanta, GA: American Cancer Society; 2003.Google Scholar
  4. 4.
    Institute NC. SEER stat fact sheets: breast cancer. http://seer.cancer.gov/statfacts/html/breast.html. Accessed 31 July 2015.
  5. 5.
    Amir E, Clemons M, Purdie CA, Miller N, Quinlan P, Geddie W, 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(6):708–14.PubMedCrossRefGoogle Scholar
  6. 6.
    Osborne CK. Tamoxifen in the treatment of breast cancer. N Engl J Med. 1998;339(22):1609–18.PubMedCrossRefGoogle Scholar
  7. 7.
    Dawood S, Broglio K, Buzdar AU, Hortobagyi GN, Giordano SH. Prognosis of women with metastatic breast cancer by HER2 status and trastuzumab treatment: an institutional-based review. J Clin Oncol (Official Journal of the American Society of Clinical Oncology). 2010;28(1):92–8.CrossRefGoogle Scholar
  8. 8.
    Characterization of metastatic breast cancer (mBC): and ancillary study of the SAFIR01 & MOSCATO trials [abstract]. Ann. Oncol. 25 aO.Google Scholar
  9. 9.
    Toy W, Shen Y, Won H, Green B, Sakr RA, Will M, et al. ESR1 ligand-binding domain mutations in hormone-resistant breast cancer. Nat Genet. 2013;45(12):1439–45.PubMedPubMedCentralCrossRefGoogle Scholar
  10. 10.
    Massard C. Enriching phase I trials with molecular alterations: interim analysis of 708 patients enrolled in the MOSCATO 01 trial [abstract]. In: 13th international congress on targeted anticancer therapies, Paris, France, aO3.7 (2015).Google Scholar
  11. 11.
    Bidard FC, Peeters DJ, Fehm T, Nole F, Gisbert-Criado R, Mavroudis D, et al. Clinical validity of circulating tumour cells in patients with metastatic breast cancer: a pooled analysis of individual patient data. Lancet Oncol. 2014;15(4):406–14.PubMedCrossRefGoogle Scholar
  12. 12.
    Hayes DF, Cristofanilli M, Budd GT, Ellis MJ, Stopeck A, Miller MC, 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 (An Official Journal of the American Association for Cancer Research). 2006;12(14 Pt 1):4218–24.CrossRefGoogle Scholar
  13. 13.
    Smerage JB, Barlow WE, Hortobagyi GN, Winer EP, Leyland-Jones B, Srkalovic G, et al. Circulating tumor cells and response to chemotherapy in metastatic breast cancer: SWOG S0500. J Clin Oncol (Official Journal of the American Society of Clinical Oncology). 2014;32(31):3483–9.CrossRefGoogle Scholar
  14. 14.
    Amir E, Miller N, Geddie W, Freedman O, Kassam F, Simmons C, et al. Prospective study evaluating the impact of tissue confirmation of metastatic disease in patients with breast cancer. J Clin Oncol (Official Journal of the American Society of Clinical Oncology). 2012;30(6):587–92.CrossRefGoogle Scholar
  15. 15.
    Cardoso F, Costa A, Norton L, Cameron D, Cufer T, Fallowfield L, et al. 1st international consensus guidelines for advanced breast cancer (ABC 1). Breast. 2012;21(3):242–52.PubMedCrossRefGoogle Scholar
  16. 16.
    Cardoso F, Costa A, Norton L, Senkus E, Aapro M, Andre F, et al. ESO-ESMO 2nd international consensus guidelines for advanced breast cancer (ABC2)dagger. Ann Oncol (Official Journal of the European Society for Medical Oncology)/ESMO. 2014;25(10):1871–88.CrossRefGoogle Scholar
  17. 17.
    Van Poznak C, Somerfield MR, Bast RC, Cristofanilli M, Goetz MP, Gonzalez-Angulo AM, et al. Use of biomarkers to guide decisions on systemic therapy for women with metastatic breast cancer: american society of clinical oncology clinical practice guideline. J Clin Oncol (Official Journal of the American Society of Clinical Oncology). 2015;33(24):2695–704.CrossRefGoogle Scholar
  18. 18.
    Dawson SJ, Tsui DW, Murtaza M, Biggs H, Rueda OM, Chin SF, et al. Analysis of circulating tumor DNA to monitor metastatic breast cancer. N Engl J Med. 2013;368(13):1199–209.PubMedCrossRefGoogle Scholar
  19. 19.
    Janku F, Wheler JJ, Westin SN, Moulder SL, Naing A, Tsimberidou AM, et al. PI3K/AKT/mTOR inhibitors in patients with breast and gynecologic malignancies harboring PIK3CA mutations. J Clin Oncol (Official Journal of the American Society of Clinical Oncology). 2012;30(8):777–82.CrossRefGoogle Scholar
  20. 20.
    Andre F, Bachelot T, Campone M, Dalenc F, Perez-Garcia JM, Hurvitz SA, et al. Targeting FGFR with dovitinib (TKI258): preclinical and clinical data in breast cancer. Clin Cancer Res. 2013;19(13):3693–702.PubMedCrossRefGoogle Scholar
  21. 21.
    Andre F, Bachelot T, Commo F, Campone M, Arnedos M, Dieras V, et al. Comparative genomic hybridisation array and DNA sequencing to direct treatment of metastatic breast cancer: a multicentre, prospective trial (SAFIR01/UNICANCER). Lancet Oncol. 2014;15(3):267–74.PubMedCrossRefGoogle Scholar
  22. 22.
    Dickler M. A first-in-human phase I study to evaluate the oral selective oestrogen receptor degrader GDC-0810 (ARN-810) in postmenopausal women with oestrogen receptor+ HER2–, advanced/metastatic breast cancer. AACR [abstract CT231] (2015).Google Scholar
  23. 23.
    Arnedos M. Genomic and immune characterization of metastatic breast cancer (mBC): and ancillary study of the SAFIR01 & MOSCATO trials [abstract]. Ann Oncol. 2014;25:a351O.CrossRefGoogle Scholar
  24. 24.
    Niikura N, Costelloe CM, Madewell JE, Hayashi N, Yu TK, Liu J, et al. FDG-PET/CT compared with conventional imaging in the detection of distant metastases of primary breast cancer. Oncologist. 2011;16(8):1111–9.PubMedPubMedCentralCrossRefGoogle Scholar
  25. 25.
    Nakai T, Okuyama C, Kubota T, Yamada K, Ushijima Y, Taniike K, et al. Pitfalls of FDG-PET for the diagnosis of osteoblastic bone metastases in patients with breast cancer. Eur J Nucl Med Mol Imaging. 2005;32(11):1253–8.PubMedCrossRefGoogle Scholar
  26. 26.
    Janicek MJ, Hayes DF, Kaplan WD. Healing flare in skeletal metastases from breast cancer. Radiology. 1994;192(1):201–4.PubMedCrossRefGoogle Scholar
  27. 27.
    Fiteni F, Villanueva C, Bazan F, Perrin S, Chaigneau L, Dobi E, et al. Long-term follow-up of patients with metastatic breast cancer treated by trastuzumab: impact of institutions. Breast. 2014;23(2):165–9.PubMedCrossRefGoogle Scholar
  28. 28.
    Relevance of breast cancer hormone receptors and other factors to the efficacy of adjuvant tamoxifen: patient-level meta-analysis of randomised trials. Lancet. 2011;378(9793):771–84.Google Scholar
  29. 29.
    Slamon DJ, Leyland-Jones B, Shak S, Fuchs H, Paton V, Bajamonde A, et al. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med. 2001;344(11):783–92.PubMedCrossRefGoogle Scholar
  30. 30.
    Rabinovich M, Vallejo C, Bianco A, Perez J, Machiavelli M, Leone B, et al. Development and validation of prognostic models in metastatic breast cancer: a GOCS study. Oncology. 1992;49(3):188–95.PubMedCrossRefGoogle Scholar
  31. 31.
    Rahman ZU, Frye DK, Buzdar AU, Smith TL, Asmar L, Champlin RE, 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 (Official Journal of the American Society of Clinical Oncology). 1997;15(10):3171–7.CrossRefGoogle Scholar
  32. 32.
    Yamamoto N, Watanabe T, Katsumata N, Omuro Y, Ando M, Fukuda H, et al. Construction and validation of a practical prognostic index for patients with metastatic breast cancer. J Clin Oncol (Official Journal of the American Society of Clinical Oncology). 1998;16(7):2401–8.CrossRefGoogle Scholar
  33. 33.
    Hortobagyi GN, Smith TL, Legha SS, Swenerton KD, Gehan EA, Yap HY, et al. Multivariate analysis of prognostic factors in metastatic breast cancer. J Clin Oncol (Official Journal of the American Society of Clinical Oncology). 1983;1(12):776–86.CrossRefGoogle Scholar
  34. 34.
    Regierer AC, Wolters R, Ufen MP, Weigel A, Novopashenny I, Kohne CH, et al. An internally and externally validated prognostic score for metastatic breast cancer: analysis of 2269 patients. Ann Oncol (Official Journal of the European Society for Medical Oncology)/ESMO. 2014;25(3):633–8.CrossRefGoogle Scholar
  35. 35.
    Biganzoli L, Wildiers H, Oakman C, Marotti L, Loibl S, Kunkler I, et al. Management of elderly patients with breast cancer: updated recommendations of the International Society of Geriatric Oncology (SIOG) and European Society of Breast Cancer Specialists (EUSOMA). Lancet Oncol. 2012;13(4):e148–60.PubMedCrossRefGoogle Scholar
  36. 36.
    Perou CM, Sorlie T, Eisen MB, van de Rijn M, Jeffrey SS, Rees CA, et al. Molecular portraits of human breast tumours. Nature. 2000;406(6797):747–52.PubMedCrossRefGoogle Scholar
  37. 37.
    Weigelt B, Hu Z, He X, Livasy C, Carey LA, Ewend MG, et al. Molecular portraits and 70-gene prognosis signature are preserved throughout the metastatic process of breast cancer. Cancer Res. 2005;65(20):9155–8.PubMedCrossRefGoogle Scholar
  38. 38.
    Sanchez-Martinez C, Gelbert LM, Lallena MJ, de Dios A. Cyclin dependent kinase (CDK) inhibitors as anticancer drugs. Bioorg Med Chem Lett. 2015;25(17):3420–35.PubMedCrossRefGoogle Scholar
  39. 39.
    Wilcken N, Hornbuckle J, Ghersi D. Chemotherapy alone versus endocrine therapy alone for metastatic breast cancer. Cochrane Database Syst Rev. 2003;2:CD002747.Google Scholar
  40. 40.
    Largillier R, Ferrero JM, Doyen J, Barriere J, Namer M, Mari V, et al. Prognostic factors in 1038 women with metastatic breast cancer. Ann Oncol (Official Journal of the European Society for Medical Oncology)/ESMO. 2008;19(12):2012–9.CrossRefGoogle Scholar
  41. 41.
    Amadori D, Volpi A, Maltoni R, Nanni O, Amaducci L, Amadori A, et al. Cell proliferation as a predictor of response to chemotherapy in metastatic breast cancer: a prospective study. Breast Cancer Res Treat. 1997;43(1):7–14.PubMedCrossRefGoogle Scholar
  42. 42.
    Hatschek T, Carstensen J, Fagerberg G, Stal O, Grontoft O, Nordenskjold B. Influence of S-phase fraction on metastatic pattern and post-recurrence survival in a randomized mammography screening trial. Breast Cancer Res Treat. 1989;14(3):321–7.PubMedCrossRefGoogle Scholar
  43. 43.
    Schrag D, Garewal HS, Burstein HJ, Samson DJ, Von Hoff DD, Somerfield MR, et al. American Society of Clinical Oncology Technology Assessment: chemotherapy sensitivity and resistance assays. J Clin Oncol (Official Journal of the American Society of Clinical Oncology). 2004;22(17):3631–8.CrossRefGoogle Scholar
  44. 44.
    Ignatiadis M, Sotiriou C. Luminal breast cancer: from biology to treatment. Nat Rev Clin Oncol. 2013;10(9):494–506.PubMedCrossRefGoogle Scholar
  45. 45.
    Early Breast Cancer Trialists’ Collaborative G. 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(9472):1687–717.CrossRefGoogle Scholar
  46. 46.
    Clarke R, Tyson JJ, Dixon JM. Endocrine resistance in breast cancer—an overview and update. Mol Cell Endocrinol. 2015;418(Pt 3):220–34.PubMedPubMedCentralCrossRefGoogle Scholar
  47. 47.
    Jeselsohn R, Buchwalter G, De Angelis C, Brown M, Schiff R. ESR1 mutations-a mechanism for acquired endocrine resistance in breast cancer. Nat Rev Clin Oncol. 2015;12(10):573–83.PubMedPubMedCentralCrossRefGoogle Scholar
  48. 48.
    Nardone A, De Angelis C, Trivedi MV, Osborne CK, Schiff R. The changing role of ER in endocrine resistance. Breast. 2015;24(Suppl 2):S60–6.PubMedPubMedCentralCrossRefGoogle Scholar
  49. 49.
    Ciruelos Gil EM. Targeting the PI3 K/AKT/mTOR pathway in estrogen receptor-positive breast cancer. Cancer Treat Rev. 2014;40(7):862–71.PubMedCrossRefGoogle Scholar
  50. 50.
    Butt AJ, McNeil CM, Musgrove EA, Sutherland RL. Downstream targets of growth factor and oestrogen signalling and endocrine resistance: the potential roles of c-Myc, cyclin D1 and cyclin E. Endocr Relat Cancer. 2005;12(Suppl 1):S47–59.PubMedCrossRefGoogle Scholar
  51. 51.
    Caldon CE, Daly RJ, Sutherland RL, Musgrove EA. Cell cycle control in breast cancer cells. J Cell Biochem. 2006;97(2):261–74.PubMedCrossRefGoogle Scholar
  52. 52.
    Miller TE, Ghoshal K, Ramaswamy B, Roy S, Datta J, Shapiro CL, et al. MicroRNA-221/222 confers tamoxifen resistance in breast cancer by targeting p27Kip1. J Biol Chem. 2008;283(44):29897–903.PubMedPubMedCentralCrossRefGoogle Scholar
  53. 53.
    Litherland S, Jackson IM. Antioestrogens in the management of hormone-dependent cancer. Cancer Treat Rev. 1988;15(3):183–94.PubMedCrossRefGoogle Scholar
  54. 54.
    Baum M, Budzar AU, Cuzick J, Forbes J, Houghton JH, Klijn JG, et al. Anastrozole alone or in combination with tamoxifen versus tamoxifen alone for adjuvant treatment of postmenopausal women with early breast cancer: first results of the ATAC randomised trial. Lancet. 2002;359(9324):2131–9.PubMedCrossRefGoogle Scholar
  55. 55.
    Mauri D, Pavlidis N, Polyzos NP, Ioannidis JP. Survival with aromatase inhibitors and inactivators versus standard hormonal therapy in advanced breast cancer: meta-analysis. J Natl Cancer Inst. 2006;98(18):1285–91.PubMedCrossRefGoogle Scholar
  56. 56.
    Rose C, Vtoraya O, Pluzanska A, Davidson N, Gershanovich M, Thomas R, et al. An open randomised trial of second-line endocrine therapy in advanced breast cancer. Comparison of the aromatase inhibitors letrozole and anastrozole. Eur J Cancer. 2003;39(16):2318–27.PubMedCrossRefGoogle Scholar
  57. 57.
    Campos SM, Guastalla JP, Subar M, Abreu P, Winer EP, Cameron DA. A comparative study of exemestane versus anastrozole in patients with postmenopausal breast cancer with visceral metastases. Clin Breast Cancer. 2009;9(1):39–44.PubMedCrossRefGoogle Scholar
  58. 58.
    Dixon JM, Renshaw L, Langridge C, Young OE, McHugh M, Williams L, et al. Anastrozole and letrozole: an investigation and comparison of quality of life and tolerability. Breast Cancer Res Treat. 2011;125(3):741–9.PubMedCrossRefGoogle Scholar
  59. 59.
    Klijn JG, Blamey RW, Boccardo F, Tominaga T, Duchateau L, Sylvester R, et al. Combined tamoxifen and luteinizing hormone-releasing hormone (LHRH) agonist versus LHRH agonist alone in premenopausal advanced breast cancer: a meta-analysis of four randomized trials. J Clin Oncol (Official Journal of the American Society of Clinical Oncology). 2001;19(2):343–53.CrossRefGoogle Scholar
  60. 60.
    Osborne CK, Pippen J, Jones SE, Parker LM, Ellis M, Come S, et al. Double-blind, randomized trial comparing the efficacy and tolerability of fulvestrant versus anastrozole in postmenopausal women with advanced breast cancer progressing on prior endocrine therapy: results of a North American trial. J Clin Oncol (Official Journal of the American Society of Clinical Oncology). 2002;20(16):3386–95.CrossRefGoogle Scholar
  61. 61.
    Chia S, Gradishar W, Mauriac L, Bines J, Amant F, Federico M, et al. Double-blind, randomized placebo controlled trial of fulvestrant compared with exemestane after prior nonsteroidal aromatase inhibitor therapy in postmenopausal women with hormone receptor-positive, advanced breast cancer: results from EFECT. J Clin Oncol (Official Journal of the American Society of Clinical Oncology). 2008;26(10):1664–70.CrossRefGoogle Scholar
  62. 62.
    Al-Mubarak M, Sacher AG, Ocana A, Vera-Badillo F, Seruga B, Amir E. Fulvestrant for advanced breast cancer: a meta-analysis. Cancer Treat Rev. 2013;39(7):753–8.PubMedCrossRefGoogle Scholar
  63. 63.
    Di Leo A, Jerusalem G, Petruzelka L, Torres R, Bondarenko IN, Khasanov R, et al. Final overall survival: fulvestrant 500 mg vesus 250 mg in the randomized CONFIRM trial. J Natl Cancer Inst. 2014;106(1):djt337.Google Scholar
  64. 64.
    Ellis MJ, Llombart-Cussac A, Feltl D, Dewar JA, Jasiowka M, Hewson N, et al. Fulvestrant 500 mg versus anastrozole 1 mg for the first-line treatment of advanced breast cancer: overall survival analysis from the phase II FIRST study. J Clin Oncol (Official Journal of the American Society of Clinical Oncology). 2015;33(32):3781–7.CrossRefGoogle Scholar
  65. 65.
    Bergh J, Jonsson PE, Lidbrink EK, Trudeau M, Eiermann W, Brattstrom D, et al. FACT: an open-label randomized phase III study of fulvestrant and anastrozole in combination compared with anastrozole alone as first-line therapy for patients with receptor-positive postmenopausal breast cancer. J Clin Oncol (Official Journal of the American Society of Clinical Oncology). 2012;30(16):1919–25.CrossRefGoogle Scholar
  66. 66.
    Mehta RS, Barlow WE, Albain KS, Vandenberg TA, Dakhil SR, Tirumali NR, et al. Combination anastrozole and fulvestrant in metastatic breast cancer. N Engl J Med. 2012;367(5):435–44.PubMedPubMedCentralCrossRefGoogle Scholar
  67. 67.
    Johnston SRD, Kilburn LS, Ellis P, Dodwell D, Cameron D, Hayward L, et al. Fulvestrant plus anastrozole or placebo versus exemestane alone after progression on non-steroidal aromatase inhibitors in postmenopausal patients with hormone-receptor-positive locally advanced or metastatic breast cancer (SoFEA): a composite, multicentre, phase 3 randomised trial. Lancet Oncol. 2013;14(10):989–98.PubMedCrossRefGoogle Scholar
  68. 68.
    Cancer Genome Atlas N. Comprehensive molecular portraits of human breast tumours. Nature. 2012;490(7418):61–70.CrossRefGoogle Scholar
  69. 69.
    Boulay A, Rudloff J, Ye J, Zumstein-Mecker S, O’Reilly T, Evans DB, et al. Dual inhibition of mTOR and estrogen receptor signaling in vitro induces cell death in models of breast cancer. Clin Cancer Res (An Official Journal of the American Association for Cancer Research). 2005;11(14):5319–28.CrossRefGoogle Scholar
  70. 70.
    Baselga J, Campone M, Piccart M, Burris HA 3rd, Rugo HS, Sahmoud T, et al. Everolimus in postmenopausal hormone-receptor-positive advanced breast cancer. N Engl J Med. 2012;366(6):520–9.PubMedCrossRefGoogle Scholar
  71. 71.
    Piccart M, Hortobagyi GN, Campone M, Pritchard KI, Lebrun F, Ito Y, et al. Everolimus plus exemestane for hormone-receptor-positive, human epidermal growth factor receptor-2-negative advanced breast cancer: overall survival results from BOLERO-2dagger. Ann Oncol (Official Journal of the European Society for Medical Oncology)/ESMO. 2014;25(12):2357–62.CrossRefGoogle Scholar
  72. 72.
    Wolff AC, Lazar AA, Bondarenko I, Garin AM, Brincat S, Chow L, et al. Randomized phase III placebo-controlled trial of letrozole plus oral temsirolimus as first-line endocrine therapy in postmenopausal women with locally advanced or metastatic breast cancer. J Clin Oncol (Official Journal of the American Society of Clinical Oncology). 2013;31(2):195–202.CrossRefGoogle Scholar
  73. 73.
    Bachelot T, Bourgier C, Cropet C, Ray-Coquard I, Ferrero JM, Freyer G, et al. Randomized phase II trial of everolimus in combination with tamoxifen in patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative metastatic breast cancer with prior exposure to aromatase inhibitors: a GINECO study. J Clin Oncol. 2012;30(22):2718–24.PubMedCrossRefGoogle Scholar
  74. 74.
    Aapro M, Andre F, Blackwell K, Calvo E, Jahanzeb M, Papazisis K, et al. Adverse event management in patients with advanced cancer receiving oral everolimus: focus on breast cancer. Ann Oncol (Official Journal of the European Society for Medical Oncology)/ESMO. 2014;25(4):763–73.CrossRefGoogle Scholar
  75. 75.
    Hortobagyi GN, Chen D, Piccart M, Rugo HS, Burris HA 3rd, Pritchard KI, et al. Correlative analysis of genetic alterations and everolimus benefit in hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer: results from BOLERO-2. J Clin Oncol (Official Journal of the American Society of Clinical Oncology). 2016;34(5):419–26.CrossRefGoogle Scholar
  76. 76.
    Finn RS, Crown JP, Lang I, Boer K, Bondarenko IM, Kulyk SO, et al. The cyclin-dependent kinase 4/6 inhibitor palbociclib in combination with letrozole versus letrozole alone as first-line treatment of oestrogen receptor-positive, HER2-negative, advanced breast cancer (PALOMA-1/TRIO-18): a randomised phase 2 study. Lancet Oncol. 2015;16(1):25–35.PubMedCrossRefGoogle Scholar
  77. 77.
    Turner NC, Huang Bartlett C, Cristofanilli M. Palbociclib in hormone-receptor-positive advanced breast cancer. N Engl J Med. 2015;373(17):1672–3.Google Scholar
  78. 78.
    Turner NC, Ro J, Andre F, Loi S, Verma S, Iwata H, et al. Palbociclib in hormone-receptor-positive advanced breast cancer. N Engl J Med. 2015;373(3):209–19.PubMedCrossRefGoogle Scholar
  79. 79.
    Munster PN, Thurn KT, Thomas S, Raha P, Lacevic M, Miller A, et al. A phase II study of the histone deacetylase inhibitor vorinostat combined with tamoxifen for the treatment of patients with hormone therapy-resistant breast cancer. Br J Cancer. 2011;104(12):1828–35.PubMedPubMedCentralCrossRefGoogle Scholar
  80. 80.
    Baselga J, Im S-A, Iwata H, Clemons M, Ito Y, Awada A, Chia S, Jagiello-Gruszfeld A, Pistilli B, Tseng L-M, Hurvitz S, Masuda N, Cortés J, De Laurentiis M, Arteaga CL, Jiang Z, Jonat W, Hachemi S, Le Mouhaër S, Di Tomaso E, Urban P, Massacesi C, Campone M. PIK3CA status in circulating tumor DNA (ctDNA) predicts efficacy of buparlisib (BUP) plus fulvestrant (FULV) in postmenopausal women with endocrine-resistant HR+/HER2− advanced breast cancer (BC): first results from the randomized, phase III BELLE-2 trial. Abstract S6-01. Presented at: San Antonio Breast Cancer Symposium; 8–12 Dec 2015.Google Scholar
  81. 81.
    Piccart-Gebhart MJ, Burzykowski T, Buyse M, Sledge G, Carmichael J, Luck HJ, et al. Taxanes alone or in combination with anthracyclines as first-line therapy of patients with metastatic breast cancer. J Clin Oncol (Official Journal of the American Society of Clinical Oncology). 2008;26(12):1980–6.CrossRefGoogle Scholar
  82. 82.
    Fumoleau P, Largillier R, Clippe C, Dieras V, Orfeuvre H, Lesimple T, et al. Multicentre, phase II study evaluating capecitabine monotherapy in patients with anthracycline- and taxane-pretreated metastatic breast cancer. Euro J Cancer. 2004;40(4):536–42.CrossRefGoogle Scholar
  83. 83.
    Kaufman PA, Awada A, Twelves C, Yelle L, Perez EA, Velikova G, 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 (Official Journal of the American Society of Clinical Oncology). 2015;33(6):594–601.CrossRefGoogle Scholar
  84. 84.
    Martin M, Ruiz A, Munoz M, Balil A, Garcia-Mata J, Calvo L, 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(3):219–25.PubMedCrossRefGoogle Scholar
  85. 85.
    Cortes J, O’Shaughnessy J, Loesch D, Blum JL, Vahdat LT, Petrakova K, 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(9769):914–23.PubMedCrossRefGoogle Scholar
  86. 86.
    Rha SY, Moon YH, Jeung HC, Kim YT, Sohn JH, Yang WI, et al. Gemcitabine monotherapy as salvage chemotherapy in heavily pretreated metastatic breast cancer. Breast Cancer Res Treat. 2005;90(3):215–21.PubMedCrossRefGoogle Scholar
  87. 87.
    Carrick S, Ghersi D, Wilcken N, Simes J. Platinum containing regimens for metastatic breast cancer. Cochrane Database Syst Rev. 2004;2:CD003374.Google Scholar
  88. 88.
    Stockler MR, Harvey VJ, Francis PA, Byrne MJ, Ackland SP, Fitzharris B, et al. Capecitabine versus classical cyclophosphamide, methotrexate, and fluorouracil as first-line chemotherapy for advanced breast cancer. J Clin Oncol (Official Journal of the American Society of Clinical Oncology). 2011;29(34):4498–504.CrossRefGoogle Scholar
  89. 89.
    O’Brien MER. Reduced cardiotoxicity and comparable efficacy in a phase III trial of pegylated liposomal doxorubicin HCl (CAELYXTM/Doxil”) versus conventional doxorubicin for first-line treatment of metastatic breast cancer. Ann Oncol. 2004;15(3):440–9.PubMedCrossRefGoogle Scholar
  90. 90.
    Cardoso F, Bedard PL, Winer EP, Pagani O, Senkus-Konefka E, Fallowfield LJ, et al. International guidelines for management of metastatic breast cancer: combination vs sequential single-agent chemotherapy. J Natl Cancer Inst. 2009;101(17):1174–81.PubMedPubMedCentralCrossRefGoogle Scholar
  91. 91.
    Slamon DJ, Clark GM, Wong SG, Levin WJ, Ullrich A, McGuire WL. Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science. 1987;235(4785):177–82.PubMedCrossRefGoogle Scholar
  92. 92.
    Browne BC, O’Brien N, Duffy MJ, Crown J, O’Donovan N. HER-2 signaling and inhibition in breast cancer. Curr Cancer Drug Targets. 2009;9(3):419–38.PubMedCrossRefGoogle Scholar
  93. 93.
    Vu T, Claret FX. Trastuzumab: updated mechanisms of action and resistance in breast cancer. Front Oncol. 2012;2:62.PubMedPubMedCentralCrossRefGoogle Scholar
  94. 94.
    Klapper LN, Waterman H, Sela M, Yarden Y. Tumor-inhibitory antibodies to HER-2/ErbB-2 may act by recruiting c-Cbl and enhancing ubiquitination of HER-2. Cancer Res. 2000;60(13):3384–8.PubMedGoogle Scholar
  95. 95.
    Arnould L, Gelly M, Penault-Llorca F, Benoit L, Bonnetain F, Migeon C, et al. Trastuzumab-based treatment of HER2-positive breast cancer: an antibody-dependent cellular cytotoxicity mechanism? Br J Cancer. 2006;94(2):259–67.PubMedPubMedCentralCrossRefGoogle Scholar
  96. 96.
    O’Shaughnessy J, Vukelja SJ, Marsland T, Kimmel G, Ratnam S, Pippen J. Phase II trial of gemcitabine plus trastuzumab in metastatic breast cancer patients previously treated with chemotherapy: preliminary results. Clin Breast Cancer. 2002;3(Suppl 1):17–20.PubMedCrossRefGoogle Scholar
  97. 97.
    Burstein HJ, Keshaviah A, Baron A, et al. Trastuzumab and vinorelbine or taxane chemotherapy for HER2+ metastatic breast cancer: the TRAVIOTA study. J Clin Oncol 2006;24:40s (Abstr 650).Google Scholar
  98. 98.
    Robert N, Leyland-Jones B, Asmar L, Belt R, Ilegbodu D, Loesch D, et al. Randomized phase III study of trastuzumab, paclitaxel, and carboplatin compared with trastuzumab and paclitaxel in women with HER-2-overexpressing metastatic breast cancer. J Clin Oncol (Official Journal of the American Society of Clinical Oncology). 2006;24(18):2786–92.CrossRefGoogle Scholar
  99. 99.
    Seidman AD, Berry D, Cirrincione C, Harris L, Muss H, Marcom PK, 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 (Official Journal of the American Society of Clinical Oncology). 2008;26(10):1642–9.CrossRefGoogle Scholar
  100. 100.
    Andersson M, Lidbrink E, Bjerre K, Wist E, Enevoldsen K, Jensen AB, et al. Phase III randomized study comparing docetaxel plus trastuzumab with vinorelbine plus trastuzumab as first-line therapy of metastatic or locally advanced human epidermal growth factor receptor 2-positive breast cancer: the HERNATA study. J Clin Oncol (Official Journal of the American Society of Clinical Oncology). 2011;29(3):264–71.CrossRefGoogle Scholar
  101. 101.
    Valero V, Forbes J, Pegram MD, Pienkowski T, Eiermann W, von Minckwitz G, et al. Multicenter phase III randomized trial comparing docetaxel and trastuzumab with docetaxel, carboplatin, and trastuzumab as first-line chemotherapy for patients with HER2-gene-amplified metastatic breast cancer (BCIRG 007 study): two highly active therapeutic regimens. J Clin Oncol (Official Journal of the American Society of Clinical Oncology). 2011;29(2):149–56.CrossRefGoogle Scholar
  102. 102.
    Pegram MD, Pienkowski T, Northfelt DW, Eiermann W, Patel R, Fumoleau P, et al. Results of two open-label, multicenter phase II studies of docetaxel, platinum salts, and trastuzumab in HER2-positive advanced breast cancer. J Natl Cancer Inst. 2004;96(10):759–69.PubMedCrossRefGoogle Scholar
  103. 103.
    Perez EA, Suman VJ, Rowland KM, Ingle JN, Salim M, Loprinzi CL, et al. Two concurrent phase II trials of paclitaxel/carboplatin/trastuzumab (weekly or every-3-week schedule) as first-line therapy in women with HER2-overexpressing metastatic breast cancer: NCCTG study 983252. Clin Breast Cancer. 2005;6(5):425–32.PubMedCrossRefGoogle Scholar
  104. 104.
    Wolff AC, Hammond ME, Schwartz JN, Hagerty KL, Allred DC, Cote RJ, et al. American Society of Clinical Oncology/College of American Pathologists guideline recommendations for human epidermal growth factor receptor 2 testing in breast cancer. J Clin Oncol. 2007;25(1):118–45.PubMedCrossRefGoogle Scholar
  105. 105.
    Narayan M, Wilken JA, Harris LN, Baron AT, Kimbler KD, Maihle NJ. Trastuzumab-induced HER reprogramming in “resistant” breast carcinoma cells. Cancer Res. 2009;69(6):2191–4.PubMedCrossRefGoogle Scholar
  106. 106.
    Portera CC, Walshe JM, Rosing DR, Denduluri N, Berman AW, Vatas U, et al. Cardiac toxicity and efficacy of trastuzumab combined with pertuzumab in patients with [corrected] human epidermal growth factor receptor 2-positive metastatic breast cancer. Clin Cancer Res (An Official Journal of the American Association for Cancer Research). 2008;14(9):2710–6.CrossRefGoogle Scholar
  107. 107.
    Scheuer W, Friess T, Burtscher H, Bossenmaier B, Endl J, Hasmann M. Strongly enhanced antitumor activity of trastuzumab and pertuzumab combination treatment on HER2-positive human xenograft tumor models. Cancer Res. 2009;69(24):9330–6.PubMedCrossRefGoogle Scholar
  108. 108.
    Baselga J, Gelmon KA, Verma S, Wardley A, Conte P, Miles D, et al. Phase II trial of pertuzumab and trastuzumab in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer that progressed during prior trastuzumab therapy. J Clin Oncol (Official Journal of the American Society of Clinical Oncology). 2010;28(7):1138–44.CrossRefGoogle Scholar
  109. 109.
    Baselga J, Cortes J, Kim SB, Im SA, Hegg R, Im YH, et al. Pertuzumab plus trastuzumab plus docetaxel for metastatic breast cancer. N Engl J Med. 2012;366(2):109–19.PubMedCrossRefGoogle Scholar
  110. 110.
    Swain SM, Kim S-B, Cortés J, Ro J, Semiglazov V, Campone M, et al. Pertuzumab, trastuzumab, and docetaxel for HER2-positive metastatic breast cancer (CLEOPATRA study): overall survival results from a randomised, double-blind, placebo-controlled, phase 3 study. Lancet Oncol. 2013;14(6):461–71.PubMedPubMedCentralCrossRefGoogle Scholar
  111. 111.
    Baselga J, Swain SM. CLEOPATRA: a phase III evaluation of pertuzumab and trastuzumab for HER2-positive metastatic breast cancer. Clin Breast Cancer. 2010;10(6):489–91.PubMedCrossRefGoogle Scholar
  112. 112.
    Dang C, Iyengar N, Datko F, D’Andrea G, Theodoulou M, Dickler M, et al. Phase II study of paclitaxel given once per week along with trastuzumab and pertuzumab in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer. J Clin Oncol (Official Journal of the American Society of Clinical Oncology). 2015;33(5):442–7.CrossRefGoogle Scholar
  113. 113.
    Perez EA, Lopez-Vega JM, Del Mastro L, Petit T, Mitchell L, Pelizon CH, Andersson M. A combination of pertuzumab, trastuzumab, and vinorelbine for first-line treatment of patients with HER2-positive metastatic breast cancer: An open-label, two-cohort, phase II study (VELVET). J Clin Oncol 2012;30(suppl; abstr TPS653).Google Scholar
  114. 114.
    Ellis PA, Barrios CH, Eiermann W et al. Phase III, randomized study of trastuzumab emtansine (T-DM1)± pertuzumab (P) vs trastuzumab + taxane (HT) for first-line treatment of HER2-positive MBC: primary results from the MARIANNE study. J Clin Oncol 2015;33(suppl; abstr 507).Google Scholar
  115. 115.
    Geyer CE, Forster J, Lindquist D, Chan S, Romieu CG, Pienkowski T, et al. Lapatinib plus capecitabine for HER2-positive advanced breast cancer. N Engl J Med. 2006;355(26):2733–43.PubMedCrossRefGoogle Scholar
  116. 116.
    Cameron D, Casey M, Oliva C, Newstat B, Imwalle B, Geyer CE. Lapatinib plus capecitabine in women with HER-2-positive advanced breast cancer: final survival analysis of a phase III randomized trial. Oncologist. 2010;15(9):924–34.PubMedPubMedCentralCrossRefGoogle Scholar
  117. 117.
    Gelmon KA, Boyle F, Kaufman B, et al. Open-label phase III randomized controlled trial comparing taxane-based chemotherapy with lapatinib or trastuzumab as first-line therapy for women with HER2-positive metastatic breast cancer: Interim analysis of NCIC CTG MA.31/GSK EGF 108919. ASCO Annual Meeting Abstract LBA671; 2012.Google Scholar
  118. 118.
    Pivot X, Manikhas A, Zurawski B, Chmielowska E, Karaszewska B, Allerton R, et al. CEREBEL (EGF111438): a phase III, randomized, open-label study of lapatinib plus capecitabine versus trastuzumab plus capecitabine in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer. J Clin Oncol (Official Journal of the American Society of Clinical Oncology). 2015;33(14):1564–73.CrossRefGoogle Scholar
  119. 119.
    Bachelot T, Romieu G, Campone M, Diéras V, Cropet C, Dalenc F, et al. Lapatinib plus capecitabine in patients with previously untreated brain metastases from HER2-positive metastatic breast cancer (LANDSCAPE): a single-group phase 2 study. Lancet Oncol. 2013;14(1):64–71.PubMedCrossRefGoogle Scholar
  120. 120.
    Verma S, Miles D, Gianni L, Krop IE, Welslau M, Baselga J, et al. Trastuzumab emtansine for HER2-positive advanced breast cancer. N Engl J Med. 2012;367(19):1783–91.PubMedPubMedCentralCrossRefGoogle Scholar
  121. 121.
    Giordano SH, Temin S, Kirshner JJ, Chandarlapaty S, Crews JR, Davidson NE, et al. Systemic therapy for patients with advanced human epidermal growth factor receptor 2-positive breast cancer: American Society of Clinical Oncology clinical practice guideline. J Clin Oncol (Official Journal of the American Society of Clinical Oncology). 2014;32(19):2078–99.CrossRefGoogle Scholar
  122. 122.
    Krop IE, Kim S-B, González-Martín A, LoRusso PM, Ferrero J-M, Smitt M, et al. Trastuzumab emtansine versus treatment of physician’s choice for pretreated HER2-positive advanced breast cancer (TH3RESA): a randomised, open-label, phase 3 trial. Lancet Oncol. 2014;15(7):689–99.PubMedCrossRefGoogle Scholar
  123. 123.
    Wildiers H, Kim S-B, Gonzalez-Martin A, LoRusso PM, Ferrero J-M, Yu R, Smitt M, Krop I. Trastuzumab emtansine improves overall survival versus treatment of physician’s choice in patients with previously treated HER2-positive metastatic breast cancer: final overall survival results from the phase 3 TH3RESA study. SABCS 2015 Abstract S5-05.Google Scholar
  124. 124.
    Blackwell KL, Burstein HJ, Storniolo AM, Rugo HS, Sledge G, Aktan G, et al. Overall survival benefit with lapatinib in combination with trastuzumab for patients with human epidermal growth factor receptor 2-positive metastatic breast cancer: final results from the EGF104900 Study. J Clin Oncol (Official Journal of the American Society of Clinical Oncology). 2012;30(21):2585–92.CrossRefGoogle Scholar
  125. 125.
    Cortes J, Fumoleau P, Bianchi GV, Petrella TM, Gelmon K, Pivot X, et al. Pertuzumab monotherapy after trastuzumab-based treatment and subsequent reintroduction of trastuzumab: activity and tolerability in patients with advanced human epidermal growth factor receptor 2-positive breast cancer. J Clin Oncol (Official Journal of the American Society of Clinical Oncology). 2012;30(14):1594–600.CrossRefGoogle Scholar
  126. 126.
    Kaufman B, Mackey JR, Clemens MR, Bapsy PP, Vaid A, Wardley A, 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 (Official Journal of the American Society of Clinical Oncology). 2009;27(33):5529–37.CrossRefGoogle Scholar
  127. 127.
    Johnston S, Pippen J Jr, Pivot X, Lichinitser M, Sadeghi S, Dieras V, et al. Lapatinib combined with letrozole versus letrozole and placebo as first-line therapy for postmenopausal hormone receptor-positive metastatic breast cancer. J Clin Oncol (Official Journal of the American Society of Clinical Oncology). 2009;27(33):5538–46.CrossRefGoogle Scholar
  128. 128.
    Burstein HJ, Sun Y, Dirix LY, Jiang Z, Paridaens R, Tan AR, et al. Neratinib, an irreversible ErbB receptor tyrosine kinase inhibitor, in patients with advanced ErbB2-positive breast cancer. J Clin Oncol (Official Journal of the American Society of Clinical Oncology). 2010;28(8):1301–7.CrossRefGoogle Scholar
  129. 129.
    Awada A, Colomer R, Inoue K, Bondarenko I, Badwe RA, Demetriou G, et al. Neratinib plus paclitaxel vs trastuzumab plus paclitaxel in previously untreated metastatic ERBB2-positive breast cancer: the NEfERT-T randomized clinical trial. JAMA oncology. 2016.Google Scholar
  130. 130.
    Kennecke H, Yerushalmi R, Woods R, Cheang MC, Voduc D, Speers CH, et al. Metastatic behavior of breast cancer subtypes. J Clin Oncol (Official Journal of the American Society of Clinical Oncology). 2010;28(20):3271–7.CrossRefGoogle Scholar
  131. 131.
    Isakoff SJ. Triple-negative breast cancer: role of specific chemotherapy agents. Cancer J. 2010;16(1):53–61.PubMedPubMedCentralCrossRefGoogle Scholar
  132. 132.
    Wahba HA, El-Hadaad HA. Current approaches in treatment of triple-negative breast cancer. Cancer Biol Med. 2015;12(2):106–16.PubMedPubMedCentralGoogle Scholar
  133. 133.
    Wysocki PJ KK, Lamperska K, Zaluski J, Mackiewicz A. Primary resistance to docetaxel-based chemotherapy in metastatic breast cancer patients correlates with a high frequency of BRCA 1 mutations. Med Sci Monit. 2008;14:SC7–SC10.Google Scholar
  134. 134.
    Byrski T, Gronwald J, Huzarski T, Grzybowska E, Budryk M, Stawicka M, et al. Pathologic complete response rates in young women with BRCA1-positive breast cancers after neoadjuvant chemotherapy. J Clin Oncol (Official Journal of the American Society of Clinical Oncology). 2010;28(3):375–9.CrossRefGoogle Scholar
  135. 135.
    Byrski T, Foszczynska-Kloda M, Huzarski T, Dent R, Gronwald J, Cybulski C et al. Cisplatin chemotherapy in the treatment of BRCA-1 positive metastatic breast cancer (MBC). J Clin Oncol 2009;27: abstr 1099.Google Scholar
  136. 136.
    Tutt A, Ellis P, Kilburn L, et al. Abstract S3-01: The TNT trial: a randomized phase III trial of carboplatin (C) compared with docetaxel (D) for patients with metastatic or recurrent locally advanced triple negative or BRCA1/2 breast cancer (CRUK/07/012). Cancer Res May 1, 2015 75; S3-01.hirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium; 9–13 Dec 2014; San Antonio, TX.Google Scholar
  137. 137.
    Schneider BP, Miller KD. Angiogenesis of breast cancer. J Clin Oncol (Official Journal of the American Society of Clinical Oncology). 2005;23(8):1782–90.CrossRefGoogle Scholar
  138. 138.
    Miller K, Wang M, Gralow J, Dickler M, Cobleigh M, Perez EA, et al. Paclitaxel plus bevacizumab versus paclitaxel alone for metastatic breast cancer. N Engl J Med. 2007;357(26):2666–76.PubMedCrossRefGoogle Scholar
  139. 139.
    Miles DW, Chan A, Dirix LY, Cortes J, Pivot X, Tomczak P, et al. Phase III study of bevacizumab plus docetaxel compared with placebo plus docetaxel for the first-line treatment of human epidermal growth factor receptor 2-negative metastatic breast cancer. J Clin Oncol (Official Journal of the American Society of Clinical Oncology). 2010;28(20):3239–47.CrossRefGoogle Scholar
  140. 140.
    Robert NJ, Dieras V, Glaspy J, Brufsky AM, Bondarenko I, Lipatov ON, et al. RIBBON-1: randomized, double-blind, placebo-controlled, phase III trial of chemotherapy with or without bevacizumab for first-line treatment of human epidermal growth factor receptor 2-negative, locally recurrent or metastatic breast cancer. J Clin Oncol. 2011;29(10):1252–60.PubMedCrossRefGoogle Scholar
  141. 141.
    Rossari JR, Metzger-Filho O, Paesmans M, Saini KS, Gennari A, de Azambuja E, et al. Bevacizumab and breast cancer: a meta-analysis of first-line phase III studies and a critical reappraisal of available evidence. J Oncol. 2012;2012:417673.PubMedPubMedCentralCrossRefGoogle Scholar
  142. 142.
    O’Shaughnessy J, Miles D, Gray RJ, et al. A meta-analysis of overall survival data from three randomized trials of bevacizumab (BV) and first-line chemotherapy as treatment for patients with metastatic breast cancer (MBC). J Clin Oncol 2010;28:15s: Abstr 1005.Google Scholar
  143. 143.
    Farmer H, McCabe N, Lord CJ, Tutt AN, Johnson DA, Richardson TB, et al. Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy. Nature. 2005;434(7035):917–21.PubMedCrossRefGoogle Scholar
  144. 144.
    O’Shaughnessy J, Osborne C, Pippen JE, Yoffe M, Patt D, Rocha C, et al. Iniparib plus chemotherapy in metastatic triple-negative breast cancer. N Engl J Med. 2011;364(3):205–14.PubMedCrossRefGoogle Scholar
  145. 145.
    J. O’Shaughnessy LSS, M. A. Danso, H. S. Rugo, K. Miller, D. A. Yardley, R. W. Carlson, R. S. Finn, E. Charpentier, M. Freese, S. Gupta, A. Blackwood-Chirchir, E. P. Winer. A randomized phase III study of iniparib (BSI-201) in combination with gemcitabine/carboplatin (G/C) in metastatic triple-negative breast cancer (TNBC). J Clin Oncol. 2011;29(suppl; abstr 1007).Google Scholar
  146. 146.
    Gelmon KA, Hirte H, Robidoux A, et al. Can we define tumors that will respond to PARP inhibitors? A phase II correlative study of olaparib in advanced serous ovarian cancer and triple-negative breast cancer. J Clin Oncol. 2010;28(15 suppl):3002.CrossRefGoogle Scholar
  147. 147.
    Kumar P, Aggarwal R. An overview of triple-negative breast cancer. Arch Gynecol Obstet. 2016;293(2):247–69.PubMedCrossRefGoogle Scholar
  148. 148.
    Fontanella C, Fanotto V, Rihawi K, Aprile G, Puglisi F. Skeletal metastases from breast cancer: pathogenesis of bone tropism and treatment strategy. Clin Exp Metastasis. 2015;32(8):819–33.PubMedCrossRefGoogle Scholar
  149. 149.
    Dunstan CR, Felsenberg D, Seibel MJ. Therapy insight: the risks and benefits of bisphosphonates for the treatment of tumor-induced bone disease. Nat Clin Pract Oncol. 2007;4(1):42–55.PubMedCrossRefGoogle Scholar
  150. 150.
    Coleman RE. Bisphosphonates in breast cancer. Ann Oncol (Official Journal of the European Society for Medical Oncology)/ESMO. 2005;16(5):687–95.CrossRefGoogle Scholar
  151. 151.
    Kohno N, Aogi K, Minami H, Nakamura S, Asaga T, Iino Y, et al. Zoledronic acid significantly reduces skeletal complications compared with placebo in Japanese women with bone metastases from breast cancer: a randomized, placebo-controlled trial. J Clin Oncol (Official Journal of the American Society of Clinical Oncology). 2005;23(15):3314–21.CrossRefGoogle Scholar
  152. 152.
    Rosen LS, Gordon D, Kaminski M, Howell A, Belch A, Mackey J, et al. Zoledronic acid versus pamidronate in the treatment of skeletal metastases in patients with breast cancer or osteolytic lesions of multiple myeloma: a phase III, double-blind, comparative trial. Cancer J. 2001;7(5):377–87.PubMedGoogle Scholar
  153. 153.
    Lipton A, Small E, Saad F, Gleason D, Gordon D, Smith M, et al. The new bisphosphonate, Zometa (zoledronic acid), decreases skeletal complications in both osteolytic and osteoblastic lesions: a comparison to pamidronate. Cancer Inv. 2002;20(Suppl 2):45–54.CrossRefGoogle Scholar
  154. 154.
    Bamias A, Kastritis E, Bamia C, Moulopoulos LA, Melakopoulos I, Bozas G, et al. Osteonecrosis of the jaw in cancer after treatment with bisphosphonates: incidence and risk factors. J Clin Oncol (Official Journal of the American Society of Clinical Oncology). 2005;23(34):8580–7.CrossRefGoogle Scholar
  155. 155.
    Andrew Louis Himelstein RQ, Paul J. Novotny et al. CALGB 70604 (Alliance): a randomized phase III study of standard dosing vs. longer interval dosing of zoledronic acid in metastatic cancer. J Clin Oncol 2015;33(suppl; abstr 9501).Google Scholar
  156. 156.
    Body JJ, Facon T, Coleman RE, Lipton A, Geurs F, Fan M, et al. A study of the biological receptor activator of nuclear factor-kappaB ligand inhibitor, denosumab, in patients with multiple myeloma or bone metastases from breast cancer. Clin Cancer Res (An Official Journal of the American Association for Cancer Research). 2006;12(4):1221–8.CrossRefGoogle Scholar
  157. 157.
    Brown JE, Coleman RE. Denosumab in patients with cancer-a surgical strike against the osteoclast. Nat Rev Clin Oncol. 2012;9(2):110–8.PubMedCrossRefGoogle Scholar
  158. 158.
    Stopeck AT, Lipton A, Body JJ, Steger GG, Tonkin K, de Boer RH, et al. Denosumab compared with zoledronic acid for the treatment of bone metastases in patients with advanced breast cancer: a randomized, double-blind study. J Clin Oncol (Official Journal of the American Society of Clinical Oncology). 2010;28(35):5132–9.CrossRefGoogle Scholar
  159. 159.
    Martin M, Bell R, Bourgeois H, Brufsky A, Diel I, Eniu A, et al. Bone-related complications and quality of life in advanced breast cancer: results from a randomized phase III trial of denosumab versus zoledronic acid. Clin Cancer Res. 2012;18(17):4841–9.PubMedCrossRefGoogle Scholar
  160. 160.
    Chow E, Harris K, Fan G, Tsao M, Sze WM. Palliative radiotherapy trials for bone metastases: a systematic review. J Clin Oncol (Official Journal of the American Society of Clinical Oncology). 2007;25(11):1423–36.CrossRefGoogle Scholar
  161. 161.
    Hoskin PJ, Stratford MR, Folkes LK, Regan J, Yarnold JR. Effect of local radiotherapy for bone pain on urinary markers of osteoclast activity. Lancet. 2000;355(9213):1428–9.PubMedCrossRefGoogle Scholar
  162. 162.
    Beyzadeoglu M, Ozyigit G, Ebruli C. Basic radiation oncology. Heidelberg: Springer;2010.Google Scholar
  163. 163.
    Roos DE, Turner SL, O’Brien PC, Smith JG, Spry NA, Burmeister BH, et al. Randomized trial of 8 Gy in 1 versus 20 Gy in 5 fractions of radiotherapy for neuropathic pain due to bone metastases (Trans-Tasman Radiation Oncology Group, TROG 96.05). Radiother Oncol (Journal of the European Society for Therapeutic Radiology and Oncology). 2005;75(1):54–63.CrossRefGoogle Scholar
  164. 164.
    Yamada Y, Bilsky MH, Lovelock DM, Venkatraman ES, Toner S, Johnson J, et al. High-dose, single-fraction image-guided intensity-modulated radiotherapy for metastatic spinal lesions. Int J Radiat Oncol Biol Phys. 2008;71(2):484–90.PubMedCrossRefGoogle Scholar
  165. 165.
    Ju DG, Yurter A, Gokaslan ZL, Sciubba DM. Diagnosis and surgical management of breast cancer metastatic to the spine. World J Clin Oncol. 2014;5(3):263–71.PubMedPubMedCentralCrossRefGoogle Scholar
  166. 166.
    Shehadi JA, Sciubba DM, Suk I, Suki D, Maldaun MV, McCutcheon IE, et al. Surgical treatment strategies and outcome in patients with breast cancer metastatic to the spine: a review of 87 patients. Eur Spine J. 2007;16(8):1179–92.PubMedPubMedCentralCrossRefGoogle Scholar
  167. 167.
    Tsao MN, Rades D, Wirth A, Lo SS, Danielson BL, Gaspar LE, et al. Radiotherapeutic and surgical management for newly diagnosed brain metastasis(es): an American Society for Radiation Oncology evidence-based guideline. Pract Radiat Oncol. 2012;2(3):210–25.PubMedPubMedCentralCrossRefGoogle Scholar
  168. 168.
    Patchell RA, Tibbs PA, Walsh JW, Dempsey RJ, Maruyama Y, Kryscio RJ, et al. A randomized trial of surgery in the treatment of single metastases to the brain. N Engl J Med. 1990;322(8):494–500.PubMedCrossRefGoogle Scholar
  169. 169.
    National Comprehensive Cancer Network. Central nervous system cancers (version 1.2014). Available from: http://www.nccn.org.
  170. 170.
    Lesser GJ. Chemotherapy of cerebral metastases from solid tumors. Neurosurg Clin N Am. 1996;7(3):527–36.PubMedGoogle Scholar
  171. 171.
    Park YH, Park MJ, Ji SH, Yi SY, Lim DH, Nam DH, et al. Trastuzumab treatment improves brain metastasis outcomes through control and durable prolongation of systemic extracranial disease in HER2-overexpressing breast cancer patients. Br J Cancer. 2009;100(6):894–900.PubMedPubMedCentralCrossRefGoogle Scholar
  172. 172.
    Dijkers EC, Oude Munnink TH, Kosterink JG, Brouwers AH, Jager PL, de Jong JR, et al. Biodistribution of 89Zr-trastuzumab and PET imaging of HER2-positive lesions in patients with metastatic breast cancer. Clin Pharmacol Ther. 2010;87(5):586–92.PubMedCrossRefGoogle Scholar
  173. 173.
    Willett A, Wilkinson JB, Shah C, Mehta MP. Management of solitary and multiple brain metastases from breast cancer. Indian J Med Paediatr Oncol (Official Journal of Indian Society of Medical & Paediatric Oncology). 2015;36(2):87–93.CrossRefGoogle Scholar
  174. 174.
    Li J, Bentzen SM, Renschler M, Mehta MP. Regression after whole-brain radiation therapy for brain metastases correlates with survival and improved neurocognitive function. J Clin Oncol (Official Journal of the American Society of Clinical Oncology). 2007;25(10):1260–6.CrossRefGoogle Scholar
  175. 175.
    Patchell RA, Tibbs PA, Regine WF, Dempsey RJ, Mohiuddin M, Kryscio RJ, et al. Postoperative radiotherapy in the treatment of single metastases to the brain: a randomized trial. JAMA. 1998;280(17):1485–9.PubMedCrossRefGoogle Scholar
  176. 176.
    Andrews DW, Scott CB, Sperduto PW, Flanders AE, Gaspar LE, Schell MC, et al. Whole brain radiation therapy with or without stereotactic radiosurgery boost for patients with one to three brain metastases: phase III results of the RTOG 9508 randomised trial. Lancet. 2004;363(9422):1665–72.PubMedCrossRefGoogle Scholar
  177. 177.
    Tomasello G, Bedard PL, de Azambuja E, Lossignol D, Devriendt D, Piccart-Gebhart MJ. Brain metastases in HER2-positive breast cancer: the evolving role of lapatinib. Crit Rev Oncol/Hematol. 2010;75(2):110–21.CrossRefGoogle Scholar
  178. 178.
    Gondi V, Mehta M, Pugh S, Tome W, Kanner A, Caine C, et al. Memory preservation with conformal avoidance of the hippocampus during whole-brain radiotherapy (WBRT) for patients with brain metastases: primary endpoint results of RTOG 0933. Oral presentation at 2013 Annual Meeting of the American Society for Radiation Oncology (ASTRO), Atlanta, Georgia, 23 Sept 2013.Google Scholar
  179. 179.
    Kondziolka D, Patel A, Lunsford LD, Kassam A, Flickinger JC. Stereotactic radiosurgery plus whole brain radiotherapy versus radiotherapy alone for patients with multiple brain metastases. Int J Radiat Oncol Biol Phys. 1999;45(2):427–34.PubMedCrossRefGoogle Scholar
  180. 180.
    Robbins JR, Ryu S, Kalkanis S, Cogan C, Rock J, Movsas B, et al. Radiosurgery to the surgical cavity as adjuvant therapy for resected brain metastasis. Neurosurgery. 2012;71(5):937–43.PubMedCrossRefGoogle Scholar
  181. 181.
    Chang EL, Wefel JS, Hess KR, Allen PK, Lang FF, Kornguth DG, et al. Neurocognition in patients with brain metastases treated with radiosurgery or radiosurgery plus whole-brain irradiation: a randomised controlled trial. Lancet Oncol. 2009;10(11):1037–44.PubMedCrossRefGoogle Scholar
  182. 182.
    Brown PD, Pugh S, Laack NN, Wefel JS, Khuntia D, Meyers C, et al. Memantine for the prevention of cognitive dysfunction in patients receiving whole-brain radiotherapy: a randomized, double-blind, placebo-controlled trial. Neuro-oncology. 2013;15(10):1429–37.PubMedPubMedCentralCrossRefGoogle Scholar
  183. 183.
    Howlader M, Heaton N, Rela M. Resection of liver metastases from breast cancer: towards a management guideline. Int J Surg. 2011;9(4):285–91.PubMedCrossRefGoogle Scholar
  184. 184.
    Kubota K, Makuuchi M, Kusaka K, Kobayashi T, Miki K, Hasegawa K, et al. Measurement of liver volume and hepatic functional reserve as a guide to decision-making in resectional surgery for hepatic tumors. Hepatology. 1997;26(5):1176–81.PubMedGoogle Scholar
  185. 185.
    Ganz PA, Stanton AL. Living with metastatic breast cancer. Adv Exp Med Biol. 2015;862:243–54.PubMedCrossRefGoogle Scholar
  186. 186.
    Low CA BT, Stanton AL. Adaptation in the face of advanced cancer. In Feuerstein M, editors. Handbook of cancer survivorship. Heidelberg: Springer; 2007. p. 211–228.Google Scholar
  187. 187.
    de Raaf PJ, Sleijfer S, Lamers CH, Jager A, Gratama JW, van der Rijt CC. Inflammation and fatigue dimensions in advanced cancer patients and cancer survivors: an explorative study. Cancer. 2012;118(23):6005–11.PubMedCrossRefGoogle Scholar
  188. 188.
    Okamura H, Watanabe T, Narabayashi M, Katsumata N, Ando M, Adachi I, et al. Psychological distress following first recurrence of disease in patients with breast cancer: prevalence and risk factors. Breast Cancer Res Treat. 2000;61(2):131–7.PubMedCrossRefGoogle Scholar
  189. 189.
    Andersen BL, Shapiro CL, Farrar WB, Crespin T, Wells-Digregorio S. Psychological responses to cancer recurrence. Cancer. 2005;104(7):1540–7.PubMedPubMedCentralCrossRefGoogle Scholar
  190. 190.
    Yang HC, Thornton LM, Shapiro CL, Andersen BL. Surviving recurrence: psychological and quality-of-life recovery. Cancer. 2008;112(5):1178–87.PubMedPubMedCentralCrossRefGoogle Scholar
  191. 191.
    Yang HC, Brothers B, Andersen BL. Stress and quality of life in breast cancer recurrence: moderation or mediation of coping? Ann Behav Med. 2008;35:188–197.Google Scholar
  192. 192.
    Nabholtz JM, Buzdar A, Pollak M, Harwin W, Burton G, Mangalik A, et al. Anastrozole is superior to tamoxifen as first-line therapy for advanced breast cancer in postmenopausal women: results of a North American multicenter randomized trial. Arimidex Study Group. J Clin Oncol. 2000;18(22):3758–67.PubMedCrossRefGoogle Scholar
  193. 193.
    Mouridsen H, Gershanovich M, Sun Y, Perez-Carrion R, Boni C, Monnier A, et al. Superior efficacy of letrozole versus tamoxifen as first-line therapy for postmenopausal women with advanced breast cancer: results of a phase III study of the International Letrozole Breast Cancer Group. J Clin Oncol (Official Journal of the American Society of Clinical Oncology). 2001;19(10):2596–606.CrossRefGoogle Scholar
  194. 194.
    Paridaens RJ, Dirix LY, Beex LV, Nooij M, Cameron DA, Cufer T, et al. Phase III study comparing exemestane with tamoxifen as first-line hormonal treatment of metastatic breast cancer in postmenopausal women: the European Organisation for Research and Treatment of Cancer Breast Cancer Cooperative Group. J Clin Oncol (Official Journal of the American Society of Clinical Oncology). 2008;26(30):4883–90.Google Scholar
  195. 195.
    Riemsma R, Forbes CA, Kessels A, Lykopoulos K, Amonkar MM, Rea DW, et al. Systematic review of aromatase inhibitors in the first-line treatment for hormone sensitive advanced or metastatic breast cancer. Breast Cancer Res Treat. 2010;123(1):9–24.PubMedCrossRefGoogle Scholar
  196. 196.
    Howell A, Robertson JF, Abram P, Lichinitser MR, Elledge R, Bajetta E, et al. Comparison fulvestrant versus tamoxifen for the treatment of advanced breast cancer in postmenopausal women previously untreated with endocrine therapy: a multinational, double-blind, randomized trial. J Clin Oncol (Official Journal of the American Society of Clinical Oncology). 2004;22(9):1605–13.CrossRefGoogle Scholar
  197. 197.
    Di Leo A, Jerusalem G, Petruzelka L, Torres R, Bondarenko IN, Khasanov R, et al. Results of the CONFIRM phase III trial comparing fulvestrant 250 mg with fulvestrant 500 mg in postmenopausal women with estrogen receptor-positive advanced breast cancer. J Clin Oncol (Official Journal of the American Society of Clinical Oncology). 2010;28(30):4594–600.CrossRefGoogle Scholar
  198. 198.
    Martin M, Loibl S, von Minckwitz G, Morales S, Martinez N, Guerrero A, et al. Phase III trial evaluating the addition of bevacizumab to endocrine therapy as first-line treatment for advanced breast cancer: the letrozole/fulvestrant and avastin (LEA) study. J Clin Oncol (Official Journal of the American Society of Clinical Oncology). 2015;33(9):1045–52.CrossRefGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2016

Authors and Affiliations

  • Berta Sousa
    • 1
  • Joana M. Ribeiro
    • 1
  • Domen Ribnikar
    • 2
  • Fátima Cardoso
    • 1
    Email author
  1. 1.Breast UnitChampalimaud Clinical CenterLisbonPortugal
  2. 2.Medical Oncology DepartmentInstitute of Oncology LjubljanaLjubljanaSlovenia

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