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Treatment approach to metastatic hormone receptor-positive, HER2-negative breast cancer: Endocrine therapy

Authors
Michael J Naughton, MD
Cynthia X Ma, MD, PhD
Maura Dickler, MD
Section Editor
Daniel F Hayes, MD
Deputy Editor
Sadhna R Vora, MD

INTRODUCTION

In general, breast cancer can be broken down into three biologic subgroups, each of which has a direct bearing on treatment choices: 1) those that express the estrogen receptor (ER), 2) those that express the human epidermal growth factor receptor 2 (HER2), and 3) those that do not express either of these, nor the progesterone receptor (triple-negative).

Although metastatic breast cancer is unlikely to be cured, there have been meaningful improvements in survival due to the availability of more effective systemic therapies, including endocrine therapy in the treatment of hormone-sensitive disease.

Endocrine therapy for metastatic hormone receptor-positive, HER2-negative breast cancer is presented here. The treatment of HER2-positive disease is discussed elsewhere, as is chemotherapy (in general) for metastatic breast cancer. Other topics including the approach to breast cancer and the role of adjunctive therapy, such as pain medications and bone modifying agents, are also covered separately.

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

(See "Systemic treatment of metastatic breast cancer in women: Chemotherapy" and "Systemic treatment for HER2-positive metastatic breast cancer".)

                         

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Literature review current through: Apr 2017. | This topic last updated: May 17, 2017.
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References
Top
  1. Lindström LS, Karlsson E, Wilking UM, et al. Clinically used breast cancer markers such as estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 are unstable throughout tumor progression. J Clin Oncol 2012; 30:2601.
  2. Wilcken N, Hornbuckle J, Ghersi D. Chemotherapy alone versus endocrine therapy alone for metastatic breast cancer. Cochrane Database Syst Rev 2003; :CD002747.
  3. Sledge GW Jr, Hu P, Falkson G, et al. Comparison of chemotherapy with chemohormonal therapy as first-line therapy for metastatic, hormone-sensitive breast cancer: An Eastern Cooperative Oncology Group study. J Clin Oncol 2000; 18:262.
  4. Robertson JF, Bondarenko IM, Trishkina E, et al. Fulvestrant 500 mg versus anastrozole 1 mg for hormone receptor-positive advanced breast cancer (FALCON): an international, randomised, double-blind, phase 3 trial. Lancet 2016; 388:2997.
  5. Di Leo A, Jerusalem G, Petruzelka L, 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 2010; 28:4594.
  6. Fribbens C, O'Leary B, Kilburn L, et al. Plasma ESR1 Mutations and the Treatment of Estrogen Receptor-Positive Advanced Breast Cancer. J Clin Oncol 2016; 34:2961.
  7. Chandarlapaty S, Chen D, He W, et al. Prevalence of ESR1 Mutations in Cell-Free DNA and Outcomes in Metastatic Breast Cancer: A Secondary Analysis of the BOLERO-2 Clinical Trial. JAMA Oncol 2016; 2:1310.
  8. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines), Breast Cancer (version 1.2014). http://www.nccn.org/professionals/physician_gls/pdf/breast.pdf (Accessed on January 28, 2014).
  9. Klijn JG, Beex LV, Mauriac L, et al. Combined treatment with buserelin and tamoxifen in premenopausal metastatic breast cancer: a randomized study. J Natl Cancer Inst 2000; 92:903.
  10. Carlson RW, Theriault R, Schurman CM, et al. Phase II trial of anastrozole plus goserelin in the treatment of hormone receptor-positive, metastatic carcinoma of the breast in premenopausal women. J Clin Oncol 2010; 28:3917.
  11. Park IH, Ro J, Lee KS, et al. Phase II parallel group study showing comparable efficacy between premenopausal metastatic breast cancer patients treated with letrozole plus goserelin and postmenopausal patients treated with letrozole alone as first-line hormone therapy. J Clin Oncol 2010; 28:2705.
  12. Taylor CW, Green S, Dalton WS, et al. Multicenter randomized clinical trial of goserelin versus surgical ovariectomy in premenopausal patients with receptor-positive metastatic breast cancer: an intergroup study. J Clin Oncol 1998; 16:994.
  13. Sunderland MC, Osborne CK. Tamoxifen in premenopausal patients with metastatic breast cancer: a review. J Clin Oncol 1991; 9:1283.
  14. FDA approves Ibrance for postmenopausal women with advanced breast cancer. http://www.fda.gov/newsevents/newsroom/pressannouncements/ucm432871.htm.
  15. Finn RS, Martin M, Rugo HS, et al. Palbociclib and Letrozole in Advanced Breast Cancer. N Engl J Med 2016; 375:1925.
  16. Hortobagyi GN, Stemmer SM, Burris HA, et al. Ribociclib as First-Line Therapy for HR-Positive, Advanced Breast Cancer. N Engl J Med 2016; 375:1738.
  17. DeFriend DJ, Anderson E, Bell J, et al. Effects of 4-hydroxytamoxifen and a novel pure antioestrogen (ICI 182780) on the clonogenic growth of human breast cancer cells in vitro. Br J Cancer 1994; 70:204.
  18. Dauvois S, White R, Parker MG. The antiestrogen ICI 182780 disrupts estrogen receptor nucleocytoplasmic shuttling. J Cell Sci 1993; 106 ( Pt 4):1377.
  19. DeFriend DJ, Howell A, Nicholson RI, et al. Investigation of a new pure antiestrogen (ICI 182780) in women with primary breast cancer. Cancer Res 1994; 54:408.
  20. Osborne CK, Coronado-Heinsohn EB, Hilsenbeck SG, et al. Comparison of the effects of a pure steroidal antiestrogen with those of tamoxifen in a model of human breast cancer. J Natl Cancer Inst 1995; 87:746.
  21. Howell A, Robertson JF, Abram P, et al. Comparison of 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 2004; 22:1605.
  22. Robertson JF, Llombart-Cussac A, Rolski J, et al. Activity of fulvestrant 500 mg versus anastrozole 1 mg as first-line treatment for advanced breast cancer: results from the FIRST study. J Clin Oncol 2009; 27:4530.
  23. Howell A, Pippen J, Elledge RM, et al. Fulvestrant versus anastrozole for the treatment of advanced breast carcinoma: a prospectively planned combined survival analysis of two multicenter trials. Cancer 2005; 104:236.
  24. Di Leo A, Jerusalem G, Petruzelka L, et al. Final overall survival: fulvestrant 500 mg vs 250 mg in the randomized CONFIRM trial. J Natl Cancer Inst 2014; 106:djt337.
  25. Robertson JF, Osborne CK, Howell A, et al. Fulvestrant versus anastrozole for the treatment of advanced breast carcinoma in postmenopausal women: a prospective combined analysis of two multicenter trials. Cancer 2003; 98:229.
  26. Chia S, Gradishar W, Mauriac L, 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 2008; 26:1664.
  27. Mauriac L, Romieu G, Bines J. Activity of fulvestrant versus exemestane in advanced breast cancer patients with or without visceral metastases: data from the EFECT trial. Breast Cancer Res Treat 2009; 117:69.
  28. Mehta RS, Barlow WE, Albain KS, et al. Combination anastrozole and fulvestrant in metastatic breast cancer. N Engl J Med 2012; 367:435.
  29. Bergh J, Jönsson PE, Lidbrink EK, 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 2012; 30:1919.
  30. Johnston SR, Kilburn LS, Ellis P, 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; 14:989.
  31. 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; 98:1285.
  32. Campos SM, Guastalla JP, Subar M, et al. A comparative study of exemestane versus anastrozole in patients with postmenopausal breast cancer with visceral metastases. Clin Breast Cancer 2009; 9:39.
  33. Geisler J, Haynes B, Anker G, et al. Influence of letrozole and anastrozole on total body aromatization and plasma estrogen levels in postmenopausal breast cancer patients evaluated in a randomized, cross-over study. J Clin Oncol 2002; 20:751.
  34. Sainsbury R. Aromatase inhibition in the treatment of advanced breast cancer: is there a relationship between potency and clinical efficacy? Br J Cancer 2004; 90:1733.
  35. Dixon JM, Renshaw L, Langridge C, et al. Anastrozole and letrozole: an investigation and comparison of quality of life and tolerability. Breast Cancer Res Treat 2011; 125:741.
  36. Rose C, Vtoraya O, Pluzanska A, 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; 39:2318.
  37. Beresford M, Tumur I, Chakrabarti J, et al. A qualitative systematic review of the evidence base for non-cross-resistance between steroidal and non-steroidal aromatase inhibitors in metastatic breast cancer. Clin Oncol (R Coll Radiol) 2011; 23:209.
  38. Baselga J, Campone M, Piccart M, et al. Everolimus in postmenopausal hormone-receptor-positive advanced breast cancer. N Engl J Med 2012; 366:520.
  39. Turner NC, Ro J, André F, et al. Palbociclib in Hormone-Receptor-Positive Advanced Breast Cancer. N Engl J Med 2015; 373:209.
  40. Cristofanilli M, Turner NC, Bondarenko I, et al. Fulvestrant plus palbociclib versus fulvestrant plus placebo for treatment of hormone-receptor-positive, HER2-negative metastatic breast cancer that progressed on previous endocrine therapy (PALOMA-3): final analysis of the multicentre, double-blind, phase 3 randomised controlled trial. Lancet Oncol 2016; 17:425.
  41. Verma S, Bartlett CH, Schnell P, et al. Palbociclib in Combination With Fulvestrant in Women With Hormone Receptor-Positive/HER2-Negative Advanced Metastatic Breast Cancer: Detailed Safety Analysis From a Multicenter, Randomized, Placebo-Controlled, Phase III Study (PALOMA-3). Oncologist 2016; 21:1165.
  42. Harbeck N, Iyer S, Turner N, et al. Quality of life with palbociclib plus fulvestrant in previously treated hormone receptor-positive, HER2-negative metastatic breast cancer: patient-reported outcomes from the PALOMA-3 trial. Ann Oncol 2016; 27:1047.
  43. Cancer Genome Atlas Network. Comprehensive molecular portraits of human breast tumours. Nature 2012; 490:61.
  44. Piccart M, Hortobagyi GN, Campone M, et al. Everolimus plus exemestane for hormone-receptor-positive, human epidermal growth factor receptor-2-negative advanced breast cancer: overall survival results from BOLERO-2†. Ann Oncol 2014; 25:2357.
  45. Bachelot T, Bourgier C, Cropet C, 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; 30:2718.
  46. Kornblum NS S, Manola J, Klein P, et al. PrECOG 0102: A randomized, double-blind, phase II trial of fulvestrant plus everolimus or placebo in post-menopausal. SABCS 2016; S1-02.
  47. Thürlimann B, Robertson JF, Nabholtz JM, et al. Efficacy of tamoxifen following anastrozole ('Arimidex') compared with anastrozole following tamoxifen as first-line treatment for advanced breast cancer in postmenopausal women. Eur J Cancer 2003; 39:2310.
  48. Abrams J, Aisner J, Cirrincione C, et al. Dose-response trial of megestrol acetate in advanced breast cancer: cancer and leukemia group B phase III study 8741. J Clin Oncol 1999; 17:64.
  49. Willemse PH, van der Ploeg E, Sleijfer DT, et al. A randomized comparison of megestrol acetate (MA) and medroxyprogesterone acetate (MPA) in patients with advanced breast cancer. Eur J Cancer 1990; 26:337.
  50. Kornblith AB, Hollis DR, Zuckerman E, et al. Effect of megestrol acetate on quality of life in a dose-response trial in women with advanced breast cancer. The Cancer and Leukemia Group B. J Clin Oncol 1993; 11:2081.
  51. Mattsson W. Current status of high dose progestin treatment in advanced breast cancer. Breast Cancer Res Treat 1983; 3:231.
  52. Ellis MJ, Gao F, Dehdashti F, et al. Lower-dose vs high-dose oral estradiol therapy of hormone receptor-positive, aromatase inhibitor-resistant advanced breast cancer: a phase 2 randomized study. JAMA 2009; 302:774.
  53. Ingle JN, Ahmann DL, Green SJ, et al. Randomized clinical trial of diethylstilbestrol versus tamoxifen in postmenopausal women with advanced breast cancer. N Engl J Med 1981; 304:16.
  54. GOLDENBERG IS. RESULTS OF STUDIES OF THE COOPERATIVE BREAST CANCER GROUP--1961-63. Cancer Chemother Rep 1964; 41:SUPPL:1.
  55. Coombes RC, Dearnaley D, Humphreys J, et al. Danazol treatment of advanced breast cancer. Cancer Treat Rep 1980; 64:1073.
  56. Manni A, Arafah BM, Pearson OH. Androgen-induced remissions after antiestrogen and hypophysectomy in stage IV breast cancer. Cancer 1981; 48:2507.
  57. Schifeling DJ, Jackson DV, Zekan PJ, Muss HB. Fluoxymesterone as third line endocrine therapy for advanced breast cancer. A phase II trial of the Piedmont Oncology Association. Am J Clin Oncol 1992; 15:233.
  58. Toy W, Shen Y, Won H, et al. ESR1 ligand-binding domain mutations in hormone-resistant breast cancer. Nat Genet 2013; 45:1439.
  59. Robinson DR, Wu YM, Vats P, et al. Activating ESR1 mutations in hormone-resistant metastatic breast cancer. Nat Genet 2013; 45:1446.
  60. Li S, Shen D, Shao J, et al. Endocrine-therapy-resistant ESR1 variants revealed by genomic characterization of breast-cancer-derived xenografts. Cell Rep 2013; 4:1116.
  61. Dickler MN, Tolaney SM, Rugo HS, et al. MONARCH1: Results from a phase II study of abemaciclib, a CDK4 and CDK6 inhibitor, as monotherapy, in patients with HR+/HER2- breast cancer, after chemotherapy for advanced disease. J Clin Oncol 2016; ASCO #510.
  62. Cochrane DR, Bernales S, Jacobsen BM, et al. Role of the androgen receptor in breast cancer and preclinical analysis of enzalutamide. Breast Cancer Res 2014; 16:R7.
  63. Dickler MN, Barry WT, Cirrincione CT, et al. Phase III Trial Evaluating Letrozole As First-Line Endocrine Therapy With or Without Bevacizumab for the Treatment of Postmenopausal Women With Hormone Receptor-Positive Advanced-Stage Breast Cancer: CALGB 40503 (Alliance). J Clin Oncol 2016; 34:2602.
  64. Martín M, Loibl S, von Minckwitz G, 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 2015; 33:1045.