Skip to main content
SpringerLink
Log in
SpringerLink
Log in

Prognostic and Predictive Biomarkers of Endocrine Responsiveness for Estrogen Receptor Positive Breast Cancer

  • Chapter
  • First Online:
Novel Biomarkers in the Continuum of Breast Cancer

Part of the book series: Advances in Experimental Medicine and Biology ((BCRF,volume 882))

Abstract

The estrogen-dependent nature of breast cancer is the fundamental basis for endocrine therapy. The presence of estrogen receptor (ER), the therapeutic target of endocrine therapy, is a prerequisite for this therapeutic approach. However, estrogen-independent growth often exists de novo at diagnosis or develops during the course of endocrine therapy. Therefore ER alone is insufficient in predicting endocrine therapy efficacy. Several RNA-based multigene assays are now available in clinical practice to assess distant recurrence risk, with majority of these assays evaluated in patients treated with 5 years of adjuvant endocrine therapy. While MammaPrint and Oncotype Dx are most predictive of recurrence risk within the first 5 years of diagnosis, Prosigna, Breast Cancer Index (BCI), and EndoPredict Clin have also demonstrated utility in predicting late recurrence. In addition, PAM50, or Prosigna, provides further biological insights by classifying breast cancers into intrinsic molecular subtypes. Additional strategies are under investigation in prospective clinical trials to differentiate endocrine sensitive and resistant tumors and include on-treatment Ki-67 and Preoperative Endocrine Prognostic Index (PEPI) score in the setting of neoadjuvant endocrine therapy. These biomarkers have become important tools in clinical practice for the identification of low risk patients for whom chemotherapy could be avoided. However, there is much work ahead toward the development of a molecular classification that informs the biology and novel therapeutic targets in high-risk disease as chemotherapy has only modest benefit in this population. The recognition of somatic mutations and their relationship to endocrine therapy responsiveness opens important opportunities toward this goal.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Early Breast Cancer Trialists’ Collaborative G (2011) Relevance of breast cancer hormone receptors and other factors to the efficacy of adjuvant tamoxifen: patient-level meta-analysis of randomised trials. Lancet 378:771–784

    Article  CAS  Google Scholar 

  2. Josefsson ML, Leinster SJ (2010) Aromatase inhibitors versus tamoxifen as adjuvant hormonal therapy for oestrogen sensitive early breast cancer in post-menopausal women: meta-analyses of monotherapy, sequenced therapy and extended therapy. Breast 19:76–83

    Article  PubMed  Google Scholar 

  3. Ellis MJ, Suman V, McCall L et al (2012) Z1031B Neoadjuvant aromatase inhibitor trial: a phase 2 study of triage to chemotherapy based on 2 to 4 week Ki67 level > 10 %. San Antonio Breast Cancer Symposium. San Antonio, Texas, 2012, pp Abstract PD07-01

    Google Scholar 

  4. Early Breast Cancer Trialists’ Collaborative G, Peto R, Davies C et al (2012) Comparisons between different polychemotherapy regimens for early breast cancer: meta-analyses of long-term outcome among 100,000 women in 123 randomised trials. Lancet 379:432–444

    Article  CAS  PubMed  Google Scholar 

  5. Davies C, Pan H, Godwin J et al (2013) Long-term effects of continuing adjuvant tamoxifen to 10 years versus stopping at 5 years after diagnosis of oestrogen receptor-positive breast cancer: ATLAS, a randomised trial. Lancet 381:805–816

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Gray RG, Rea D, Handley K et al (2013) aTTom: long-term effects of continuing adjuvant tamoxifen to 10 years versus stopping at 5 years in 6953 women with early breast cancer., ASCO Annual Meeting. Chicago, IL, 2013, pp Abstract 05

    Google Scholar 

  7. Goss PE, Ingle JN, Martino S et al (2003) A randomized trial of letrozole in postmenopausal women after five years of tamoxifen therapy for early-stage breast cancer. N Engl J Med 349:1793–1802

    Article  CAS  PubMed  Google Scholar 

  8. Perou CM, Sorlie T, Eisen MB et al (2000) Molecular portraits of human breast tumours. Nature 406:747–752

    Article  CAS  PubMed  Google Scholar 

  9. Sorlie T, Perou C, Tibshirani R et al (2001) Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci U S A 98:10869–10874

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Dowsett M, Smith IE, Ebbs SR et al (2005) Short-term changes in Ki-67 during neoadjuvant treatment of primary breast cancer with anastrozole or tamoxifen alone or combined correlate with recurrence-free survival. Clin Cancer Res 11:951s–958s

    CAS  PubMed  Google Scholar 

  11. Dowsett M, Smith IE, Ebbs SR et al (2007) Prognostic value of Ki67 expression after short-term presurgical endocrine therapy for primary breast cancer. J Natl Cancer Inst 99:167–170

    Article  CAS  PubMed  Google Scholar 

  12. Ellis MJ, Tao Y, Luo J et al (2008) Outcome prediction for estrogen receptor-positive breast cancer based on postneoadjuvant endocrine therapy tumor characteristics. J Natl Cancer Inst 100:1380–1388

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Ellis MJ, Ding L, Shen D et al (2012) Whole-genome analysis informs breast cancer response to aromatase inhibition. Nature 486:353–360

    CAS  PubMed  PubMed Central  Google Scholar 

  14. Toy W, Shen Y, Won H et al (2013) ESR1 ligand-binding domain mutations in hormone-resistant breast cancer. Nat Genet 45:1439–1445

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Robinson DR, Wu YM, Vats P et al (2013) Activating ESR1 mutations in hormone-resistant metastatic breast cancer. Nat Genet 45:1446–1451

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Li S, Shen D, Shao J et al (2013) Endocrine-therapy-resistant ESR1 variants revealed by genomic characterization of breast-cancer-derived xenografts. Cell Rep 4:1116–1130

    Article  CAS  PubMed  Google Scholar 

  17. Zhang QX, Borg A, Wolf DM et al (1997) An estrogen receptor mutant with strong hormone-independent activity from a metastatic breast cancer. Cancer Res 57:1244–1249

    CAS  PubMed  Google Scholar 

  18. Merenbakh-Lamin K, Ben-Baruch N, Yeheskel A et al (2013) D538G mutation in estrogen receptor-α: a novel mechanism for acquired endocrine resistance in breast cancer. Cancer Res 73:6856–6864

    Article  CAS  PubMed  Google Scholar 

  19. Harvey JM, Clark GM, Osborne CK et al (1999) Estrogen receptor status by immunohistochemistry is superior to the ligand-binding assay for predicting response to adjuvant endocrine therapy in breast cancer. J Clin Oncol 17:1474

    CAS  PubMed  Google Scholar 

  20. Khoshnoud MR, Lofdahl B, Fohlin H et al (2011) Immunohistochemistry compared to cytosol assays for determination of estrogen receptor and prediction of the long-term effect of adjuvant tamoxifen. Breast Cancer Res Treat 126:421–430

    Article  CAS  PubMed  Google Scholar 

  21. Molino A, Micciolo R, Turazza M et al (1997) Prognostic significance of estrogen receptors in 405 primary breast cancers: a comparison of immunohistochemical and biochemical methods. Breast Cancer Res Treat 45:241–249

    Article  CAS  PubMed  Google Scholar 

  22. Ellis MJ, Coop A, Singh B et al (2001) Letrozole is more effective neoadjuvant endocrine therapy than tamoxifen for ErbB-1- and/or ErbB-2-positive, estrogen receptor-positive primary breast cancer: evidence from a phase III randomized trial. J Clin Oncol 19:3808–3816

    CAS  PubMed  Google Scholar 

  23. Allred DC, Harvey JM, Berardo M et al (1998) Prognostic and predictive factors in breast cancer by immunohistochemical analysis. Mod Pathol 11:155–168

    CAS  PubMed  Google Scholar 

  24. Smith IE, Dowsett M, Ebbs SR et al (2005) Neoadjuvant treatment of postmenopausal breast cancer with anastrozole, tamoxifen, or both in combination: the Immediate preoperative anastrozole, tamoxifen, or combined with tamoxifen (IMPACT) multicenter double-blind randomized trial. J Clin Oncol 23:5108–5116

    Article  CAS  PubMed  Google Scholar 

  25. McGuire WL, De La Garza M, Chamness GC (1977) Evaluation of estrogen receptor assays in human breast cancer tissue. Cancer Res 37:637–639

    CAS  PubMed  Google Scholar 

  26. Alberts SR, Ingle JN, Roche PR et al (1996) Comparison of estrogen receptor determinations by a biochemical ligand-binding assay and immunohistochemical staining with monoclonal antibody ER1D5 in females with lymph node positive breast carcinoma entered on two prospective clinical trials. Cancer 78:764–772

    Article  CAS  PubMed  Google Scholar 

  27. Elledge RM, Green S, Pugh R et al (2000) Estrogen receptor (ER) and progesterone receptor (PgR), by ligand-binding assay compared with ER, PgR and pS2, by immuno-histochemistry in predicting response to tamoxifen in metastatic breast cancer: a Southwest Oncology Group Study. Int J Cancer 89:111–117

    Article  CAS  PubMed  Google Scholar 

  28. Barnes DM, Harris WH, Smith P et al (1996) Immunohistochemical determination of oestrogen receptor: comparison of different methods of assessment of staining and correlation with clinical outcome of breast cancer patients. Br J Cancer 74:1445–1451

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Allred DC (2008) Problems and solutions in the evaluation of hormone receptors in breast cancer. J Clin Oncol 26:2433–2435

    Article  PubMed  Google Scholar 

  30. Hammond MEH, Hayes DF, Dowsett M et al (2010) American Society of Clinical Oncology/College of American Pathologists guideline recommendations for immunohistochemical testing of estrogen and progesterone receptors in breast cancer. J Clin Oncol 28:2784–2795

    Article  PubMed  PubMed Central  Google Scholar 

  31. Hammond ME, Hayes DF, Dowsett M et al (2010) American Society of Clinical Oncology/College of American Pathologists guideline recommendations for immunohistochemical testing of estrogen and progesterone receptors in breast cancer (unabridged version). Arch Pathol Lab Med 134:e48–e72

    CAS  PubMed  Google Scholar 

  32. Dowsett M, Allred C, Knox J et al (2008) Relationship between quantitative estrogen and progesterone receptor expression and human epidermal growth factor receptor 2 (HER-2) status with recurrence in the Arimidex, Tamoxifen, Alone or in Combination trial. J Clin Oncol 26:1059–1065

    Article  CAS  PubMed  Google Scholar 

  33. Mauriac L, Keshaviah A, Debled M et al (2007) Predictors of early relapse in postmenopausal women with hormone receptor-positive breast cancer in the BIG 1-98 trial. Ann Oncol 18:859–867

    Article  CAS  PubMed  Google Scholar 

  34. Viale G, Regan MM, Maiorano E et al (2007) Prognostic and predictive value of centrally reviewed expression of estrogen and progesterone receptors in a randomized trial comparing letrozole and tamoxifen adjuvant therapy for postmenopausal early breast cancer: BIG 1-98. J Clin Oncol 25:3846–3852

    Article  PubMed  Google Scholar 

  35. Lal P, Tan LK, Chen B (2005) Correlation of HER-2 status with estrogen and progesterone receptors and histologic features in 3655 invasive breast carcinomas. Am J Clin Pathol 123:541–546

    Article  CAS  PubMed  Google Scholar 

  36. Slamon DJ, Clark GM, Wong SG et al (1987) Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science 235:177–182

    Article  CAS  PubMed  Google Scholar 

  37. Pietras RJ, Arboleda J, Reese DM et al (1995) HER-2 tyrosine kinase pathway targets estrogen receptor and promotes hormone-independent growth in human breast cancer cells. Oncogene 10:2435–2446

    CAS  PubMed  Google Scholar 

  38. Oh AS, Lorant LA, Holloway JN et al (2001) Hyperactivation of MAPK induces loss of ERalpha expression in breast cancer cells. Mol Endocrinol 15:1344–59

    CAS  PubMed  Google Scholar 

  39. Dowsett M, Houghton J, Iden C et al (2006) Benefit from adjuvant tamoxifen therapy in primary breast cancer patients according oestrogen receptor, progesterone receptor, EGF receptor and HER2 status. Ann Oncol 17:818–826

    Article  CAS  PubMed  Google Scholar 

  40. De Placido S, De Laurentiis M, Carlomagno C et al (2003) Twenty-year results of the Naples GUN randomized trial: predictive factors of adjuvant tamoxifen efficacy in early breast cancer. Clin Cancer Res 9:1039–1046

    PubMed  Google Scholar 

  41. Ellis MJ, Tao Y, Young O et al (2006) Estrogen-independent proliferation is present in estrogen-receptor HER2-positive primary breast cancer after neoadjuvant letrozole. J Clin Oncol 24:3019–3025

    Article  CAS  PubMed  Google Scholar 

  42. Rasmussen BB, Regan MM, Lykkesfeldt AE et al (2008) Adjuvant letrozole versus tamoxifen according to centrally-assessed ERBB2 status for postmenopausal women with endocrine-responsive early breast cancer: supplementary results from the BIG 1-98 randomised trial. Lancet Oncol 9:23–28

    Article  CAS  PubMed  Google Scholar 

  43. Piccart-Gebhart MJ, Procter M, Leyland-Jones B et al (2005) Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer. N Engl J Med 353:1659–1672

    Article  CAS  PubMed  Google Scholar 

  44. Gerdes J, Schwab U, Lemke H et al (1983) Production of a mouse monoclonal antibody reactive with a human nuclear antigen associated with cell proliferation. Int J Cancer 31:13–20

    Article  CAS  PubMed  Google Scholar 

  45. Pinder SE, Wencyk P, Sibbering DM et al (1995) Assessment of the new proliferation marker MIB1 in breast carcinoma using image analysis: associations with other prognostic factors and survival. Br J Cancer 71:146–149

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Ellis MJ, Luo J, Tao Y et al (2009) Tumor Ki67 proliferation index within 4 weeks of initiating neoadjuvant endocrine therapy for early identification of non-responders, San Antonio Breast Cancer Symposium. San Antonio, Texas, pp abstract 78

    Google Scholar 

  47. Goncalves R, Ma C, Luo J et al (2012) Use of neoadjuvant data to design adjuvant endocrine therapy trials for breast cancer. Nat Rev Clin Oncol 9:223–229

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Baum M, Budzar AU, Cuzick J et al (2002) 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 359:2131–2139

    Article  CAS  PubMed  Google Scholar 

  49. Ellis MJ, Coop A, Singh B et al (2003) Letrozole inhibits tumor proliferation more effectively than tamoxifen independent of HER1/2 expression status. Cancer Res 63:6523–6531

    CAS  PubMed  Google Scholar 

  50. Ellis MJ, Suman VJ, Hoog J et al (2011) Randomized phase II neoadjuvant comparison between letrozole, anastrozole, and exemestane for postmenopausal women with estrogen receptor-rich stage 2 to 3 breast cancer: clinical and biomarker outcomes and predictive value of the baseline PAM50-based intrinsic subtype—ACOSOG Z1031. J Clin Oncol: Off J Am Soc Clin Oncol 29:2342–2349

    Article  CAS  Google Scholar 

  51. Thurlimann B, Keshaviah A, Coates AS et al (2005) A comparison of letrozole and tamoxifen in postmenopausal women with early breast cancer. N Engl J Med 353:2747–2757

    Article  PubMed  Google Scholar 

  52. Goss PE, Ingle JN, Pritchard KI et al (2013) Exemestane versus anastrozole in postmenopausal women with early breast cancer: NCIC CTG MA.27—a randomized controlled phase III trial. J Clin Oncol 31:1398–1404

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Ellis MJ, Suman VJ, Hoog J et al (2011) Randomized phase II neoadjuvant comparison between letrozole, anastrozole, and exemestane for postmenopausal women with estrogen receptor-rich stage 2–3 breast cancer: clinical and biomarker outcomes and predictive value of the baseline PAM50-based intrinsic subtype—ACOSOG Z1031. J Clin Oncol 29:2342–2349

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Dowsett M, Nielsen TO, A’Hern R et al (2011) Assessment of Ki67 in breast cancer: recommendations from the International Ki67 in breast cancer working group. J Nat Cancer Inst 103:1656–1664

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Sanati S, Suman VJ, Goncalves R et al (2014) Validation of the preoperative endocrine prognostic index in the ACOSOG (Alliance) Z1031 neoadjuvant aromatase inhibitor trial, San Antonio Breast Cancer Symposium, 2014, pp Abstract P4-11–13

    Google Scholar 

  56. Goncalves R, Ma C, Tao Y et al (2013) The development of a standardized Ki-67 assay for the ALTERNATE trial: an experience in academic investigational device development, San Antonio Breast Cancer Symposium, 2013, pp Abstract P3-05–10

    Google Scholar 

  57. Cuzick J, Dowsett M, Pineda S et al (2011) Prognostic value of a combined estrogen receptor, progesterone receptor, Ki-67, and human epidermal growth factor receptor 2 immunohistochemical score and comparison with the genomic health recurrence score in early breast cancer. J Clin Oncol 29:4273–4278

    Article  PubMed  Google Scholar 

  58. Wolff AC, Hammond MEH, Hicks DG et al (2013) Recommendations for human epidermal growth factor receptor 2 testing in breast cancer: American Society of Clinical Oncology/College of American Pathologists clinical practice guideline update. J Clin Oncol 31:3997–4013

    Article  PubMed  Google Scholar 

  59. Sorlie T, Tibshirani R, Parker J et al (2003) Repeated observation of breast tumor subtypes in independent gene expression data sets. Proc Natl Acad Sci U S A 100:8418–8423

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Network TCGA (2012) Comprehensive molecular portraits of human breast tumours. Nature 490:61–70

    Article  CAS  Google Scholar 

  61. van de Vijver MJ, He YD, van’t Veer LJ et al (2002) A gene-expression signature as a predictor of survival in breast cancer. N Engl J Med 347:1999–2009

    Article  PubMed  Google Scholar 

  62. van ’t Veer LJ, Dai H, van de Vijver MJ et al (2002) Gene expression profiling predicts clinical outcome of breast cancer. Nature 415:530–536

    Article  PubMed  Google Scholar 

  63. Buyse M, Loi S, van’t Veer L et al (2006) Validation and clinical utility of a 70-gene prognostic signature for women with node-negative breast cancer. J Natl Cancer Inst 98:1183–1192

    Article  CAS  PubMed  Google Scholar 

  64. Mook S, Schmidt MK, Viale G et al (2009) The 70-gene prognosis-signature predicts disease outcome in breast cancer patients with 1-3 positive lymph nodes in an independent validation study. Breast Cancer Res Treat 116:295–302

    Article  CAS  PubMed  Google Scholar 

  65. Ravdin PM, Siminoff LA, Davis GJ et al (2001) Computer program to assist in making decisions about adjuvant therapy for women with early breast cancer. J Clin Oncol 19:980–991

    CAS  PubMed  Google Scholar 

  66. Bogaerts J, Cardoso F, Buyse M et al (2006) Gene signature evaluation as a prognostic tool: challenges in the design of the MINDACT trial. Nat Clin Pract Oncol 3:540–551

    Article  CAS  PubMed  Google Scholar 

  67. Sapino A, Roepman P, Linn SC et al (2014) MammaPrint molecular diagnostics on formalin-fixed, paraffin-embedded tissue. J Mol Diagn 16:190–197

    Article  CAS  PubMed  Google Scholar 

  68. Paik S, Shak S, Tang G et al (2004) A multigene assay to predict recurrence of tamoxifen-treated, node-negative breast cancer. N Engl J Med 351:2817–2826

    Article  CAS  PubMed  Google Scholar 

  69. Albain KS, Barlow WE, Shak S et al (2010) Prognostic and predictive value of the 21-gene recurrence score assay in postmenopausal women with node-positive, oestrogen-receptor-positive breast cancer on chemotherapy: a retrospective analysis of a randomised trial. Lancet Oncol 11:55–65

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Dowsett M, Cuzick J, Wale C et al (2010) Prediction of risk of distant recurrence using the 21-gene recurrence score in node-negative and node-positive postmenopausal patients with breast cancer treated with anastrozole or tamoxifen: a transATAC study. J Clin Oncol 28:1829–1834

    Article  PubMed  Google Scholar 

  71. Paik S, Tang G, Shak S et al (2006) Gene expression and benefit of chemotherapy in women with node-negative, estrogen receptor-positive breast cancer. J Clin Oncol 24:3726–3734

    Article  CAS  PubMed  Google Scholar 

  72. Sparano JA, Paik S (2008) Development of the 21-gene assay and its application in clinical practice and clinical trials. J Clin Oncol 26:721–728

    Article  PubMed  Google Scholar 

  73. Filipits M, Rudas M, Jakesz R et al (2011) A new molecular predictor of distant recurrence in ER-positive, HER2-negative breast cancer adds independent information to conventional clinical risk factors. Clin Cancer Res 17:6012–6020

    Article  CAS  PubMed  Google Scholar 

  74. Dubsky P, Brase JC, Jakesz R et al (2013) The EndoPredict score provides prognostic information on late distant metastases in ER-POSITIVE/HER2- breast cancer patients. Br J Cancer 109:2959–2964

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Parker JS, Mullins M, Cheang MC et al (2009) Supervised risk predictor of breast cancer based on intrinsic subtypes. J Clin Oncol 27:1160–1167

    Article  PubMed  PubMed Central  Google Scholar 

  76. Ivshina AV, George J, Senko O et al (2006) Genetic reclassification of histologic grade delineates new clinical subtypes of breast cancer. Cancer Res 66:10292–10301

    Article  CAS  PubMed  Google Scholar 

  77. Loi S, Haibe-Kains B, Desmedt C et al (2007) Definition of clinically distinct molecular subtypes in estrogen receptor-positive breast carcinomas through genomic grade. J Clin Oncol 25:1239–1246

    Article  CAS  PubMed  Google Scholar 

  78. Wang Y, Klijn JG, Zhang Y et al (2005) Gene-expression profiles to predict distant metastasis of lymph-node-negative primary breast cancer. Lancet 365:671–679

    Article  CAS  PubMed  Google Scholar 

  79. University of North Carolina Microarray Database. GEO data sets for breast cancer research published papers (Clinical Data updated on 11-6-2007 for Data I, 4-7-2008 for Data II). https://genome.unc.edu/pubsup/breastGEO/

  80. Hess K, Anderson K, Symmans W et al (2006) Pharmacogenomic predictor of sensitivity to preoperative chemotherapy with paclitaxel and fluorouracil, doxorubicin, and cyclophosphamide in breast cancer. J Clin Oncol: Off J Am Soc Clin Oncol 24:4236–4244

    Article  CAS  Google Scholar 

  81. Nielsen TO, Parker JS, Leung S et al (2010) A comparison of PAM50 intrinsic subtyping with immunohistochemistry and clinical prognostic factors in tamoxifen-treated estrogen receptor-positive breast cancer. Clin Cancer Res 16:5222–5232

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Chia SK, Bramwell VH, Tu D et al (2012) A 50-gene intrinsic subtype classifier for prognosis and prediction of benefit from adjuvant tamoxifen. Clin Cancer Res 18:4465–4472

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Nielsen T, Wallden B, Schaper C et al (2014) Analytical validation of the PAM50-based prosigna breast cancer prognostic gene signature assay and nCounter analysis system using formalin-fixed paraffin-embedded breast tumor specimens. BMC Cancer 14:177

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  84. Geiss GK, Bumgarner RE, Birditt B et al (2008) Direct multiplexed measurement of gene expression with color-coded probe pairs. Nat Biotechnol 26:317–325

    Article  CAS  PubMed  Google Scholar 

  85. Reis PP, Waldron L, Goswami RS et al (2011) mRNA transcript quantification in archival samples using multiplexed, color-coded probes. BMC Biotechnol 11:46

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Dowsett M, Sestak I, Lopez-Knowles E et al (2013) Comparison of PAM50 risk of recurrence score with oncotype DX and IHC4 for predicting risk of distant recurrence after endocrine therapy. J Clin Oncol 31:2783–2790

    Article  PubMed  Google Scholar 

  87. Gnant M, Filipits M, Greil R et al (2014) Predicting distant recurrence in receptor-positive breast cancer patients with limited clinicopathological risk: using the PAM50 risk of recurrence score in 1478 postmenopausal patients of the ABCSG-8 trial treated with adjuvant endocrine therapy alone. Ann Oncol 25:339–345

    Article  CAS  PubMed  Google Scholar 

  88. Simon RM, Paik S, Hayes DF (2009) Use of archived specimens in evaluation of prognostic and predictive biomarkers. J Nat Cancer Inst 101:1446–1452

    Article  PubMed  PubMed Central  Google Scholar 

  89. Filipits M, Nielsen TO, Rudas M et al (2014) The PAM50 risk-of-recurrence score predicts risk for late distant recurrence after endocrine therapy in postmenopausal women with endocrine-responsive early breast cancer. Clin Cancer Res 20:1298–1305

    Article  CAS  PubMed  Google Scholar 

  90. Sestak I, Cuzick J, Dowsett M et al (2014) Prediction of late distant recurrence after 5 years of endocrine treatment: a combined analysis of patients from the Austrian breast and colorectal cancer study group 8 and arimidex, tamoxifen alone or in combination randomized trials using the PAM50 risk of recurrence score. J Clin Oncol 33(916):922

    Google Scholar 

  91. Jerevall PL, Ma XJ, Li H et al (2011) Prognostic utility of HOXB13[thinsp]:[thinsp]IL17BR and molecular grade index in early-stage breast cancer patients from the Stockholm trial. Br J Cancer 104:1762–1769

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Jankowitz R, Cooper K, Erlander M et al (2011) Prognostic utility of the breast cancer index and comparison to adjuvant! Online in a clinical case series of early breast cancer. Breast Cancer Res 13:R98

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Zhang Y, Schnabel CA, Schroeder BE et al (2013) Breast cancer index identifies early-stage estrogen receptor-positive breast cancer patients at risk for early- and late-distant recurrence. Clin Cancer Res 19:4196–4205

    Article  CAS  PubMed  Google Scholar 

  94. Sgroi DC, Sestak I, Cuzick J et al (2013) Prediction of late distant recurrence in patients with oestrogen-receptor-positive breast cancer: a prospective comparison of the breast-cancer index (BCI) assay, 21-gene recurrence score, and IHC4 in the TransATAC study population. Lancet Oncol 14:1067–1076

    Article  PubMed  PubMed Central  Google Scholar 

  95. Ma CX, Crowder RJ, Ellis MJ (2011) Importance of PI3-kinase pathway in response/resistance to aromatase inhibitors. Steroids 76:750–752

    Article  CAS  PubMed  Google Scholar 

  96. Kalinsky K, Jacks LM, Heguy A et al (2009) PIK3CA mutation associates with improved outcome in breast cancer. Clin Cancer Res 15:5049–5059

    Article  CAS  PubMed  Google Scholar 

  97. Maruyama N, Miyoshi Y, Taguchi T et al (2007) Clinicopathologic analysis of breast cancers with PIK3CA mutations in Japanese women. Clin Cancer Res 13:408–414

    Article  CAS  PubMed  Google Scholar 

  98. Perez-Tenorio G, Alkhori L, Olsson B et al (2007) PIK3CA mutations and PTEN loss correlate with similar prognostic factors and are not mutually exclusive in breast cancer. Clin Cancer Res 13:3577–3584

    Article  CAS  PubMed  Google Scholar 

  99. Sanchez CG, Ma CX, Crowder RJ et al (2011) Preclinical modeling of combined phosphatidylinositol-3-kinase inhibition with endocrine therapy for estrogen receptor-positive breast cancer. Breast Cancer Res 13:R21

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Ellis MJ, Lin L, Crowder R et al (2010) Phosphatidyl-inositol-3-kinase alpha catalytic subunit mutation and response to neoadjuvant endocrine therapy for estrogen receptor positive breast cancer. Breast Cancer Res Treat 119:379–390

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Goldstein TC, Paull EO, Ellis MJ et al (2013) Molecular pathways: extracting medical knowledge from high-throughput genomic data. Clin Cancer Res 19:3114–3120

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Fuqua SAW, Fitzgerald SD, Chamness GC et al (1991) Variant human breast tumor estrogen receptor with constitutive transcriptional activity. Cancer Res 51:105–109

    CAS  PubMed  Google Scholar 

  103. Roodi N, Bailey LR, Kao WY et al (1995) Estrogen receptor gene analysis in estrogen receptor-positive and receptor-negative primary breast cancer. J Natl Cancer Inst 87:446–451

    Article  CAS  PubMed  Google Scholar 

  104. Ma Y, Ambannavar R, Stephans J et al (2014) Fusion transcript discovery in formalin-fixed paraffin-embedded human breast cancer tissues reveals a link to tumor progression. PLoS One 9:e94202

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  105. Veeraraghavan J, Tan Y, Cao XX et al (2014) Recurrent ESR1-CCDC170 rearrangements in an aggressive subset of oestrogen receptor-positive breast cancers. Nat Commun 5:4577

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Ellis MJ, Gao F, Dehdashti F et al (2009) Lower-dose vs high-dose oral estradiol therapy of hormone receptor-positive, aromatase inhibitor-resistant advanced breast cancer: a phase 2 randomized study. JAMA 302:774–780

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Fan P, Agboke FA, McDaniel RE et al (2014) Inhibition of c-Src blocks oestrogen-induced apoptosis and restores oestrogen-stimulated growth in long-term oestrogen-deprived breast cancer cells. Eur J Cancer 50:457–468

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. Paul D, Vukelja SJ, Holmes FA et al (2013) Letrozole plus dasatinib improves progression-free survival (PFS) in hormone receptor-positive, HER2-negative postmenopausal metastatic breast cancer (MBC) patients receiving first-line aromatase inhibitor (AI) therapy. Cancer Res 73:S3–07

    Google Scholar 

  109. Adelaide J, Finetti P, Charafe-Jauffret E et al (2008) Absence of ESR1 amplification in a series of breast cancers. Int J Cancer 123:2970–2972

    Article  CAS  PubMed  Google Scholar 

  110. Holst F, Stahl PR, Ruiz C et al (2007) Estrogen receptor alpha (ESR1) gene amplification is frequent in breast cancer. Nat Genet 39:655–660

    Article  CAS  PubMed  Google Scholar 

  111. Vincent-Salomon A, Raynal V, Lucchesi C et al (2008) ESR1 gene amplification in breast cancer: a common phenomenon? Nat Genet 40:809; author reply 810–812

    Article  CAS  PubMed  Google Scholar 

  112. Reis-Filho JS, Drury S, Lambros MB et al (2008) ESR1 gene amplification in breast cancer: a common phenomenon? Nat Genet 40:809–810; author reply 810–812

    Article  CAS  PubMed  Google Scholar 

  113. Horlings HM, Bergamaschi A, Nordgard SH et al (2008) ESR1 gene amplification in breast cancer: a common phenomenon? Nat Genet 40:807–808; author reply 810–812

    Article  CAS  PubMed  Google Scholar 

  114. Brown LA, Hoog J, Chin SF et al (2008) ESR1 gene amplification in breast cancer: a common phenomenon? Nat Genet 40:806–807; author reply 810–812

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  115. Ooi A, Inokuchi M, Harada S et al (2012) Gene amplification of ESR1 in breast cancers–fact or fiction? A fluorescence in situ hybridization and multiplex ligation-dependent probe amplification study. J Pathol 227:8–16

    Article  CAS  PubMed  Google Scholar 

  116. Albertson DG (2012) ESR1 amplification in breast cancer: controversy resolved? J Pathol 227:1–3

    Article  CAS  PubMed  Google Scholar 

  117. Holst F, Moelans CB, Filipits M et al (2012) On the evidence for ESR1 amplification in breast cancer. Nat Rev Cancer 12:149

    Article  CAS  PubMed  Google Scholar 

  118. Tomita S, Zhang Z, Nakano M et al (2009) Estrogen receptor α gene ESR1 amplification may predict endocrine therapy responsiveness in breast cancer patients. Cancer Sci 100:1012–1017

    Article  CAS  PubMed  Google Scholar 

  119. Moelans CB, Monsuur HN, de Pinth JH et al (2010) ESR1 amplification is rare in breast cancer and is associated with high grade and high proliferation: a multiplex ligation-dependent probe amplification study. Anal Cell Pathol (Amst) 33:13–18

    Article  CAS  Google Scholar 

  120. Moelans CB, Holst F, Hellwinkel O et al (2013) ESR1 amplification in breast cancer by optimized RNase FISH: frequent but low-level and heterogeneous. PLoS One 8:e84189

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  121. Butt AJ, McNeil CM, Musgrove EA et al (2005) 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 12:S47–S59

    Article  CAS  PubMed  Google Scholar 

  122. Fu X, Creighton C, Biswal N et al (2014) Overcoming endocrine resistance due to reduced PTEN levels in estrogen receptor-positive breast cancer by co-targeting mammalian target of rapamycin, protein kinase B, or mitogen-activated protein kinase kinase. Breast Cancer Res 6:430

    Article  CAS  Google Scholar 

  123. McNeil CM, Sergio CM, Anderson LR et al (2006) c-Myc overexpression and endocrine resistance in breast cancer. J Steroid Biochem Mol Biol 102:147–155

    Article  CAS  PubMed  Google Scholar 

  124. Ma XJ, Salunga R, Dahiya S et al (2008) A five-gene molecular grade index and HOXB13:IL17BR are complementary prognostic factors in early stage breast cancer. Clin Cancer Res 14:2601–2608

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Oncology, Department of Medicine, Siteman Cancer Center, Washington University School of Medicine, 660 South Euclid Avenue, 63110, St Louis, MO, USA

    Assoc. Prof. Cynthia X. Ma M.D., Ph.D. & Assoc. Prof. Ron Bose M.D., Ph.D.

  2. Lester and Sue Smith Breast Center, Baylor College of Medicine, One Baylor Plaza, 320A Cullen, MS 600, 77030, Houston, TX, USA

    Prof. Matthew J. Ellis M.B., B.Chir., Ph.D.

Authors
  1. Assoc. Prof. Cynthia X. Ma M.D., Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Assoc. Prof. Ron Bose M.D., Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Prof. Matthew J. Ellis M.B., B.Chir., Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Matthew J. Ellis M.B., B.Chir., Ph.D. .

Editor information

Editors and Affiliations

  1. Johns Hopkins University, Sidney Kimmel Comprehensive Cancer Ctr., BALTIMORE, Maryland, USA

    Vered Stearns

Rights and permissions

Reprints and permissions

Copyright information

© 2016 Breast Cancer Research Foundation

About this chapter

Cite this chapter

Ma, C., Bose, R., Ellis, M. (2016). Prognostic and Predictive Biomarkers of Endocrine Responsiveness for Estrogen Receptor Positive Breast Cancer. In: Stearns, V. (eds) Novel Biomarkers in the Continuum of Breast Cancer. Advances in Experimental Medicine and Biology(), vol 882. Springer, Cham. https://doi.org/10.1007/978-3-319-22909-6_5

Download citation

Publish with us

Policies and ethics

Search

Navigation