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Breast Disease pp 163-172 | Cite as

Prognostic and Predictive Factors

  • Sitki Tuzlali
  • Ekrem Yavuz
Chapter

Abstract

In this chapter, the pathological features that are used in assessing the prognosis of breast cancer patients and predicting the tumor response to therapeutic agents are discussed. These features include classic pathological parameters: tumor size, lymph node status, tumor grade, histopathological types, and lymphovascular invasion. Other pathological parameters are usually determined by immunohistochemical and/or in situ hybridization methods, namely, steroid hormone receptor and HER2 (c-erb B-2) analysis. The role of assessing the proliferative activity of breast carcinomas by Ki-67 and its limitations are discussed. Molecular profiling and gene expression tests in breast carcinoma and their use, advantages and disadvantages are also discussed. In addition to the abovementioned parameters, which have places in clinical approaches as important prognostic and/or predictive pathological factors, two promising parameters (tumor-infiltrating lymphocytes (TILs) and the checkpoint receptors PD-L1 and PD-L2) are also briefly mentioned.

Keywords

Breast cancer Prognosis Predictive Pathology Grading Histological type Lymphovascular invasion Steroid receptors HER2 Ki-67 Gene expression tests Tumor-infiltrating lymphocytes (TILs) PDL-1 

References

  1. 1.
    Schnitt SJ. Classification and prognosis of invasive breast cancer: from morphology to molecular taxonomy: long course article. Mod Pathol. 2010;23:60–4.Google Scholar
  2. 2.
    Edge SB, Byrd DR, Carducci MA, Compton CC, editors. AJCC cancer staging manual. 7th ed. New York: Springer; 2009.Google Scholar
  3. 3.
    Giuliano AE, Connolly JL, Edge SB, Mittendorf EA, Rugo HS, Solin LJ, et al. Breast cancer—major changes in the American joint committee on cancer eighth edition cancer staging manual. CA Cancer J Clin. 2017;67(4):290–303.PubMedGoogle Scholar
  4. 4.
    Elston CW, Gresham GA, Rao GS, Zebro T, Haybittle JL, Kaerney G. The cancer research campaign (Kings/Cambridge) trial for early breast cancer- pathological aspects. Br J Cancer. 1982;45:655–69.PubMedPubMedCentralGoogle Scholar
  5. 5.
    Fisher ER, Sass R, Fisher B, Wickerham L. Pathologic findings from the national surgical adjuvant project for breast cancer (protocol no 4). Discrimination for tenth year treatment failure. Cancer. 1984;53:712–23.PubMedGoogle Scholar
  6. 6.
    Carter GL, Allen C, Henson DE. Relation of tumour size, lymph node status, and survival in 24,740 breast cancer cases. Cancer. 1989;63:181–7.PubMedGoogle Scholar
  7. 7.
    Neville AM, Bettelheim R, Gelber RD, Save-Soderbergh J, Davis BW, Reed R, et al. Predicting treatment responsiveness and prognosis in node-negative breast cancer. J Clin Oncol. 1992;10:696–705.PubMedGoogle Scholar
  8. 8.
    Lakhani S, Ellis IO, Tan PH, van de Vijver MJ, editors. World Health Organization classification of tumors, WHO classification of tumors of the breast. 2nd ed. Lyon: IARC; 2012.Google Scholar
  9. 9.
    Lester SC, Bose S, Chen YY, Connolly JL, de Baca ME, Fitzgibbons PL, et al. Protocol for the examination of specimens from patients with invasive carcinoma of the breast. Protocol applies to all invasive carcinomas of the breast, including microinvasive carcinoma with or without ductal carcinoma in situ (DCIS). Based on AJCC/UICC TNM, 7th edition. Protocol web posting date: January 2016.Google Scholar
  10. 10.
    Veronesi U, Galimberti V, Zurrida S, et al. Prognostic significance of number and level of axillary node metastases in breast cancer. Breast. 1993;2:224–8.Google Scholar
  11. 11.
    Giuliano AE, Hunt KK, Ballman KV, Beitsch PD, Whitworth PW, Blumencranz PW, et al. Axillary dissection vs no axillary dissection in women with invasive breast cancer and sentinel node metastasis: a randomized clinical trial. JAMA. 2011;305(6):569–75.PubMedPubMedCentralGoogle Scholar
  12. 12.
    Elston CW, Ellis IO. Pathological prognostic factors in breast cancer I. The value of histological grade in breast cancer: experience from a large study with long-term follow-up. Histopathology. 1991;19:403–10.PubMedPubMedCentralGoogle Scholar
  13. 13.
    Ellis IO, Al-Sam S, Anderson N, Carder P, Deb R, Girlinget A, et al. Pathology reporting of breast disease in surgical excision specimens incorporating the dataset for histological reporting of breast cancer, June 2016. Published by The Royal College of Pathologists.Google Scholar
  14. 14.
    Rakha EA, El-Sayed ME, Lee AH, Elston CW, Grainge MJ, Hodi Z, et al. Prognostic significance of Nottingham histologic grade in invasive breast carcinoma. J Clin Oncol. 2008;26:3153–8.PubMedGoogle Scholar
  15. 15.
    Rakha EA, Reis-Filho JS, Baehner F, Dabbs DJ. Breast cancer prognostic classification in the molecular era: the role of histological grade. Breast Cancer Res. 2010;12(4):207.PubMedPubMedCentralGoogle Scholar
  16. 16.
    Schwartz AM, Henson DE, Chen D, Rajamarthandan S. Histologic grade remains a prognostic factor for breast cancer regardless of the number of positive lymph nodes and tumor size: a study of 161 708 cases of breast cancer from the SEER Program. Arch Pathol Lab Med. 2014;138(8):1048–52.PubMedGoogle Scholar
  17. 17.
    Pathology reporting of breast disease: a joint document incorporating the third edition of the NHS breast screening programme’s guidelines for pathology reporting in breast cancer screening and the second edition of The Royal College of Pathologists’ minimum dataset for breast cancer histopathology. Sheffield; NHS Cancer Screening Programmes and The Royal College of Pathologists; 2005.Google Scholar
  18. 18.
    Ellis IO, Galea M, Broughton N, Locker A, Blamey RW, Elston CW. Pathological prognostic factors in breast cancer. II, Histological type. Relationship with survival in a large study with long-term follow-up. Histopathology. 1992;20:479–89.PubMedGoogle Scholar
  19. 19.
    Pinder S, Ellis IO, O’Rourke S, Blamey RW, Elston CW. Pathological prognostic factors in breast cancer—vascular invasion: relationship with recurrence and survival in a large series with long-term follow-up. Histopathology. 1994;24(1):41–7.PubMedGoogle Scholar
  20. 20.
    Rakha EA, Martin S, Lee AH, Morgan D, Pharoah PD, Hodi Z, et al. The prognostic significance of lymphovascular invasion in invasive breast carcinoma. Cancer. 2012;118(15):3670–80.PubMedGoogle Scholar
  21. 21.
    Hamy AS, Lam GT, Laas E, Darrigues L, et al. Lymphovascular invasion after neoadjuvant chemotherapy is strongly associated with poor prognosis in breast carcinoma. Breast Cancer Res Treat. 2018;169(2):295–304.PubMedGoogle Scholar
  22. 22.
    Early Breast Cancer Trialists’ Collaborative Group (EBCTCG), Davies C, Godwin J, Gray R, Clarke M, Cutter D, et al. Relevance of breast cancer hormone receptors and other factors to the efficacy of adjuvant tamoxifen: patient-level meta-analysis of randomised trials. Lancet. 2011;378:771–84.Google Scholar
  23. 23.
    Bardou VJ, Arpino G, Elledge RM, Osborne CK, Clark GM. Progesterone receptor status significantly improves outcome prediction over estrogen receptor status alone for adjuvant endocrine therapy in two large breast cancer databases. J Clin Oncol. 2003;21(10):1973–9.PubMedGoogle Scholar
  24. 24.
    Rakha E, Ellis IO. Modern classification of breast cancer: should we stick with morphology or convert to molecular profile characteristics. Adv Anat Pathol. 2011;18(4):255–67.PubMedGoogle Scholar
  25. 25.
    Hammond ME, Hayes DF, Dowsett M, Allred DC, Hagerty KL, Badve S, et al. 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. 2010;28(16):2784–95.PubMedPubMedCentralGoogle Scholar
  26. 26.
    Goldstein NS, Ferkowicz M, Odish E, Mani A, Hastah F. Minimum formalin fixation time for consistent estrogen receptor immunohistochemical staining of invasive breast carcinoma. Am J Clin Pathol. 2003;120:86–92.PubMedGoogle Scholar
  27. 27.
    Yeung C, Hilton J, Clemons M, Mazzarello S. Estrogen, progesterone, and HER2/neu receptor discordance between primary and metastatic breast tumours-a review. Cancer Metastasis Rev. 2016;35(3):427–37.PubMedGoogle Scholar
  28. 28.
    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. 2008;26:1642–9.PubMedGoogle Scholar
  29. 29.
    Perez EA, Suman VJ, Davidson NE, Martino S, Kaufman PA, Lingle WL, et al. HER2 testing by local, central, and reference laboratories in specimens from the North Central Cancer Treatment Group N9831 intergroup adjuvant trial. J Clin Oncol. 2006;24(19):3032–8.PubMedGoogle Scholar
  30. 30.
    Dowsett M, Hanna WM, Kockx M, Penault-Llorca F, Rüschoff J, Gutjahr T, et al. Standardization of HER2 testing: results of an international proficiency-testing ring study. Mod Pathol. 2007;20(5):584–91.PubMedGoogle Scholar
  31. 31.
    Tuzlali S, Yavuz E, Canda T, Güray M, Geçer MO, Süllü Y, et al. In situ hybridization analysis of invasive breast carcinomas with immunohistochemically negative Her-2 status (a national multicenter study). Turk Patoloji Derg. 2014;30(2):87–93.PubMedGoogle Scholar
  32. 32.
    Wolff AC, Hammond ME, Schwartz JN, Hagerty KL, Allred DC, 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;25:1–28.Google Scholar
  33. 33.
    Middleton LP, Price KM, Puig P, Heydon LJ, Tarco E, Sneige N, et al. Implementation of American Society of Clinical Oncology/College of American Pathologists HER2 guideline recommendations in a tertiary care facility increases HER2 immunohistochemistry and fluorescence in situ hybridization concordance and decreases the number of inconclusive cases. Arch Pathol Lab Med. 2009;133:775–80.PubMedGoogle Scholar
  34. 34.
    Liu YH, Xu FP, Rao JY, Zhuang HG, Luo XL, Li L, et al. Justification of the change from 10% to 30% for the immunohistochemical HER2 scoring criterion in breast cancer. Am J Clin Pathol. 2009;132:74–9.PubMedGoogle Scholar
  35. 35.
    Wolff AC, Hammond ME, Hicks DG, Dowsett M, McShane LM, Allison KH, et al. 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. 2013;31:3997–4013.PubMedPubMedCentralGoogle Scholar
  36. 36.
    Wolff AC, Hammond ME, Allison KH, Harvey E, McShane LM, Dowsett M. Human epidermal growth factor receptor 2 testing in breast cancer: American Society of Clinical Oncology/College of American Pathologists clinical practice guideline focused update. Arch Pathol Lab Med. 2018;36(20):2105–22.Google Scholar
  37. 37.
    Kos Z, Dabbs DJ. Biomarker assessment and molecular testing for prognostication in breast cancer. Histopathology. 2016;68:70–85.PubMedGoogle Scholar
  38. 38.
    Goldhirsch A, Winer EP, Coates AS, Gelber RD, Piccart-Gebhart M, Thürlimann B, et al. Personalizing the treatment of women with early breast cancer: highlights of the St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer. Ann Oncol. 2013;24:2206–23.PubMedPubMedCentralGoogle Scholar
  39. 39.
    Cheang MCU, Chia SK, Voduc D, Gao D, Leung S, Snider J, et al. Ki67 index, HER2 status, and prognosis of patients with luminal B breast cancer. J Natl Cancer Inst. 2009;101:736.PubMedPubMedCentralGoogle Scholar
  40. 40.
    Dowsett M, Nielsen TO, A’Hern R, Bartlett J, Coombes RC, Cuzick J, et al. Assessment of Ki67 in breast cancer: recommendations from the international Ki67 in breast cancer working group. J Natl Cancer Inst. 2011;103(22):1656–64.PubMedPubMedCentralGoogle Scholar
  41. 41.
    Zabaglo L, Salter J, Anderson H, Quinn E, Hills M, Detre S, et al. Comparative validation of the SP6 antibody to Ki67 in breast cancer. J Clin. 2010;63(9):800–4.Google Scholar
  42. 42.
    Polley MY, Leung SC, McShane LM, Gao D, Hugh JC, Mastropasqua MG, et al. International Ki67 in breast cancer working group of the breast international group and North American breast cancer group. An international Ki67 reproducibility study. J Natl Cancer Inst. 2013;105(24):1897–906.PubMedPubMedCentralGoogle Scholar
  43. 43.
    Curigliano G, Burstein HJ, Winer EP, Gnant M, Dubsky P, Loibl S, et al. De-escalating and escalating treatments for early-stage breast cancer: the St. Gallen international expert consensus conference on the primary therapy of early breast cancer. Ann Oncol. 2017;28:1700–12.PubMedPubMedCentralGoogle Scholar
  44. 44.
    Perou CM, Sørlie T, Eisen MB, van de Rijn M, Jeffrey SS, Rees CA, et al. Molecular portraits of human breast tumours. Nature. 2000;406:747–52.PubMedGoogle Scholar
  45. 45.
    Ades F, Zardavas D, Bozovic-Spasojevic I, Pugliano L, et al. Luminal B breast cancer: molecular characterization, clinical management, and future perspectives. J Clin Oncol, 2014. 32(25):2794–803.  https://doi.org/10.1200/JCO.2013.54.1870.PubMedGoogle Scholar
  46. 46.
    Weigelt B, Geyer FC, Jorge S, Reis-Filho JS. Histological types of breast cancer: how special are they? Mol Oncol. 2010;4:192–208.PubMedPubMedCentralGoogle Scholar
  47. 47.
    Foulkes WD, Smith IE, Reis-Filho JS. Triple-negative breast cancer. N Engl J Med. 2010;363:1938–48.PubMedGoogle Scholar
  48. 48.
    Dabbs DJ, Klein ME, Mohsin SK, Tubbs RR, Shuai Y, Bhargava R. High false-negative rate of HER2 quantitative reverse transcription polymerase chain reaction of the oncotype DX test: an independent quality assurance study. J Clin Oncol. 2011;29:4279–85.PubMedGoogle Scholar
  49. 49.
    Van’t Veer LJ, Dai H, van de Vijver MJ, He YD, Hart AA, Mao M, et al. Gene expression profiling predicts clinical outcome of breast cancer. Nature. 2002;415:530–6.Google Scholar
  50. 50.
    Bueno-de-Mesquita JM, Linn SC, Keijzer R, Wesseling J, Nuyten DS, van Krimpen C, et al. Validation of 70-gene prognosis signature in node-negative breast cancer. Breast Cancer Res Treat. 2009;117:483–95.PubMedGoogle Scholar
  51. 51.
    Mook S, Schmidt MK, Weigelt B, Kreike B, Eekhout I, van de Vijver MJ, et al. The 70-gene prognosis signature predicts early metastasis in breast cancer patients between 55 and 70 years of age. Ann Oncol. 2010;21:717–22.PubMedGoogle Scholar
  52. 52.
    Mook S, Schmidt MK, Viale G, Pruneri G, Eekhout I, Floore A, et al. 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. 2009;116:295–302.PubMedGoogle Scholar
  53. 53.
    Drukker CA, Bueno-de-Mesquita JM, Knauer M, van Tinteren H, et al. A prospective evaluation of a breast cancer prognosis signature in the observational RASTER study. Int J Cancer. 2013;133:929–36.PubMedPubMedCentralGoogle Scholar
  54. 54.
    Rutgers E, Piccart-Gebhart MJ, Bogaerts J, Delaloge S, Veer LV, Rubio IT, et al. The EORTC 10041/BIG 03-04 MINDACT trial is feasible: results of the pilot phase. Eur J Cancer. 2011;00:2742–9.Google Scholar
  55. 55.
    Viale G, de Snoo FA, Slaets L, Bogaerts J, van ‘t Veer L, Rutgers EJ, et al. MINDACT investigators immunohistochemical versus molecular (BluePrint and MammaPrint) subtyping of breast carcinoma. Outcome results from the EORTC 10041/BIG 3-04 MINDACT trial. Breast Cancer Res Treat. 2017;  https://doi.org/10.1007/s10549-017-4509-9.PubMedGoogle Scholar
  56. 56.
    Paik S, Shak S, Tang G, Kim C, Baker J, Cronin M, et al. A multigene assay to predict recurrence of tamoxifen-treated, node-negative breast cancer. N Engl J Med. 2004;351(27):2817–26.PubMedGoogle Scholar
  57. 57.
    Sparano JA, Gray RJ, Makowe DF, Pritchard KI, Albain KS, Hayes DF, et al. Prospective validation of a 21-Gene expression assay in breast cancer. N Engl J Med. 2015;373:2005–14.PubMedPubMedCentralGoogle Scholar
  58. 58.
    Parker JS, Mullins M, Cheang MC, Leung S, Voduc D, Vickery T, et al. Supervised risk predictor of breast cancer based on intrinsic subtypes. J Clin Oncol. 2009;27:1160–7.PubMedPubMedCentralGoogle Scholar
  59. 59.
    Nielsen TO, Parker JS, Leung S, Voduc D, Ebbert M, Vickery T, et al. A comparison of PAM50 intrinsic subtyping with immunohistochemistry and clinical prognostic factors in tamoxifen-treated estrogen receptor-positive breast cancer. Clin Cancer Res. 2010;16:5222–32.PubMedPubMedCentralGoogle Scholar
  60. 60.
    Nielsen T, Wallden B, Schaper C, Ferree S, Liu S, Gao D, et al. 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. 2014;14:177.PubMedPubMedCentralGoogle Scholar
  61. 61.
    Dowsett M, Sestak I, Lopez-Knowles E, Sidhu K, Dunbier AK, Cowens JW, et al. Comparison of PAM50 risk of recurrence score with Oncotype DX and IHC4 for predicting risk of distant recurrence after endocrine therapy. J Clin Oncol. 2013;31:2783–90.PubMedGoogle Scholar
  62. 62.
    Gnant M, Filipits M, Greil R, Stöger H, Jakesz R, Bago-Horvath Z, et al. 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. 2014;25:339–45.PubMedGoogle Scholar
  63. 63.
    Bartlett JM, Bayani J, Marshall A, Dunn JA et al. Comparing breast cancer multiparameter tests in the OPTIMA prelim trial: no test is more equal than the others. J Natl Cancer Inst. 2016;108(9):  https://doi.org/10.1093/jnci/djw050.PubMedPubMedCentralGoogle Scholar
  64. 64.
    Wein L, Savas P, Luen SJ, Virassamy B, Salgado R, Loi S. Clinical validity and utility of tumor-ınfiltrating lymphocytes in routine clinical practice for breast cancer patients: current and future directions. Front Oncol. 2017;7:156.  https://doi.org/10.3389/fonc.2017.00156. eCollection 2017.PubMedPubMedCentralGoogle Scholar
  65. 65.
    Denkert C, von Minckwitz G, Darb-Esfahani S, Lederer B, et al. Tumour-infiltrating lymphocytes and prognosis in different subtypes of breast cancer: a pooled analysis of 3771 patients treated with neoadjuvant therapy. Lancet Oncol. 2018;19(1):40–50.  https://doi.org/10.1016/S1470-2045(17)30904-X.PubMedGoogle Scholar
  66. 66.
    Salgado R, Denkert C, Demaria S, Sirtaine N. The evaluation of tumor-infiltrating lymphocytes (TILs) in breast cancer: recommendations by an International TILs Working Group 2014. Ann Oncol. 2015;26(2):259–71.  https://doi.org/10.1093/annonc/mdu450.PubMedGoogle Scholar
  67. 67.
    Budhathoki N, Dhakal A, Opyrchal M. Immune checkpoint inhibitors in triple negative breast cancer. Theranostics Can Res. 2017;1:1–4.Google Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Sitki Tuzlali
    • 1
    • 2
  • Ekrem Yavuz
    • 2
  1. 1.Tuzlali Private Pathology LaboratoryIstanbulTurkey
  2. 2.Department of Pathology, Istanbul Medical FacultyIstanbul UniversityIstanbulTurkey

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