Hopes and pitfalls of the molecular classification of breast cancer
Authors:
Aleš Ryška
; Eva Hovorková; Folakemi Sobande; Tomáš Rozkoš; Jan Laco; Helena Hornychová
Authors place of work:
Fingerlandův ústav patologie LF UK a FN, Hradec Králové
Published in the journal:
Čes.-slov. Patol., 51, 2015, No. 1, p. 26-32
Category:
Reviews Article
Summary
Traditional histopathological diagnosis of breast cancer has been extended in recent years through the results of additional methods. Today, the results of the detection of hormone receptors, HER-2/neu, and Ki67 antigen are thus an integral part of the histopathological diagnosis. A critical factor for the success of these tests is the fulfillment of pre-analytical phase conditions - i.e. optimal fixation, as well as taking into account the heterogeneous nature of the neoplastic population.
In addition to the above-mentioned markers - which have become a routine practice in recent years, there are many efforts to include the molecular characteristics of tumors both in tumor classification as well as in the prediction of results of cancer treatment. Most of the work is based on the use of gene expression profiles. On the basis of the detection of increased or decreased expression of a large number of genes, it is possible to find a set of multiple genes correlating with the biological behavior of the tumor. Using this approach, four basic subgroups of breast cancer have been identified - luminal, basal-like, HER-2 enriched and normal gland-like. Over the course of time, the number of molecular categories has expanded - originally a homogenous group of luminal cancers has been subclassified into the luminal A, B and C. Also within basal-like carcinomas additional subgroups have been identified. However, the results of studies dealing with the analysis of gene expression profiles suggest that our understanding of the biology of breast cancer is far from being complete. The individual categories are defined differently in various publications and thus the comparison of the results of these studies is very difficult. Another approach for the molecular classification of breast cancer is the immunohistochemical detection of various proteins used as a surrogate marker instead of the detection of the mRNA of individual genes. The advantage of this approach is the possibility to use even archive material, as well as much lower costs. On the other hand, its main limitation is the inability of parallel detection of thousands of markers, unlike in genomic profiling.
The results of molecular classification are, however, not fundamentally surprising. The fact that breast cancer tumor stem cells can differentiate towards myoepithelial (or basal) and luminal cells has been known for a long time. These two lines of differentiation are - among others - characterized by differential expression of cytoskeletal proteins as well as of other molecules. These findings have been confirmed by the results of molecular studies - either those based on gene expression profiling or immunohistochemical ones. Research results in gene expression profiling have relatively quickly translated into clinical practice. At present, several commercially available certified tests serve as a complementary source of information for decisions about clinical treatment.
Keywords:
breast cancer – luminal – basal-like – triple negative – predictive and prognostic markers – molecular classification – gene expression profiles
Zdroje
1. Vuong D, Simpson PT, Green B, Cummings MC, Lakhani SR. Molecular classification of breast cancer. Virchows Arch 2014; 465(1): 1-14.
2. Bussolati G, Leonardo E. Technical pitfalls potentially affecting diagnoses in immunohistochemistry. J Clin Pathol 2008; 61(11): 1184-1192.
3. Anderson WF, Chatterjee N, Ershler WB, Brawley OW. Estrogen receptor breast cancer phenotypes in the Surveillance, Epidemiology, and End Results database. Breast Cancer Res Treat 2002; 76(1): 27-36.
4. Chu KC, Anderson WF. Rates for breast cancer characteristics by estrogen and progesterone receptor status in the major racial/ethnic groups. Breast Cancer Res Treat 2002; 74(3): 199-211.
5. Cserni G, Francz M, Kalman E, et al. Estrogen receptor negative and progesterone receptor positive breast carcinomas-how frequent are they? Pathol Oncol Res 2011; 17(3): 663-668.
6. Marchio C, Dowsett M, Reis-Filho JS. Revisiting the technical validation of tumour biomarker assays: how to open a Pandora’s box. BMC Med 2011; 9: 41.
7. Barros FF, Powe DG, Ellis IO, Green AR. Understanding the HER family in breast cancer: interaction with ligands, dimerization and treatments. Histopathology 2010; 56(5): 560-572.
8. 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): 177-182.
9. Wolff AC, Hammond ME, Hicks DG, 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(31): 3997-4013.
10. Turashvili G, Bouchalova K, Bouchal J, Kolar Z. Expression of E-cadherin and c-erbB-2/HER-2/neu oncoprotein in high-grade breast cancer. Cesk Patol 2007; 43(3): 87-92.
11. Clark GM, McGuire WL. Follow-up study of HER-2/neu amplification in primary breast cancer. Cancer Res 1991; 51(3): 944-948.
12. Jacobs TW, Gown AM, Yaziji H, Barnes MJ, Schnitt SJ. Comparison of fluorescence in situ hybridization and immunohistochemistry for the evaluation of HER-2/neu in breast cancer. J Clin Oncol 1999; 17(7): 1974-1982.
13. Jacobs TW, Gown AM, Yaziji H, Barnes MJ, Schnitt SJ. HER-2/neu protein expression in breast cancer evaluated by immunohistochemistry. A study of interlaboratory agreement. Am J Clin Pathol 2000; 113(2): 251-258.
14. Pauletti G, Dandekar S, Rong H, et al. Assessment of methods for tissue-based detection of the HER-2/neu alteration in human breast cancer: a direct comparison of fluorescence in situ hybridization and immunohistochemistry. J Clin Oncol 2000; 18(21): 3651-3664.
15. Wolff AC, Hammond ME, Schwartz JN, 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): 118-145.
16. Koninki K, Tanner M, Auvinen A, Isola J. HER-2 positive breast cancer: decreasing proportion but stable incidence in Finnish population from 1982 to 2005. Breast Cancer Res 2009; 11(3): R37.
17. Sobande F, Ryska A. Breast cancer in young women - lessons from an institutional review. Breast J 2014; 20(2): 216-218.
18. Tamimi RM, Baer HJ, Marotti J, et al. Comparison of molecular phenotypes of ductal carcinoma in situ and invasive breast cancer. Breast Cancer Res 2008; 10(4): R67.
19. 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 2010; 28(1): 92-98.
20. Khoury T, Kanehira K, Wang D, et al. Breast carcinoma with amplified HER2: a gene expression signature specific for trastuzumab resistance and poor prognosis. Mod Pathol 2010; 23(10): 1364-1378.
21. Stead LA, Lash TL, Sobieraj JE, et al. Triple-negative breast cancers are increased in black women regardless of age or body mass index. Breast Cancer Res 2009; 11(2): R18.
22. McCormack VA, Joffe M, van den Berg E, et al. Breast cancer receptor status and stage at diagnosis in over 1,200 consecutive public hospital patients in Soweto, South Africa: a case series. Breast Cancer Res 2013; 15(5): R84.
23. Al-Kuraya K, Schraml P, Sheikh S, et al. Predominance of high-grade pathway in breast cancer development of Middle East women. Mod Pathol 2005; 18(7): 891-897.
24. Villarreal-Garza C, Aguila C, Magallanes-Hoyos MC, et al. Breast cancer in young women in Latin America: an unmet, growing burden. Oncologist 2013; 18(12): 1298-1306.
25. Giraldo-Jimenez MY, Cabanillas F, Negron V, et al. Triple negative breast cancer: a retrospective study of Hispanics residing in Puerto Rico. P R Health Sci J 2012; 31(2): 45-51.
26. Pacheco JM, Gao F, Bumb C, Ellis MJ, Ma CX. Racial differences in outcomes of triple-negative breast cancer. Breast Cancer Res Treat 2013; 138(1): 281-289.
27. Viale G, Giobbie-Hurder A, Regan MM, et al. Prognostic and predictive value of centrally reviewed Ki-67 labeling index in postmenopausal women with endocrine-responsive breast cancer: results from Breast International Group Trial 1-98 comparing adjuvant tamoxifen with letrozole. J Clin Oncol 2008; 26(34): 5569-5575.
28. Dowsett M, Nielsen TO, A’Hern R, 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): 1656-1664.
29. Varga Z, Diebold J, Dommann-Scherrer C, et al. How reliable is Ki-67 immunohistochemistry in grade 2 breast carcinomas? A QA study of the Swiss Working Group of Breast- and Gynecopathologists. PLoS One 2012; 7(5): e37379.
30. Goldhirsch A, Winer EP, Coates AS, 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. 2013 Ann Oncol 2013; 24(9): 2206-2223.
31. Reis-Filho JS, Simpson PT, Gale T, Lakhani SR. The molecular genetics of breast cancer: the contribution of comparative genomic hybridization. Pathol Res Pract 2005; 201(11): 713-725.
32. Buerger H, Otterbach F, Simon R, et al. Comparative genomic hybridization of ductal carcinoma in situ of the breast-evidence of multiple genetic pathways. J Pathol 1999; 187(4): 396-402.
33. Buerger H, Otterbach F, Simon R, et al. Different genetic pathways in the evolution of invasive breast cancer are associated with distinct morphological subtypes. J Pathol 1999; 189(4): 521-526.
34. Perou CM, Sorlie T, Eisen MB, et al. Molecular portraits of human breast tumours. Nature 2000; 406(6797): 747-752.
35. van ‘t Veer LJ, Dai H, van de Vijver MJ, et al. Gene expression profiling predicts clinical outcome of breast cancer. Nature 2002; 415(6871): 530-536.
36. van de Vijver MJ, He YD, van’t Veer LJ, et al. A gene-expression signature as a predictor of survival in breast cancer. N Engl J Med 2002; 347(25): 1999-2009.
37. Sorlie T, Perou CM, Tibshirani R, et al. Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci U S A 2001; 98(19): 10869-10874.
38. Sotiriou C, Neo SY, McShane LM, et al. Breast cancer classification and prognosis based on gene expression profiles from a population-based study. Proc Natl Acad Sci U S A 2003; 100(18): 10393-10398.
39. Badve S, Dabbs DJ, Schnitt SJ, et al. Basal-like and triple-negative breast cancers: a critical review with an emphasis on the implications for pathologists and oncologists. Mod Pathol 2011; 24(2): 157-167.
40. Green AR, Powe DG, Rakha EA, et al. Identification of key clinical phenotypes of breast cancer using a reduced panel of protein biomarkers. Br J Cancer 2013; 109(7): 1886-1894.
41. Boecker W, Buerger H. Evidence of progenitor cells of glandular and myoepithelial cell lineages in the human adult female breast epithelium: a new progenitor (adult stem) cell concept. Cell Prolif 2003; 36 (Suppl 1): 73-84.
42. Boecker W, Buerger H, Schmitz K, et al. Ductal epithelial proliferations of the breast: a biological continuum? Comparative genomic hybridization and high-molecular-weight cytokeratin expression patterns. J Pathol 2001; 195(4): 415-421.
43. Otterbach F, Bankfalvi A, Bergner S, Decker T, Krech R, Boecker W. Cytokeratin 5/6 immunohistochemistry assists the differential diagnosis of atypical proliferations of the breast Histopathology. 2000; 37(3): 232-240.
44. Sorlie T. Molecular portraits of breast cancer: tumour subtypes as distinct disease entities. Eur J Cancer 2004; 40(18): 2667-2675.
45. Sotiriou C, Wirapati P, Loi S, et al. Gene expression profiling in breast cancer: understanding the molecular basis of histologic grade to improve prognosis. J Natl Cancer Inst 2006; 98(4): 262-272.
46. Al Tamimi DM, Shawarby MA, Ahmed A, Hassan AK, AlOdaini AA. Protein expression profile and prevalence pattern of the molecular classes of breast cancer--a Saudi population based study. BMC Cancer 2010; 10: 223.
47. Habashy HO, Powe DG, Abdel-Fatah TM, et al. A review of the biological and clinical characteristics of luminal-like oestrogen receptor-positive breast cancer. Histopathology 2012; 60(6): 854-863.
48. Cheang MC, Chia SK, Voduc D, et al. Ki67 index, HER2 status, and prognosis of patients with luminal B breast cancer. J Natl Cancer Inst 2009; 101(10): 736-750.
49. Prat A, Perou CM. Deconstructing the molecular portraits of breast cancer. Mol Oncol 2011; 5(1): 5-23.
50. Loi S, Sotiriou C, Haibe-Kains B, et al. Gene expression profiling identifies activated growth factor signaling in poor prognosis (Luminal-B) estrogen receptor positive breast cancer. BMC Med Genomics 2009; 2: 37.
51. Bhargava R, Striebel J, Beriwal S, et al. Prevalence, morphologic features and proliferation indices of breast carcinoma molecular classes using immunohistochemical surrogate markers. Int J Clin Exp Pathol 2009; 2(5): 444-455.
52. Bhargava R, Beriwal S, Dabbs DJ, et al. Immunohistochemical surrogate markers of breast cancer molecular classes predicts response to neoadjuvant chemotherapy: a single institutional experience with 359 cases. Cancer 2010; 116(6): 1431-1439.
53. Jacquemier J, Ginestier C, Rougemont J, et al. Protein expression profiling identifies subclasses of breast cancer and predicts prognosis. Cancer Res 2005; 65(3): 767-779.
54. Gazinska P, Grigoriadis A, Brown JP, et al. Comparison of basal-like triple-negative breast cancer defined by morphology, immunohistochemistry and transcriptional profiles. Mod Pathol 2013; 26(7): 955-966.
55. Korsching E, Jeffrey SS, Meinerz W, Decker T, Boecker W, Buerger H. Basal carcinoma of the breast revisited: an old entity with new interpretations. J Clin Pathol 2008; 61(5): 553-560.
56. Grim J, Jandik P, Slanska I, et al. Low expression of NQO1 predicts pathological complete response to neoadjuvant chemotherapy in breast cancer patients treated with TAC regimen. Folia Biol (Praha) 2012; 58(5): 185-192.
57. Linn SC, Van ‘t Veer LJ. Clinical relevance of the triple-negative breast cancer concept: genetic basis and clinical utility of the concept. Eur J Cancer 2009; 45 Suppl 1: 11-26.
58. Galanina N, Bossuyt V, Harris LN. Molecular predictors of response to therapy for breast cancer. Cancer J 2011; 17(2): 96-103.
59. Dowsett M, Cuzick J, Wale C, et al. 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 2010; 28(11): 1829-1834.
60. Mook S, Van’t Veer LJ, Rutgers EJ, Piccart-Gebhart MJ, Cardoso F. Individualization of therapy using Mammaprint: from development to the MINDACT Trial. Cancer Genomics Proteomics 2007; 4(3): 147-155.
61. Bueno-de-Mesquita JM, Linn SC, Keijzer R, et al. Validation of 70-gene prognosis signature in node-negative breast cancer. Breast Cancer Res Treat 2009; 117(3): 483-495.
62. Sapino A, Roepman P, Linn SC, et al. MammaPrint molecular diagnostics on formalin-fixed, paraffin-embedded tissue. J Mol Diagn 2014; 16(2): 190-197.
63. Cusumano PG, Generali D, Ciruelos E, et al. European inter-institutional impact study of MammaPrint. Breast 2014; 23(4): 423-428.
64. Exner R, Bago-Horvath Z, Bartsch R, et al. The multigene signature MammaPrint impacts on multidisciplinary team decisions in ER, HER2 early breast cancer. Br J Cancer 2014;111(5): 837-842.
65. Mamounas EP, Tang G, Fisher B, et al. Association between the 21-gene recurrence score assay and risk of locoregional recurrence in node-negative, estrogen receptor-positive breast cancer: results from NSABP B-14 and NSABP B-20. J Clin Oncol 2010; 28(10): 1677-1683.
66. Lee JJ, Shen J. Is the Oncotype DX assay necessary in strongly estrogen receptor-positive breast cancers? Am Surg 2011; 77(10): 1364-1367.
67. Paik S. Is gene array testing to be considered routine now? Breast 2011; 20 (Suppl 3): S87-91.
68. Brenton JD, Carey LA, Ahmed AA, Caldas C. Molecular classification and molecular forecasting of breast cancer: ready for clinical application? J Clin Oncol 2005; 23(29): 7350-7360.
69. Cornejo KM, Kandil D, Khan A, Cosar EF. Theranostic and molecular classification of breast cancer. Arch Pathol Lab Med 2014; 138(1): 44-56.
70. Dowsett M, Sestak I, Lopez-Knowles E, 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(22): 2783-2790.
71. Cuzick J, Dowsett M, Pineda S, et al. 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 2011; 29(32): 4273-4278.
72. Kondo M, Hoshi SL, Ishiguro H, Toi M. Economic evaluation of the 70-gene prognosis-signature (MammaPrint(R)) in hormone receptor-positive, lymph node-negative, human epidermal growth factor receptor type 2-negative early stage breast cancer in Japan. Breast Cancer Res Treat 2012; 133(2): 759-768.
73. Yang M, Rajan S, Issa AM. Cost effectiveness of gene expression profiling for early stage breast cancer: a decision-analytic model. Cancer 2012; 118(20): 5163-5170.
74. Kamal AH, Loprinzi CL, Reynolds C, et al. Breast medical oncologists’ use of standard prognostic factors to predict a 21-gene recurrence score. Oncologist 2011; 16(10): 1359-1366.
75. Buerger H, Mommers EC, Littmann R, et al. Ductal invasive G2 and G3 carcinomas of the breast are the end stages of at least two different lines of genetic evolution. J Pathol 2001; 194(2): 165-170.
76. Hornychova H, Melichar B, Tomsova M, Mergancova J, Urminska H, Ryska A. Tumor-infiltrating lymphocytes predict response to neoadjuvant chemotherapy in patients with breast carcinoma. Cancer Invest 2008; 26(10): 1024-1031.
Štítky
Anatomical pathology Forensic medical examiner ToxicologyČlánok vyšiel v časopise
Czecho-Slovak Pathology
2015 Číslo 1
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