Features of tumor heterogeneity in regional metastasis of breast cancer

Cover Page

Cite item

Full Text

Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription Access


The review looked at the issues of tumor heterogeneity in breast cancer. Tumor heterogeneity is classified according to the main feature demonstrating regional differences within a tumor (for example, heterogeneity of clinical manifestations, histological heterogeneity, heterogeneity of protein expression, etc.) and by tumor regions (differences between primary tumors and metastases, differences between cell clones within a single tumor node, etc.). Temporal heterogeneity is also distinguished, which manifests itself in the clonal evolution of tumor cells. The review covers the heterogeneity in the expression of four biomarkers from the “gold standard” for immunohistochemical staining of breast cancer: estrogen receptors, progesterone receptors, Her2/neu and Ki67 in primary tumor tissue and regional metastases. According to various studies, discordance in estrogen receptor status of primary tumor cells and metastases was observed with a frequency of 4 to 62%, progesterone receptors — from 12 to 54%, Her2/neu — from 0 to 24%, Ki67 — from 4 to 39%. The results of studies of changes in the expression levels of individual markers in breast cancer metastases, as well as the heterogeneity of surrogate subtypes of tumor tissue in metastasis, are briefly described. Possible reasons for heterogeneity in the expression of key prognostic and predictive markers by primary tumor and metastatic cells, such as artificial factors at the preanalytic and analytic stages of the study, polyclonality of the primary tumor before metastasis, clonal evolution of tumor cells during metastasis, selection of tumor clones under the therapy are highlighted.

Full Text

Restricted Access

About the authors

K K Konyshev

Ural State Medical University; Institute of medical cellular technologies

Email: prof-ssazonov@yandex.ru
Russian Federation, Yekaterinburg, Russia; Yekaterinburg, Russia

S V Sazonov

Ural State Medical University; Institute of medical cellular technologies

Author for correspondence.
Email: prof-ssazonov@yandex.ru
Russian Federation, Yekaterinburg, Russia; Yekaterinburg, Russia


  1. Aurilio G., Disalvatore D., Pruneri G., Bagnardi V., Viale G., Curigliano G., Adamoli L., Munzone E., Sciandivasci A., De Vita F., Goldhirsch A., Nole F. A meta-analysis of oestrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 discordance between primary breast cancer and metastases. Eur. J. Cancer. 2014; 50 (2): 277–289. doi: 10.1016/j.ejca.2013.10.004.
  2. Konyshev K.V., Sazonov S.V. Changes in expression of immunohistochemical markers in regional breast cancer etastases. Arkhiv patologii. 2020; 82 (4): 19–26. (In Russ.) doi: 10.17116/patol20208204119.
  3. Erofeeva L.M., Mni­khovich M.V. Related characteristic of lymphoid infiltration in invasive cancer of breast of the different molecu­lar-biological subtypes. Byulleten' eksperimental'noy biologii i meditsiny. 2021; 171 (1): 80–85. (In Russ.) doi: 10.47056/0365-9615-2021-171-1-80-85.
  4. Mnikhovich M.V., Midiber K.Yu., Gallyamova A.R., Erzieva A.G., Luchinin V.V., Anistratov S.V., Shilov A.V. Immunohistochemical evaluation of cadherin-catenin complex expression in breast cancer. Zhurnal anatomii i gistopatologii. 2017; 6 (1): 63–68. (In Russ.) doi: 10.18499/2225-7357-2017-6-1-63-68.
  5. Alekseenko I.V., Kuzmich A.I., Pleshkan V.V., Tyulkina D.V., Zinovyeva M.V., Kostina M.B., Sverdlov E.D. The cause of cancer mutations: improvable bad life or inevitable stochastic replication errors? Molecular biology. 2016; 50 (6): 799–811. (In Russ.) doi: 10.1134/S0026893316060030.
  6. Zardavas D., Irrthum A., Swanton C., Piccart M. Clinical management of breast cancer heterogeneity. Nature Rev. Clin. Oncol. 2015; 12 (7): 381–394. doi: 10.1038/nrclinonc.2015.73.
  7. Sagakyants A.B., Ulyanova E.P., Shulgina O.G., Zlatnik E.Yu., Novikova I.A., Karnaukhov N.S., Kuznetsova M.A., Vaschenko L.N., Petriashvili I.R., Lysenko E.P. Expression of tumor stem cell markers in regio­nal and distant breast cancer metastases. Modern Problems of Science and Education. 2020; (4): 128. (In Russ.) doi: 10.17513/spno.30045.
  8. Kolyadina I.V., Andreeva Yu.Yu., Frank G.A., Poddubnaya I.V. Role of bio­logical heterogeneity in recurrent and metastatic breast cancer. Arkhiv patologii. 2018; 80 (6): 62–67. (In Russ.) doi: 10.17116/patol20188006162.
  9. Konyshev K.V., Sazonov S.V. Her2-positive subtypes of the primary tumor in breast cancer often have heterogeneous metastases, whe­reas the triple-negative subtype of the tumor remains ­stable when metastasized. Vestnik ural'skoy meditsinskoy akademicheskoy nauki. 2020; 17 (4): 285–289. (In Russ.) doi: 10.22138/2500-0918-2020-17-4-285-289.
  10. Konyshev K.V., Sazonov S.V., Kazantseva N.V. Changes of the luminal A subtype of breast cancer in local metastasis. Virchows Archiv. 2020; 477 (Suppl. 1): S226. doi: 10.1007/s00428-020-02938-x.
  11. Konyshev K.V., Sazonov S.V. Study of her2/neu status of locoregionally metastasizing breast cancer cells in the cases with equivocal (2+) level of her2/neu oncoprotein expression in primary tumor tissue. Vestnik ural'skoy me­ditsinskoy akademicheskoy nauki. 2018; 15 (1): 48–54. (In Russ.) doi: 10.22138/2500-0918-2018-15-1-48-54.
  12. Konyshev K.V., Sazonov S.V. Changes of oestrogen receptor, progesterone receptor and Her2/neu statuses of localmetastases compared with primary tumour in breast cancer. Virchows Archiv. 2019; 475 (Suppl. 1): S84. doi: 10.1007/s00428-019-02631-8.
  13. Sazonov S.V., Konyshev K.V. Relationship of Her2/neu and oestrogen receptor changes in local metastases compared with primary tumour in breast cancer patients with equivocal (2+) Her2/neu expression level in primary tumour. Virchows Archiv. 2019; 475 (Suppl. 1): S91. doi: 10.1007/s00428-019-02631-8.
  14. Kolyadina I.V., Poddubnaya I.V., Van de Velde C.J.H., Kuppen P.J.K., Frank G.A., Komov D.V., Karseladze A.I., Bastiaannet E., Dekker-Ensink N.G. Immunological heterogeneity of stage I breast cancer: biological, population-based and prognostic ­value (international cooperation experience). Sovremennaya onkologiya. 2015; 17 (1): 30–38. (In Russ.)
  15. Carlsson J., Nordgren H., Sjöström J., Wester K., Villman K., Bengtsson N.O., Ostenstad B., Lundqvist H., Blomqvist C. HER2 expression in breast cancer primary tumours and corresponding metastases. Original data and literature review. Brit. J. Cancer. 2004; 90 (12): 2344–2348. doi: 10.1038/sj.bjc.6601881.
  16. Cui X., Schiff R., Arpino G., Osborne C.K., Lee A.V. Biology of progesterone receptor loss in breast cancer and its implications for endocrine therapy. J. Clin. Oncol. 2005; 23 (30): 7721–7735. doi: 10.1200/JCO.2005.09.004.
  17. Konyshev K.V., Brilliant A.A., Sazonov S.V. Ki67 level in primary tumor and locoregional metastases of breast cancer. Ural'skiy me­ditsinskiy zhurnal. 2015; 130 (7): 51–55. (In Russ.)
  18. Konyshev K.V., Brilliant A.A., Sazonov S.V. Change of estrogen receptor expression in breast cancer cells in locoregional metastases. Vestnik ural'skoy me­ditsinskoy akademicheskoy nauki. 2015; (2): 4–6. (In Russ.)
  19. Pectasides D., Gaglia A., Arapantoni-Dadioti P., Bobota A., Valavanis C., Kostopoulou V., Mylonakis N., Kara­belis A., Pectasides M., Economopoulos T. HER-2/neu status of primary breast cancer and corresponding metastatic sites in patients with advanced breast cancer treated with trastuzumab-based therapy. Anticancer Res. 2006; 26 (1B): 647–653. PMID: 16739334.
  20. Rosen P.P., Menendez-Botet C.J., Urban J.A., Fracchia A., Schwartz M.K. Estrogen receptor protein (ERP) in multiple tumor specimens from individual patients with breast cancer. Cancer. 1977; 39 (5): 2194–2200. doi: 10.1002/1097-0142(197705)39:5<2194::AID-CNCR2820390537>3.0.CO;2-Y.
  21. Liedtke C., Broglio K., Moulder S., Hsu L., Kau S.W., Symmans W.F., Albarracin C., Meric-Bernstam F., Woodward W., Theriault R.L., Kiesel L., Hortobagyi G.N., Pusztai L., Gonzalez-Angulo A.M. Prognostic impact of discordance between triple-receptor measurements in primary and recurrent breast cancer. Ann. Oncol. 2009; 20 (12): 1953–1958. doi: 10.1093/annonc/mdp263.
  22. Aitken S.J., Thomas J.S., Langdon S.P., Harrison D.J., Faratian D. Quantitative analysis of changes in ER, PR and HER2 expression in primary breast cancer and paired nodal metastases. Ann. Oncol. 2010; 21 (6): 1254–1261. doi: 10.1093/annonc/mdp427.
  23. Dawood S., Broglio K., Buzdar A.U., Hortobagyi G.N., Giordano S.H. 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. doi: 10.1200/JCO.2008.19.9844.
  24. Hoefnagel L.D.C., van de Vijver M.J., van Slo­oten H.-J., Wesseling P., Wesseling J., Westenend P.J., Bart J., Seldenrijk C.A., Nagtegaal I.D., Oudejans J., van der Valk P., van der Groep P., de Vries E.G.E., van der Wall E., van Diest P.J. Receptor conversion in distant breast cancer metastases. Breast Cancer Res. 2010; 12: R75. doi: 10.1186/bcr2645.
  25. Thompson A.M., Jordan L.B., Quinlan P., Anderson E., Skene A., Dewar J.A., Purdie C.A. Prospective comparison of switches in biomarker status between primary and recurrent breast cancer: the Breast Recurrence In Tissues Study (BRITS). Breast Cancer Res. 2010; 12: R92. doi: 10.1186/bcr2771.
  26. Gataullin I.G., Khasanov A.I., Khusainova G.N., Petrov S.V., Khasanov R.Sh. Rationale for optimal treatment of patients with metastatic breast cancer. Kubanskiy nauchnyy meditsinskiy vestnik. 2010; (9): 55–58. (In Russ.)
  27. Van Agthoven T., Timmermans M., Dorssers L.C.J., Henzen-Logmans S.C. Expression of estrogen, progeste­rone and epidermal growth factor receptors in primary and metastatic breast cancer. Intern. J. Cancer. 1995; 63 (6): 790–793. doi: 10.1002/ijc.2910630607.
  28. Amir E., Ooi W.S., Simmons C., Kahn H., Christakis M., Popovic S., Kalina M., Chesney A., Singh G., Clemons M. Discordance between receptor status in primary and metastatic breast cancer: An exploratory study of bone and bone marrow biopsies. Clin. Oncol. 2008; 20 (10): 763–768. doi: 10.1016/j.clon.2008.08.005.
  29. Holdaway I.M., Bowditch J.V. Variation in receptor status between primary and metastatic breast cancer. Cancer. 1983; 52 (3): 479–485. doi: 10.1002/1097-0142(19830801)52:3<479::AID-CNCR2820520317>3.0.CO;2-O.
  30. Hammond M.E.H., Hayes D.F., Dowsett M., Allred D.C., Hagerty K.L., Badve S., Fitzgibbons P.L., Francis G., Goldstein N.S., Hayes M., Hicks D.G., Lester S., Love R., Mangu P.B., McShane L., Miller K., Osborne C.K., Paik S., Perlmutter J., Rhodes A., Sasano H., Schwartz J.N., Sweep F.G.C., Taube S., Torlakovic E.E., Valenstein P., Viale G., Visscher D., Wheeler T., Williams R.B., Wittliff J.L., Wolff A.C. American Society of Clinical Oncology/College of American Pathologists guideline recommendations for immunohistochemical testing of estrogen and progesterone receptors in breast cancer. Arch. Pathol. Lab. Med. 2010; 134 (6): 907–1101. doi: 10.1200/JCO.2009.25.6529.
  31. Nishimura R., Osako T., Okumura Y., Tashima R., Toyozumi Y., Arima N. Changes in the ER, PgR, HER2, p53 and Ki-67 biological markers between primary and recurrent breast cancer: Discordance rates and prognosis. World J. Surg. Oncol. 2011; 9: 131. doi: 10.1186/1477-7819-9-131.
  32. Bogina G., Bortesi L., Marconi M., Venturini M., Lunardi G., Coati F., Massocco A., Manfrin E., Pegoraro C., Zamboni G. Comparison of hormonal receptor and HER-2 status between breast primary tumours and relap­sing tumours: Clinical implications of progesterone receptor loss. Virchows Arch. 2011; 459 (1): 1–10. doi: 10.1007/s00428-011-1097-7.
  33. Idirisinghe P.K., Thike A.A., Cheok P.Y., Tse G.M.-K., Lui P.C.-W., Fook-Chong S., Wong N.S., Tan P.H. Hormone receptor and c-ERBB2 status in distant metasta­tic and locally recurrent breast cancer: pathologic correlations and clinical significance. Am. J. Clin. Pathol. 2010; 133 (3): 416–429. doi: 10.1309/AJCPJ57FLLJRXKPV.
  34. Sari E., Guler G., Hayran M., Gullu I., Altundag K., Ozisik Y. Comparative study of the immunohistochemical detection of hormone receptor status and HER-2 expression in primary and paired recurrent/metastatic lesions of patients with breast cancer. Med. Oncol. 2011; 28 (1): 57–63. doi: 10.1007/s12032-010-9418-2.
  35. Lacroix H., Iglehart J.D., Skinner M.A., Kraus M.H. Overexpression of erbB-2 or EGF receptor proteins present in early stage mammary carcinoma is detected simultaneously in matched primary tumors and regional metastases. Oncogene. 1989; 4 (2): 145–151. PMID: 2564657.
  36. Tapia C., Savic S., Wagner U., Schönegg R., Novotny H., Grilli B., Herzog M., Barascud A.D., Zlobec I., Ca­thomas G., Terracciano L., Feichter G., Bubendorf L. HER2 gene status in primary breast cancers and matched distant metastases. Breast Cancer Res. 2007; 9 (3): R31. doi: 10.1186/bcr1676.
  37. Vincent-Salomon A., Pierga J.-Y., Couturier J., D’Enghien C.D., Nos C., Sigal-Zafrani B., Lae M., Fréneaux P., Diéras V., Thiéry J-P., Sastre-Garau X. HER2 status of bone marrow micrometastasis and their corresponding primary tumours in a pilot study of 27 ­cases: A possible tool for anti-HER2 therapy management? Bri­tish J. Cancer. 2007; 96 (4): 654–659. doi: 10.1038/sj.bjc.6603584.
  38. Cho E.Y., Han J.J., Choi Y.-L., Kim K.-M., Oh Y.L. Comparison of Her-2, EGFR and cyclin D1 in primary breast cancer and paired metastatic lymph nodes: An immunohistochemical and chromogenic in situ hybridization study. J. Korean Med. Sci. 2008; 23 (6): 1053–1061. doi: 10.3346/jkms.2008.23.6.1053.
  39. Pusztai L., Viale G., Kelly C.M., Hudis C.A. Estrogen and HER-2 receptor discordance between primary breast cancer and metastasis. Oncologist. 2010; 15 (11): 1164–1168. doi: 10.1634/theoncologist.2010-0059.
  40. Aoyama K., Kamio T., Nishikawa T., Kameoka S. A comparison of HER2/neu gene amplification and its protein overexpression between primary breast cancer and metastatic lymph nodes. Japanese J. Clin. Oncol. 2010; 40 (7): 613–619. doi: 10.1093/jjco/hyq019.
  41. Bozzetti C., Negri F.V., Lagrasta C.A., Crafa P., Bassano C., Tamagnini I., Gardini G., Nizzoli R., Leonardi F., Gasparro D., Camisa R., Cavalli S., Capelli S., Silini E.M., Ardizzoni A. Comparison of HER2 status in primary and paired metastatic sites of gastric carcinoma. British J. Cancer. 2011; 104 (9): 1372–1376. doi: 10.1038/bjc.2011.121.
  42. Chang H.J., Han S.-W., Oh D.-Y., Im S.-A., Jeon Y.K., Park I.A., Han W., Noh D.-Y., Bang Y.-J., Kim T.-Y. Discordant human epidermal growth factor receptor 2 and hormone receptor status in primary and metastatic breast cancer and response to trastuzumab. Japanese J. Clin. Oncol. 2011; 41 (5): 593–599. doi: 10.1093/jjco/hyr020.
  43. Fabi A., Di Benedetto A., Metro G., Perracchio L., Nisticò C., Di Filippo F., Ercolani C., Ferretti G., Melucci E., Buglioni S., Sperduti I., Papaldo P., Cognetti F., Mottolese M. HER2 protein and gene variation between primary and metastatic breast cancer: Significance and impact on patient care. Clin. Cancer Res. 2011; 17 (7): 2055–2064. doi: 10.1158/1078-0432.CCR-10-1920.
  44. Regitnig P., Schippinger W., Lindbauer M., Samonigg H., Lax S.F. Change of HER-2/neu status in a subset of distant metastases from breast carcinomas. J. Pathol. 2004; 203 (4): 918–926. doi: 10.1002/path.1592.
  45. Xiang J., Pan X., Xu J., Fu X., Wu D., Zhang Y., Shen L., Wei Q. Human epidermal growth factor receptor 2 protein expression between primary breast cancer and paired asynchronous local-regional recurrences. Experim. The­rap. Med. 2011; 2 (6): 1187–1191. doi: 10.3892/etm.2011.335.
  46. Xiao C., Gong Y., Han E.Y., Gonzalez-Angulo A.M., Sneige N. Stability of HER2-positive status in breast carcinoma: A comparison between primary and paired metasta­tic tumors with regard to the possible impact of intervening trastuzumab treatment. Ann. Oncol. 2011; 22 (7): 1547–1553. doi: 10.1093/annonc/mdq623.
  47. Zurrida S., Montagna E., Naninato P., Colleoni M., Goldhirsch A. Receptor status (ER, PgR and HER2) discordance between primary tumor and locoregional recurrence in breast cancer. Ann. Oncol. 2011; 22 (2): 479–480. doi: 10.1093/annonc/mdq688.
  48. Goldhirsch A., Winer E.P., Coates A.S., Gelber R.D., Piccart-Gebhart M., Thürlimann B. 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. doi: 10.1093/annonc/mdt303.
  49. Coates A.S., Winer E.P., Goldhirsch A., Gelber R.D., Gnant M., Piccart-Gebhart M. Tailoring therapies — improving the management of early breast cancer: St GallenInternational Expert Consensus on the Primary Therapy of Early Breast Cancer 2015. Ann. Oncol. 2015; 26 (8): 1533–1546. doi: 10.1093/annonc/mdv221.
  50. Buxant F., Anaf V., Simon P., Fayt I., Noël J.C. Ki-67 immunostaining activity is higher in positive axil­lary lymph nodes than in the primary breast tumor. Breast Cancer Res. Treat. 2002; 75 (1): 1–3. doi: 10.1023/A:1016504129183.
  51. D’Andrea M.R., Limiti M.R., Bari M., Zambenedetti P., Montagutti A., Ricci F., Pappagallo G.L., Sartori D., Vinante O., Mingazzini P.L. Correlation between gene­tic and biological aspects in primary non-metastatic breast cancers and corresponding synchronous axillary lymph node metastasis. Breast Cancer Res. Treat. 2007; 101 (3): 279–284. doi: 10.1007/s10549-006-9300-2.
  52. Ibrahim T., Farolfi A., Scarpi E., Mercatali L. Hormonal receptor, human epidermal growth factor receptor-2, and Ki67 discordance between primary breast cancer and paired metastases: Clinical impact. Oncology. 2013; 84 (3): 150–157. doi: 10.1159/000345795.
  53. Paksoy S.E., Tasdelen I., Balaban A.S., Ozkaya G., Tolunay S. A comparison of Ki67 proliferative index in primary tumor and axillary metastatic lymph nodes with length of survival in patients with breast cancer. Bratislavské lekárske listy. 2013; 114 (11): 645–649. doi: 10.4149/bll_2013_138.
  54. Rossi S., Basso M., Strippoli A., Daddu­zio V., Cerchiaro E., Barile R., D'Argento E., Cassano A., Schinzari G., Barone C. Hormone receptor status and HER2 expression in primary breast cancer compared with synchronous axillary metastases or recurrent metastatic disease. Clin. Breast Cancer. 2015; 15 (5): 307–312. doi: 10.1016/j.clbc.2015.03.010.
  55. Raica M., Cîmpean A.M., Ceausu R.A., Fulga V., Nica C., Rudico L., Saptefrati L. Hormone receptors and HER2 expression in primary breast carcinoma and corresponding lymph node metastasis: Do we need both? Anticancer Res. 2014; 34 (3): 1435–1440. PMID: 24596391.
  56. Falck A.K., Bendahl P.O., Chebil G., Olsson H., Fernö M., Rydén L. Biomarker expression and St Gallen molecular subtype classification in primary tumours, synchronous lymph node metastases and asynchronous relapses in primary breast cancer patients with 10 years’ follow-up. Breast Cancer Res. Treat. 2013; 140 (1): 93–104. doi: 10.1007/s10549-013-2617-8.
  57. Pak D.D., Rasskazova E.A., Danilova T.V. Subtypes of breast cancer. Opukholi zhenskoy reproduktivnoy sistemy. 2012; (3–4): 13–19. (In Russ.)
  58. Falck A.-K., Fernö M., Bendahl P.-O., Rydén L. St Gallen molecular subtypes in primary breast cancer and matched lymph node metastases — aspects on distribution and prognosis for patients with luminal A tumours: Results from a prospective randomised trial. BMC Cancer. 2013; 13: 558. doi: 10.1186/1471-2407-13-558.
  59. Ufen M.-P., Kohne C.H., Wischneswky M., Wol­ters R., Novopashenny I., Fischer J., Constantinidou M., Possinger K., Regierer A.C. Metastatic breast cancer: are we treating the same patients as in the past? Ann. Oncol. 2013; 25 (1): 95–100. doi: 10.1093/annonc/mdt429.
  60. Aurilio G., Monfardini L., Rizzo S., Sciandivasci A., Preda L., Bagnardi V., Disalvatore D., Pruneri G., Munzone E., Della Vigna P., Renne G., Bellomi M., Curigliano G., Goldhirsch A., Nolè F. Discordant hormone receptor and human epidermal growth factor receptor 2 status in bone metastases compared to primary breast cancer. Acta Oncologica. 2013; 52: 1649–1656. doi: 10.3109/0284186X.2012.754990.
  61. Khasraw M., Brogi E., Seidman A.D. The need to exa­mine metastatic tissue at the time of progression of breast cancer: is re-biopsy a necessity or a luxury? Curr. Oncol. Rep. 2011; 13 (1): 17–25. doi: 10.1007/s11912-010-0137-9.
  62. Zardavas D., Irrthum A., Swanton C., Piccart M. Clinical management of breast cancer heterogeneity. Nature Rev. Clin. Oncol. 2015; 12 (7): 381–394. doi: 10.1038/nrclinonc.2015.73.
  63. Niikura N., Liu J., Hayashi N., Mittendorf E.A., Gong Y., Palla S.L., Tokuda Y., Gonzalez-Angulo A.M., Hortobagyi G.N., Ueno N.T. Loss of human epidermal growth factor receptor 2 (HER2) expression in meta­static sites of HER2-overexpressing primary breast tumors. J. Clin. Oncol. 2012; 30 (6): 593–599. doi: 10.1200/JCO.2010.33.8889.
  64. Dieci M.V., Barbieri E., Piacentini F., Ficarra G., Bettelli S., Dominici M., Conte P.F., Guarneri V. Discordance in receptor status between primary and recurrent breast cancer has a prognostic impact: A single-institution analysis. Ann. Oncol. 2013; 24 (1): 101–108. doi: 10.1093/annonc/mds248.
  65. Amir E., Miller N., Geddie W., Freedman O., Kassam F., Simmons C., Oldfield M., Dranitsaris G., Tomlinson G., Laupacis A., Tannock I.F., Clemons M. Prospective study evaluating the impact of tissue confirmation of me­tastatic disease in patients with breast cancer. J. Clin. Oncol. 2012; 30 (6): 587–592. doi: 10.1200/JCO.2010.33.5232.
  66. Petrov S.V. The capabilities and limitations of immunohistochemical ana­lysis in clinical oncology. Ural'skiy meditsinskiy zhurnal. 2014; (8): 5–9. (In Russ.)
  67. Ieni A., Barresi V., Caltabiano R., Cascone A.M., Del Sordo R., Cabibi D., Zeppa P., Lanzafame S., Sidoni A., Franco V., Tuccari G. Discordance rate of HER2 status in primary breast carcinomas versus synchronous axil­lary lymph node metastases: A multicenter retrospective investigation. Onco Targets Ther. 2014; 7: 1267–1272. doi: 10.2147/OTT.S65294.
  68. Kaufman P.A., Bloom K.J., Burris H., Gralow J.R., Mayer M., Pegram M., Rugo H.S., Swain S.M., Yardley D.A., Chau M., Lalla D., Yoo B., Brammer M.G., Vogel C.L. Assessing the discordance rate between local and central HER2 testing in women with locally determined HER2-negative breast cancer. Cancer. 2014; 120 (17): 2657–2664. doi: 10.1002/cncr.28710.
  69. Sighoko D., Liu J., Hou N., Gustafson P., Huo D. Discordance in hormone receptor status among primary, metastatic, and second primary breast cancers: biological difference or misclassification? Oncologist. 2014; 19 (6): 592–601. doi: 10.1634/theoncologist.2013-0427.
  70. Cardoso F., Harbeck N., Fallowfield L., Kyria­kides S., Senkus E. Locally recurrent or metastatic breast cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann. Oncol. 2012; 23 (Suppl. 7): VII11– VII19. doi: 10.1093/annonc/mds232.
  71. Wolff A.C., Hammond M.E.H., Hicks D.G., Dowsett M., McShane L.M., Allison K.H. 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. Arch. Pathol. Lab. Med. 2014; 138 (2): 241–256. doi: 10.5858/arpa.2013-0953-SA.
  72. «Золотой стандарт» диагностики и лечения рака молочной железы 2021. М.: АБВ-пресс. 2020; 23–28. [“Zolotoy standart” diagnostiki i lecheniya raka molochnoy zhelezy 2021. (Golden standard of breast cancer diagnostics and threatment 2021.) M.: ABV-press. 2020; 23–28. (In Russ.)]
  73. Konyshev K.V., Sazonov S.V., Leont'ev S.L. Izmenenie retseptornogo apparata kletok kartsinomy molochnoy zhelezy pri regionarnom metastazirovanii. (Changes in the receptor apparatus of breast carcinoma cells during regional metastasis.) Yekaterinburg: Redaktsiya zhurnala “Vestnik Ural'skoy meditsinskoy akademicheskoy nauki”. 2019; 88–92. (In Russ.)

© 2021 Eco-Vector

This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies