Expresión de receptores de andrógeno en pacientes con carcinoma de mama del subtipo triple negativo.
Expression of androgen receptors in patients with triple-negative subtype breast carcinoma.
Keywords:
breast carcinoma, triple negative, androgen receptor, immunohistochemistry
Abstract
Breast carcinoma of the triple-negative subtype (TNBC) does not express estrogen, progesterone or human epidermal growth factor receptor 2 (HER2) receptors. A subclassification of TNBC has been proposed into four subgroups, one of which is the luminal androgen receptor. The objective of this work was to determine the expression of the androgen receptor (AR) in women with TNBC, diagnosed by immunohistochemistry, at the Hospital Metropolitano del Norte, Valencia, Venezuela. The sample consisted of 191 patients who met the inclusion criteria. The mean age of the patients at the time of diagnosis was 54.91 years. Histologically, the majority of the tumors were moderately differentiated or undifferentiated. The percentage of AR expression was 22% (42 of 191). In the association between AR expression and the Ki-67 proliferative index, a greater number of AR positive cases was observed in tumors with Ki-67 expression of less than 40%. The AR positivity found in this study represents an intermediate frequency in relation to other investigations. No statistically significant differences were found with the age of the patients and histological grade of the tumors, while the Ki-67 proliferative index was lower for AR+ tumors, compared to TNBC in general.
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References
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McGhan L, McCullough A, Protheroe C, Dueck A, Lee J, Nunez R, Castle E, Gray R, Wasif N, Goetz M, Hawse J, Henry T, Barrett M, Cunliffe H, Pockaj B. Androgen receptor-positive triple negative breast cancer: a unique breast cancer subtype. Ann Surg Oncol 2014; 21:361-367. https://doi.org/10.1245/s10434-013-3260-7.
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Hu XQ, Chen WL, Ma HG, Jiang K. Androgen receptor expression identifies patient with favorable outcome in operable triple negative breast cancer. Oncotarget 2017; 8:56364-56374. https://doi.org/10.18632/oncotarget.16913.
Mohammed AA, Elsayed FM, Algazar M, Rashed HE, Anter AH. Neoadjuvant chemotherapy in triple negative breast cancer: correlation between androgen receptor expression and pathological response. Asian Pac J Cancer Pre. 2020; 21:563-568. https://doi.org/10.31557/APJCP.2020.21.2.563.
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Martínez A, Lozano A, Rodríguez A, Galindo O, Alvarado S. Breast cancer and mastectomy’s psychological impact. Gac Mex Oncol 2014; 13:53-58.
Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2021; 71:209-249. https://doi.org/10.3322/caac.21660.
Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D, Bray F. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer 2015; 136: E359-86. https://doi. org/10.1002/ijc.29210.
Ferlay J, Colombet M, Soerjomataram I, Mathers C, Parkin DM, Piñeros M, Znaor A, Bray F. Estimating the global cancer incidence and mortality in 2018: GLOBOCAN sources and methods. Int J Cancer 2019; 144:1941-1953. https://doi. org/10.1002/ijc.31937.
Fernández-Tortolero Á, Reigosa-Yániz Subtypes of luminal breast carcinoma according to the Saint Gallen Consensus in a group of Venezuelan patients. Bio-medica. 2021; 41:531-540. https://doi. org/10.7705/biomedica.5496.
Bergin ART, Loi S. Triple-negative breast cancer: recent treatment advances. F1000Res 2019; 8:F1000. https://doi.org/ 10.12688/f1000research.18888.1.
Lehmann BD, Bauer JA, Chen X, Sanders ME, Chakravarthy AB, Shyr Y, Pietenpol JA. Identification of human triple-negative breast cancer subtypes and preclinical models for selection of targeted therapies. J Clin Invest 2011; 121:2750-2767. https://doi.org/10.1172/JCI45014.
Burstein MD, Tsimelzon A, Poage GM, Covington KR, Contreras A, Fuqua SA, Savage MI, Osborne CK, Hilsenbeck SG, Chang JC, Mills GB, Lau CC, Brown PH. Comprehensive genomic analysis identifies novel subtypes and targets of triple-negative breast cancer. Clin Cancer Res 2015; 21:1688-698. https://doi.org/10.1158/1078-0432.CCR-14-0432.
Camargo A, Tamburelli M, Frahm I, Barreto M, Bianchi F, Dávalos J, Castaño R. ¿Es posible identificar factores pronósticos y predictivos en cáncer de mama triple negativo? Rev Arg Mastol 2018; 36:27-41.
Gasparini P, Fassan M, Cascione L, Guler G, Balci S, Irkkan C, Paisie C, Lovat F, Morrison C, Zhang J, Scarpa A, Croce CM, Shapiro CL, Huebner K. Androgen receptor status is a prognostic marker in non-basal triple negative breast cancers and determines novel therapeutic options. PLoS One 2014; 9: e88525. https://doi.org/10.1371/journal.pone.0088525.
Xu M, Yuan Y, Yan P, Jiang J, Ma P, Niu X, Ma S, Cai H, Yang K. Prognostic significance of androgen receptor expression in triple negative breast cancer: A Systematic review and meta-analysis. Clin Breast Cancer 2020; 20:385-396. https://doi.org/10.1016/j.clbc.2020.01.002.
Gerratana L, Basile D, Buono G, De Placido S, Giuliano M, Minichillo S, Coinu A, Martorana F, De Santo I, Del Mastro L, De Laurentiis M, Puglisi F, Arpino G. Androgen receptor in triple negative breast cancer: A potential target for the targetless subtype. Cancer Treat Rev 2018; 68:102-110. https://doi.org/10.1016/j.ctrv.2018.06.005.
Anestis A, Zoi I, Papavassiliou AG, Karamouzis MV. Androgen receptor in breast cancer-clinical and preclinical research in-sights. Molecules. 2020; 25:358. https://doi.org/10.3390/molecules25020358.
Lamb CA, Vanzulli SI, Lanari C. Hormone receptors in breast cancer: more than estrogen receptors. Medicina (B Aires) 2019; 79:540-545.
Zaharia M, Gomez H. Cáncer de mama triple negativo: una enfermedad de difícil diagnóstico y tratamiento. Rev Peru Med Exp Salud Pública 2013; 30:649-656.
Lee A, Djamgoz M. Triple negative breast cancer: Emerging therapeutic modalities and novel combination therapies. Cancer Treat Rev 2018; 62:110-122. https://doi.org/10.1016/j.ctrv.2017.11.003.
Reigosa A, Caleiras E, Castro J, Saldivia F, Romero R, Domínguez Y, Castillo L, Fernández A. Subtipos moleculares del carcinoma de mama en región central de Venezuela. Rev Venez de Oncol 2021; 33:176-186.
Reigosa A, Hardisson D, Sanz F, Caleiras E, Saldivia F, Fernández A. Subclasificación de los tipos moleculares de cáncer de mama de acuerdo a la expresión de marcadores inmunohistoquímicos y evolución. Invest Clin 2016; 57:188-218.
Yang R, Li Y, Wang H, Qin T, Yin X, Ma X. Therapeutic progress and challenges for triple negative breast cancer: targeted therapy and immunotherapy. Mol Bio-med 2022; 3:8. https://doi.org/10.1186/s43556-022-00071-6.
Sharma P. Biology and management of patients with triple-negative breast cancer. Oncologist 2016; 21:1050-62. https://doi.org/10.1634/theoncologist.2016-0067.
Yin L, Duan JJ, Bian XW, Yu SC. Triple-negative breast cancer molecular subtyping and treatment progress. Breast Cancer Res 2020; 22:61. https://doi.org/10.1186/ s13058-020-01296-5.
Barton VN, D’Amato NC, Gordon MA, Christenson JL, Elias A, Richer JK. Androgen receptor biology in triple negative breast cancer: a case for classification as AR+ or quadruple negative disease. Horm Cancer 2015; 6:206-213. https://doi.org/10.1007/s12672-015-0232-3.
Bhattarai S, Klimov S, Mittal K, Krishnamurti U, Li X, OpreaIlies G, Wetherilt C, Riaz A, Aleskandarany M, Green A, Ellis I, Cantuaria G, Gupta M, Manne U, Agboola J, Baskovich B, Janssen EAM, Callagy G, Walsh EM, Mehta A, Dogra A, Shet T, Gajaria P, Traina T, Nggada H, Omonisi A, Ahmed S, Rakha E, Rida P, Aneja R. Prognostic role of androgen receptor in triple negative breast cancer: a multi-institutional study. Cancers 2019; 11:995. https://doi.org/10.3390/cancers11070995.
Melo M, Serrano S, Abaunza M. Androgen receptor expression and prognosis in Hispanic/Latino women with triple negative breast cancer. Rev Esp Patol 2022; 55:96-104.
McGhan L, McCullough A, Protheroe C, Dueck A, Lee J, Nunez R, Castle E, Gray R, Wasif N, Goetz M, Hawse J, Henry T, Barrett M, Cunliffe H, Pockaj B. Androgen receptor-positive triple negative breast cancer: a unique breast cancer subtype. Ann Surg Oncol 2014; 21:361-367. https://doi.org/10.1245/s10434-013-3260-7.
Astvatsaturyan K, Yue Y, Walts AE, Bose S. Androgen receptor positive triple negative breast cancer: Clinicopathologic, prognostic, and predictive features. PLoS One 2018; 13:e0197827. https://doi.org/10.1371/journal.pone.0197827.
Choi JE, Kang SH, Lee SJ, Bae YK. Androgen receptor expression predicts decreased survival in early stage triple-negative breast cancer. Ann Surg Oncol 2015; 22:82-89. https://doi.org/10.1245/s10434-014-3984-z.
Jam S, Abdollahi A, Zand S, Khazaeipour Z, Omranipour R, Najafi M. Androgen receptor expression in triple-negative breast cancer. Arch Breast Cancer 2019; 6:92-95.
Sunar V, T Dogan H, Sarici F, Ates O, Akin S, Baspinar B, Aksoy S, Altundag K. Association between androgen receptor status and prognosis in triple negative breast cancer. J BUON. 2018; 23:1325-1330.
Andre F, Arnedos M, Goubar A, Ghouadni A, Delaloge S. Ki-67--no evidence for its use in node-positive breast cancer. Nat Rev Clin Oncol 2015; 12:296-301. https://doi. org/10.1038/nrclinonc.2015.46.
Zhu X, Chen L, Huang B, Wang Y, Ji L, Wu J, Di G, Liu G, Yu K, Shao Z, Wang Z. The prognostic and predictive potential of Ki-67 in triple-negative breast cancer. Sci Rep 2020; 10:225. https://doi.org/10.1038/s41598-019-57094-3.
Zhao S, Ma D, Xiao Y, Li XM, Ma JL, Zhang H, Xu XL, Lv H, Jiang WH, Yang WT, Jiang YZ, Zhang QY, Shao ZM. Molecular subtyping of triple-negative breast cancers by immunohistochemistry: Molecular basis and clinical relevance. Oncologist 2020;25: e1481-e1491. https://doi.org/10.1634/theoncologist.2019-0982.
Kim S, Moon BI, Lim W, Park S, Cho MS, Sung SH. Feasibility of classification of triple negative breast cancer by immunohis-tochemical surrogate markers. Clin Breast Cancer 2018; 18:e1123-e1132. https://doi.org/10.1016/j.clbc.2018.03.012.
Santonja A, Sánchez-Muñoz A, Lluch A, Chica-Parrado MR, Albanell J, Chacón JI, Antolín S, Jerez JM, de la Haba J, de Luque V, Fernández-De Sousa CE, Vicioso L, Plata Y, Ramírez-Tortosa CL, Álvarez M, Llácer C, Zarcos-Pedrinaci I, Carrasco E, Caballero R, Martín M, Alba E. Triple negative breast cancer subtypes and pathologic complete response rate to neoadjuvant chemotherapy. Oncotarget 2018; 9:26406-26416. https://doi.org/10.18632/oncotar- get.25413.
McNamara KM, Yoda T, Miki Y, Nakamura Y, Suzuki T, Nemoto N, Miyashita M, Nishimura R, Arima N, Tamaki K, Ishida T, Ohuchi N, Sasano H. Androgen receptor and enzymes in lymph node metastasis and cancer reoccurrence in triple-negative breast cancer. Int J Biol Markers 2015; 30: e184-89. https://doi.org/10.5301/jbm.5000132.
Abd-Elazeem MA, Abd-Elazeem MA. Claudin 4 expression in triple-negative breast cancer: Correlation with androgen receptors and Ki-67 expression. Ann Diagn Pathol 2015; 19:37-42. https://doi. org/10.1016/j.anndiagpath.2014.10.003.
Hu XQ, Chen WL, Ma HG, Jiang K. Androgen receptor expression identifies patient with favorable outcome in operable triple negative breast cancer. Oncotarget 2017; 8:56364-56374. https://doi.org/10.18632/oncotarget.16913.
Mohammed AA, Elsayed FM, Algazar M, Rashed HE, Anter AH. Neoadjuvant chemotherapy in triple negative breast cancer: correlation between androgen receptor expression and pathological response. Asian Pac J Cancer Pre. 2020; 21:563-568. https://doi.org/10.31557/APJCP.2020.21.2.563.
Dieci MV, Tsvetkova V, Griguolo G, Miglietta F, Mantiero M, Tasca G, Cumerlato E, Giorgi CA, Giarratano T, Faggioni G, Falci C, Vernaci G, Menichetti A, Mioranza E, Di Liso E, Frezzini S, Saibene T, Orvieto E, Guarneri V. Androgen receptor expression and association with distant disease-free survival in triple negative breast cancer: Analysis of 263 patients treated with standard therapy for stage I-III disease. Front Oncol 2019; 9:452. https://doi.org/10.3389/fonc.2019.00452.
Published
2024-02-15
How to Cite
Hung, A., Gutiérrez, J., Gasia, J., Gil, Y., Guanipa, J., Castro , J., Reigosa, A., & Fernández, Ángel. (2024). Expresión de receptores de andrógeno en pacientes con carcinoma de mama del subtipo triple negativo.: Expression of androgen receptors in patients with triple-negative subtype breast carcinoma. Investigación Clínica, 65(1), 59-69. https://doi.org/10.54817/IC.v65n1a06
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