Panchenko IS, Panchenko SV, Sharafutdinov MG, Rodionov VV, Kometova VV, Burmenskaya OV. Prognostic significance of androgen receptor expression in triple-negative breast cancer. Journal of Modern Oncology. 2024;26(4):426–430. DOI: 10.26442/18151434.2024.4.202919
Прогностическая значимость экспрессии рецепторов андрогенов при трижды негативном раке молочной железы
Panchenko IS, Panchenko SV, Sharafutdinov MG, Rodionov VV, Kometova VV, Burmenskaya OV. Prognostic significance of androgen receptor expression in triple-negative breast cancer. Journal of Modern Oncology. 2024;26(4):426–430. DOI: 10.26442/18151434.2024.4.202919
Обоснование. Определение экспрессии рецепторов андрогенов (АР) при трижды негативном раке молочной железы (ТНРМЖ) является перспективной задачей онкологии. Цель. Выявить корреляцию экспрессии АР с клиническими и генетическими характеристиками опухоли и прогнозом заболевания. Материалы и методы. В исследование вошли 246 человек с ТНРМЖ, проходивших лечение в ГУЗ ОКОД (г. Ульяновск) и ФГБУ «НМИЦ АГП им. акад. В.И. Кулакова» (г. Москва) в период с 2014 по 2024 г. У всех пациентов определяли степень экспрессии АР иммуногистохимическим методом. Анализировали клинические (возраст, размер первичной опухоли, число пораженных регионарных лимфатических узлов, значение суммарного балла злокачественности) и генетические (уровень экспрессии 44 различных генов, выраженных в ln-шкале) параметры опухоли. Для оценки взаимосвязи между экспрессией АР и клинико-генетическими параметрами использовали параметрические (t-критерий Стьюдента) и непараметрические (однофакторный дисперсионный анализ) методы статистики. Для определения прогноза проводили анализ общей выживаемости с помощью построения кривых Каплана–Мейера. Результаты. При сравнении кривых выживаемости использовался лог-ранговый критерий. Различия между группами считали статистически значимыми при р<0,05. Экспрессия АР ассоциируется с пожилым возрастом, метастатическим поражением регионарных лимфатических узлов, с экспрессией CTSL2, AURKA, KRT5, CCND1, BCL2, FGFR4, TMEM45A, MiKI67, MYBL2, CDKN2A, FOXA1, SFRP1, PTEN, CD68, EMSY, GATA3, EXO1, PPP2R2A, TPX2, PAK1, PTTG1, UBE2T, KIF14, CCNB1, BAG1, TMEM45B, MYC, MIA, BIRC5, PD-L1, TRAC, ZNF703, TYMS, CCNE, ANLN и неблагоприятным отдаленным прогнозом при ТНРМЖ. Заключение. ТНРМЖ с наличием экспрессии АР является неоднородным подтипом. Он ассоциируется с пожилым возрастом, метастатическим поражением регионарных лимфатических узлов, а также экспрессией большого числа генов. Согласно нашим данным экспрессия АР при ТНРМЖ ассоциируется с неблагоприятным отдаленным прогнозом данной категории пациентов.
Ключевые слова: рецепторы андрогенов, трижды негативный рак молочной железы
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Background. Determining androgen receptor (AR) expression in triple-negative breast cancer (TNBC) is a promising tool in oncology. Aim. To identify the correlation of AR expression with the clinical and genetic characteristics of the tumor and the disease prognosis. Materials and methods. The study included 246 subjects with TNBC treated at Ulyanovsk Regional Oncological Clinical Dispensary and Kulakov National Medical Research Center for Obstetrics, Gynecology, and Perinatology (Moscow) from 2014 to 2024. The AR expression was determined by immunohistochemical method in all patients. Clinical (age, primary tumor size, number of regional lymph nodes affected, total malignancy score) and genetic (expression level of 44 genes expressed on the ln-scale) tumor parameters were analyzed. Parametric (Student's t-test) and non-parametric (one-way ANOVA) statistical methods were used to evaluate the relationship between AR expression and clinical genetic parameters. An overall survival analysis was performed using Kaplan–Meier curves to determine the prognosis. Results. A log-rank test was used when comparing survival curves. Differences between groups were considered statistically significant at p<0.05. AR expression is associated with elderly age, metastatic lesions of regional lymph nodes, with the expression of CTSL2, AURKA, KRT5, CCND1, BCL2, FGFR4, TMEM45A, MiKI67, MYBL2, CDKN2A, FOXA1, SFRP1, PTEN, CD68, EMSY, GATA3, EXO1, PPP2R2A, TPX2, PAK1, PTTG1, UBE2T, KIF14, CCNB1, BAG1, TMEM45B, MYC, MIA, BIRC5, PD-L1, TRAC, ZNF703, TYMS, CCNE, ANLN and poor long-term prognosis in TNBC. Conclusion. TNBC with AR expression is a heterogeneous subtype. It is associated with advanced age, metastatic involvement of regional lymph nodes, and expression of a large number of genes. According to our data, AR expression in TNBC is associated with unfavorable long-term prognosis of this category of patients.
Keywords: androgen receptors, triple-negative breast cancer
1. Li X, Yang J, Peng L, et al. Triple-negative breast cancer has worse overall survival and cause-specific survival than non-triple-negative breast cancer. Breast Cancer Res Treat. 2017;161(2):279-87. DOI:10.1007/s10549-016-4059-6
2. Kennecke H, Yerushalmi R, Woods R, et al. Metastatic behavior of breast cancer subtypes. J Clin Oncol. 2010;28(20):3271-7. DOI:10.1200/JCO.2009.25.9820
3. Grasset EM, Dunworth M, Sharma G, et al. Triple-negative breast cancer metastasis involves complex epithelial-mesenchymal transition dynamics and requires vimentin. Sci Transl Med. 2022;14(656):eabn7571. DOI:10.1126/scitranslmed.abn7571
4. Astvatsaturyan K, Yue Y, Walts AE, Bose S. Androgen receptor positive triple negative breast cancer: Clinicopathologic, prognostic, and predictive features. PLoS One. 2018;13(6):e0197827. DOI:10.1371/journal.pone.0197827
5. Burstein MD, Tsimelzon A, Poage GM, et al. Comprehensive genomic analysis identifies novel subtypes and targets of triple-negative breast cancer. Clin Cancer Res. 2015;21(7):1688-98. DOI:10.1158/1078-0432.CCR-14-0432
6. Grellety T. Cancer du sein triple négatif exprimant le récepteur aux androgènes: de la biologie à la thérapeutique [Androgen receptor-positive triple negative breast cancer: From biology to therapy]. Bull Cancer. 2020;107(4):506-16 [French]. DOI:10.1016/j.bulcan.2019.12.012
7. 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(1):82-9. DOI:10.1245/s10434-014-3984-z
8. Bonnefoi H, Grellety T, Tredan O, et al. A phase II trial of abiraterone acetate plus prednisone in patients with triple-negative androgen receptor positive locally advanced or metastatic breast cancer (UCBG 12-1). Ann Oncol. 2016;27(5):812-8. DOI:10.1093/annonc/mdw067
9. Kometova V, Panchenko I, Rodionov V, et al. The scale of androgen expression in triple negative breast cancer. Abstracts 29-th European Congress of Pathology: Pathology for Patient Care. – RAI Amsterdam, The Netherlands, 02.09–06.09.2017. – PS-01-018 (S54). Virchows Arch. 2017;471(Suppl. 1):68-9.
10. Luo X, Shi YX, Li ZM, Jiang WQ. Expression and clinical significance of androgen receptor in triple negative breast cancer. Chin J Cancer. 2010;29(6):585-90. DOI:10.5732/cjc.009.10673
11. Pistelli M, Caramanti M, Biscotti T, et al. Androgen receptor expression in early triple-negative breast cancer: clinical significance and prognostic associations. Cancers (Basel). 2014;6(3):1351-62. DOI:10.3390/cancers6031351
12. Gasparini P, Fassan M, Cascione L, et al. Androgen receptor status is a prognostic marker in non-basal triple negative breast cancers and determines novel therapeutic options. PLoS One. 2014;9(2):e88525. DOI:10.1371/journal.pone.0088525
13. Qiu P, Guo Q, Yao Q, et al. Hsa-mir-3163 and CCNB1 may be potential biomarkers and therapeutic targets for androgen receptor positive triple-negative breast cancer. PLoS One. 2021;16(11):e0254283. DOI:10.1371/journal.pone.0254283
14. Wang Y, Hacking SM, Li Z, et al. Triple-negative Breast Carcinoma With Apocrine and Histiocytoid Features: A Clinicopathologic and Molecular Study of 18 Cases. Am J Surg Pathol. 2023;47(9):1011-8. DOI:10.1097/PAS.0000000000002073
15. Guiu S, Charon-Barra C, Vernerey D, et al. Coexpression of androgen receptor and FOXA1 in nonmetastatic triple-negative breast cancer: ancillary study from PACS08 trial. Future Oncol. 2015;11(16):2283-97. DOI:10.2217/fon.15.102
16. Chartier S, Brochard C, Martinat C, et al. TROP2, androgen receptor, and PD-L1 status in histological subtypes of high-grade metaplastic breast carcinomas. Histopathology. 2023;82(5):664-71. DOI:10.1111/his.14852
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1. Li X, Yang J, Peng L, et al. Triple-negative breast cancer has worse overall survival and cause-specific survival than non-triple-negative breast cancer. Breast Cancer Res Treat. 2017;161(2):279-87. DOI:10.1007/s10549-016-4059-6
2. Kennecke H, Yerushalmi R, Woods R, et al. Metastatic behavior of breast cancer subtypes. J Clin Oncol. 2010;28(20):3271-7. DOI:10.1200/JCO.2009.25.9820
3. Grasset EM, Dunworth M, Sharma G, et al. Triple-negative breast cancer metastasis involves complex epithelial-mesenchymal transition dynamics and requires vimentin. Sci Transl Med. 2022;14(656):eabn7571. DOI:10.1126/scitranslmed.abn7571
4. Astvatsaturyan K, Yue Y, Walts AE, Bose S. Androgen receptor positive triple negative breast cancer: Clinicopathologic, prognostic, and predictive features. PLoS One. 2018;13(6):e0197827. DOI:10.1371/journal.pone.0197827
5. Burstein MD, Tsimelzon A, Poage GM, et al. Comprehensive genomic analysis identifies novel subtypes and targets of triple-negative breast cancer. Clin Cancer Res. 2015;21(7):1688-98. DOI:10.1158/1078-0432.CCR-14-0432
6. Grellety T. Cancer du sein triple négatif exprimant le récepteur aux androgènes: de la biologie à la thérapeutique [Androgen receptor-positive triple negative breast cancer: From biology to therapy]. Bull Cancer. 2020;107(4):506-16 [French]. DOI:10.1016/j.bulcan.2019.12.012
7. 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(1):82-9. DOI:10.1245/s10434-014-3984-z
8. Bonnefoi H, Grellety T, Tredan O, et al. A phase II trial of abiraterone acetate plus prednisone in patients with triple-negative androgen receptor positive locally advanced or metastatic breast cancer (UCBG 12-1). Ann Oncol. 2016;27(5):812-8. DOI:10.1093/annonc/mdw067
9. Kometova V, Panchenko I, Rodionov V, et al. The scale of androgen expression in triple negative breast cancer. Abstracts 29-th European Congress of Pathology: Pathology for Patient Care. – RAI Amsterdam, The Netherlands, 02.09–06.09.2017. – PS-01-018 (S54). Virchows Arch. 2017;471(Suppl. 1):68-9.
10. Luo X, Shi YX, Li ZM, Jiang WQ. Expression and clinical significance of androgen receptor in triple negative breast cancer. Chin J Cancer. 2010;29(6):585-90. DOI:10.5732/cjc.009.10673
11. Pistelli M, Caramanti M, Biscotti T, et al. Androgen receptor expression in early triple-negative breast cancer: clinical significance and prognostic associations. Cancers (Basel). 2014;6(3):1351-62. DOI:10.3390/cancers6031351
12. Gasparini P, Fassan M, Cascione L, et al. Androgen receptor status is a prognostic marker in non-basal triple negative breast cancers and determines novel therapeutic options. PLoS One. 2014;9(2):e88525. DOI:10.1371/journal.pone.0088525
13. Qiu P, Guo Q, Yao Q, et al. Hsa-mir-3163 and CCNB1 may be potential biomarkers and therapeutic targets for androgen receptor positive triple-negative breast cancer. PLoS One. 2021;16(11):e0254283. DOI:10.1371/journal.pone.0254283
14. Wang Y, Hacking SM, Li Z, et al. Triple-negative Breast Carcinoma With Apocrine and Histiocytoid Features: A Clinicopathologic and Molecular Study of 18 Cases. Am J Surg Pathol. 2023;47(9):1011-8. DOI:10.1097/PAS.0000000000002073
15. Guiu S, Charon-Barra C, Vernerey D, et al. Coexpression of androgen receptor and FOXA1 in nonmetastatic triple-negative breast cancer: ancillary study from PACS08 trial. Future Oncol. 2015;11(16):2283-97. DOI:10.2217/fon.15.102
16. Chartier S, Brochard C, Martinat C, et al. TROP2, androgen receptor, and PD-L1 status in histological subtypes of high-grade metaplastic breast carcinomas. Histopathology. 2023;82(5):664-71. DOI:10.1111/his.14852
1ФГБОУ ВО «Ульяновский государственный университет», Ульяновск, Россия; 2ГУЗ «Областной клинический онкологический диспансер», Ульяновск, Россия; 3ФГБУ «Национальный медицинский исследовательский центр акушерства, гинекологии и перинатологии им. акад. В.И. Кулакова» Минздрава России, Москва, Россия
*pan91ch@yandex.ru
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Ivan S. Panchenko*1,2, Sergei V. Panchenko1,2, Marat G. Sharafutdinov1, Valerii V. Rodionov3, Vlada V. Kometova3, Olga V. Burmenskaya3
1Ulyanovsk State University, Ulyanovsk, Russia; 2Regional Clinical Oncologic Dispensary, Ulyanovsk, Russia; 3Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Moscow, Russia
*pan91ch@yandex.ru