Expression of epidermal growth factor receptor in triple-negative breast cancer and its correlation with clinicopathologic features：a meta-analysis_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

GAO Xudong , HU Yinghan , CHEN Jin , YANG Yujin ,  QUAN Yi

Department of Breast Surgery, Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, P. R. China;

Corresponding?author：

QUAN Yi, Email: quanyi199345@163.com

Keywords：

epidermal growth factor receptor; triple-negative breast cancer; meta-analysis

DOI：

10.7507/1007-9424.202207003

Video：

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Objective To investigate the expression of epidermal growth factor receptor (EGFR) in triple-negative breast cancer (TNBC) and its relation with clinicopathologic features. Methods A computer search of PubMed, Web of Science, CNKI, Wanfang Data, and VIP databases were conducted to select clinical studies on EGFR expression in the TNBC according to the inclusion and exclusion criteria, and the search period was from database establishment to January 2022. Two researchers independently screened the literature, extracted the data, and evaluated the quality of the literature before conducting meta-analysis using RevMan 5.4 software. Results A total of 28 studies including 7 956 patients were included. The results of meta-analysis showed that the positive rate of EGFR expression in the TNBC patients was higher than that in the non-TNBC patients [OR=5.16, 95%CI (4.04, 6.58), P<0.000 01], and the proportions of patients with axillary lymph node metastasis [OR=3.11, 95%CI (1.56, 6.19), P=0.001] and with tumor diameter >2 cm [OR=2.09, 95%CI (1.18, 3.72), P=0.01] in the patients with EGFR positive were higher than those the patients with EGFR negative, no correlation was found that the proportion of patients with histological WHO classification 3 between the patients with EGFR positive expression and EGFR negative expression (P=0.07). Conclusion From the results of this meta-analysis, EGFR expression might be associated with the occurrence, development, and metastasis of patients with TNBC.

Citation： GAO Xudong, HU Yinghan, CHEN Jin, YANG Yujin, QUAN Yi. Expression of epidermal growth factor receptor in triple-negative breast cancer and its correlation with clinicopathologic features：a meta-analysis. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2023, 30(1): 72-79. doi: 10.7507/1007-9424.202207003 Copy

1.	Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin, 2021, 71(3): 209-249.
2.	Brenton JD, Carey LA, Ahmed AA, et al. Molecular classification and molecular forecasting of breast cancer: ready for clinical application? J Clin Oncol, 2005, 23(29): 7350-7360.
3.	Steward L, Conant L, Gao F, et al. Predictive factors and patterns of recurrence in patients with triple negative breast cancer. Ann Surg Oncol, 2014, 21(7): 2165-2171.
4.	中國抗癌協會腫瘤標志專業委員會乳腺癌標志物協作組. 基于靶標指導乳腺癌精準治療標志物臨床應用專家共識(2022版). 中國癌癥防治雜志, 2022, 14(4): 346-362.
5.	You KS, Yi YW, Cho J, et al. Potentiating therapeutic effects of epidermal growth factor receptor inhibition in triple-negative breast cancer. Pharmaceuticals (Basel), 2021, 14(6): 589. doi: 10.3390/ph14060589.
6.	曾憲濤, 劉慧, 陳曦, 等. Meta分析系列之四: 觀察性研究的質量評價工具. 中國循證心血管醫學雜志, 2012, 04(4): 297-299.
7.	Aziz O, Constantinides V, Tekkis PP, et al. Laparoscopic versus open surgery for rectal cancer: a meta-analysis. Ann Surg Oncol, 2006, 13(3): 413-424.
8.	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.
9.	Huang T, Xiang J, Wang Y, et al. Changes of EGFR and SMC4 expressions in triple-negative breast cancer and their early diagnostic value. Gland Surg, 2021, 10(3): 1118-1124.
10.	Kanapathy Pillai SK, Tay A, Nair S, et al. Triple-negative breast cancer is associated with EGFR, CK5/6 and c-KIT expression in Malaysian women. BMC Clin Pathol, 2012, 12: 18. doi: 10.1186/1472-6890-12-18.
11.	Li RH, Huang WH, Wu JD, et al. EGFR expression is associated with cytoplasmic staining of CXCR4 and predicts poor prognosis in triple-negative breast carcinomas. Oncol Lett, 2017, 13(2): 695-703.
12.	Nogi H, Kobayashi T, Suzuki M, et al. EGFR as paradoxical predictor of chemosensitivity and outcome among triple-negative breast cancer. Oncol Rep, 2009, 21(2): 413-417.
13.	Nozoe T, Mori E, Iguchi T, et al. Immunohistochemical expression of epidermal growth factor receptor in breast cancer. Breast Cancer, 2011, 18(1): 37-41.
14.	Rakha EA, El-Sayed ME, Green AR, et al. Prognostic markers in triple-negative breast cancer. Cancer, 2007, 109(1): 25-32.
15.	Rydén L, Jirstr?m K, Haglund M, et al. Epidermal growth factor receptor and vascular endothelial growth factor receptor 2 are specific biomarkers in triple-negative breast cancer. Results from a controlled randomized trial with long-term follow-up. Breast Cancer Res Treat, 2010, 120(2): 491-498.
16.	Tan DS, Marchió C, Jones RL, et al. Triple negative breast cancer: molecular profiling and prognostic impact in adjuvant anthracycline-treated patients. Breast Cancer Res Treat, 2008, 111(1): 27-44.
17.	Tang Y, Zhu L, Li Y, et al. Overexpression of epithelial growth factor receptor (EGFR) predicts better response to neo-adjuvant chemotherapy in patients with triple-negative breast cancer. J Transl Med, 2012, 10 Suppl 1(Suppl 1): S4. doi: 10.1186/1479-5876-10-S1-S4.
18.	萬宇, 黃建軍, 包剛. 三陰性乳腺癌的臨床病理特征和EGFR、Ki67的表達及相關性. 江西醫藥, 2016, 51(4): 291-293, 300.
19.	馮傳寶. EGFR與VEGF在三陰性乳腺癌中的表達及意義. 中國現代醫生, 2017, 55(14): 32-34, 37.
20.	劉莉萍, 孫鳳玲, 魏亞, 等. 表皮生長因子受體、p53、Ki-67在三陰性乳腺癌中的表達及其意義. 腫瘤研究與臨床, 2013, 25(10): 669-671.
21.	吉茹, 李敬永, 趙秀蘭, 等. 三陰性乳腺癌臨床病理特點及與EGFR表達關系的探討. 中國腫瘤臨床, 2010, 37(1): 32-35.
22.	居紅格, 李峰, 馬俊兵, 等. 三陰型乳腺癌中RHBDD1和EGFR的表達及相關性分析. 臨床與實驗病理學雜志, 2020, 36(4): 396-400.
23.	張淼, 任力, 胡蓉, 等. Ki67、EGFR在三陰性及非三陰性乳腺癌中的表達與相關性分析. 武警醫學, 2014, 25(12): 1256-1258.
24.	張言敏, 李紀崗, 郭雪芹, 等. 三陰性乳腺癌的臨床病理特征及CK5/6、E-cad、EGFR的表達的臨床意義. 世界最新醫學信息文摘(連續型電子期刊), 2018, 18(10): 24, 34.
25.	張輝運. CK5/6和EGFR為三陰性乳腺癌預后不良因素的分析. 大連: 大連醫科大學, 2011.
26.	徐英杰, 李巍. 三陰性乳腺癌早期患者雄激素受體、Ki67、p53、表皮生長因子受體表達水平及其與臨床病理特征關系研究. 陜西醫學雜志, 2021, 50(12): 1594-1597.
27.	李華民. EGFR、Ki67在三陰性與非三陰性乳腺癌中的表達及其與TNBC病理特征的相關性. 實用癌癥雜志, 2017, 32(11): 1759-1762.
28.	李曉旭. P53, Ki67, EGFR在三陰性乳腺癌中的表達及臨床意義. 鄭州: 鄭州大學, 2014.
29.	李玥. EGFR和E-cad在三陰性乳腺癌中的表達及臨床意義. 鄭州: 鄭州大學, 2015.
30.	汪鵬剛. 三陰性乳腺癌的臨床病理特征及EGFR與VEGF在三陰性乳腺癌中的表達及意義. 太原: 山西醫科大學, 2016.
31.	王超群, 王艷, 黃必飛, 等. 三陰性和非三陰性乳腺癌中Fascin-1和EGFR表達的相關性研究. 中華內分泌外科雜志, 2018, 12(2): 115-117, 145.
32.	栗艷松. EGFR、Ki-67在三陰性乳腺癌中的表達及相關性臨床研究. 河北醫藥, 2015, 37(13): 1936-1938.
33.	董超, 黃遠麗, 徐正豐. Ki67、EGFR在三陰性乳腺癌中的表達及臨床意義. 世界最新醫學信息文摘, 2017, 17(52): 173-174.
34.	覃咸雄, 孫圣榮. CK5/6、EGFR和E-cadhenrin在三陰性乳腺癌中的表達及意義. 解剖學研究, 2018, 40(3): 169-173.
35.	趙鴻, 薛娣, 冷冬妮. 受體三陰性乳腺癌中CK14和EGFR的檢測及臨床意義. 臨床醫學工程, 2011, 18(6): 862-863.
36.	Mendelsohn J, Baselga J. Status of epidermal growth factor receptor antagonists in the biology and treatment of cancer. J Clin Oncol, 2003, 21(14): 2787-2799.
37.	Kumar R, George B, Campbell MR, et al. HER family in cancer progression: from discovery to 2020 and beyond. Adv Cancer Res, 2020, 147: 109-160.
38.	Tian X, Gu T, Lee MH, et al. Challenge and countermeasures for EGFR targeted therapy in non-small cell lung cancer. Biochim Biophys Acta Rev Cancer, 2022, 1877(1): 188645. doi: 10.1016/j.bbcan.2021.188645.
39.	王璐, 林清, 陸春花, 等. EGFR在三陰性乳腺癌中的表達及放療后表達變化的意義. 醫學研究雜志, 2017, 46(3): 120-123.
40.	馬靜, 任光輝, 馬斌林. 三陰性乳腺癌中EGFR、CK5/6的表達及臨床意義. 新疆醫學, 2015, 45(1): 13-16.
41.	賈占莉, 劉月平. EGFR、CK5/6在三陰性乳腺癌中的表達及其與臨床病理特征關系的探討. 中國抗癌協會腫瘤標志物專業委員會, 河南省抗癌協會. 2018年中國腫瘤標志物學術大會暨第十二屆腫瘤標志物青年科學家論壇. 鄭州: 中國抗癌協會腫瘤標志物專業委員會, 河南省抗癌協會, 2018.
42.	Kyriakopoulou K, Kefali E, Piperigkou Z, et al. Advances in targeting epidermal growth factor receptor signaling pathway in mammary cancer. Cell Signal, 2018, 51: 99-109.
43.	Cox TR. The matrix in cancer. Nat Rev Cancer, 2021, 21(4): 217-238.
44.	Lepedda AJ, Nieddu G, Piperigkou Z, et al. Circulating heparan sulfate proteoglycans as biomarkers in health and disease. Semin Thromb Hemost, 2021, 47(3): 295-307.
45.	Franchi M, Masola V, Bellin G, et al. Collagen fiber array of peritumoral stroma influences epithelial-to-mesenchymal transition and invasive potential of mammary cancer cells. J Clin Med, 2019, 8(2): 213. doi: 10.3390/jcm8020213.
46.	Liang Y, Zhang H, Song X, et al. Metastatic heterogeneity of breast cancer: molecular mechanism and potential therapeutic targets. Semin Cancer Biol, 2020, 60: 14-27.
47.	Micalizzi DS, Ford HL. Epithelial-mesenchymal transition in development and cancer. Future Oncol, 2009, 5(8): 1129-1143.
48.	Dongre A, Weinberg RA. New insights into the mechanisms of epithelial-mesenchymal transition and implications for cancer. Nat Rev Mol Cell Biol, 2019, 20(2): 69-84.
49.	Sznurkowska MK, Aceto N. The gate to metastasis: key players in cancer cell intravasation. FEBS J, 2022, 289(15): 4336-4354.
50.	Rau A, Janssen N, Kühl L, et al. Triple targeting of HER receptors overcomes heregulin-mediated resistance to EGFR blockade in colorectal cancer. Mol Cancer Ther, 2022, 21(5): 799-809.
51.	Lim SO, Li CW, Xia W, et al. EGFR signaling enhances aerobic glycolysis in triple-negative breast cancer cells to promote tumor growth and immune escape. Cancer Res, 2016, 76(5): 1284-1296.
52.	李星枝, 王艦梅, 肖秀麗, 等. GATA-3和EGFR在乳腺癌中表達的相關性及其與分子亞型、臨床病理資料的關系. 川北醫學院學報, 2021, 36(4): 414-418.

1. Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin, 2021, 71(3): 209-249.
2. Brenton JD, Carey LA, Ahmed AA, et al. Molecular classification and molecular forecasting of breast cancer: ready for clinical application? J Clin Oncol, 2005, 23(29): 7350-7360.
3. Steward L, Conant L, Gao F, et al. Predictive factors and patterns of recurrence in patients with triple negative breast cancer. Ann Surg Oncol, 2014, 21(7): 2165-2171.
4. 中國抗癌協會腫瘤標志專業委員會乳腺癌標志物協作組. 基于靶標指導乳腺癌精準治療標志物臨床應用專家共識(2022版). 中國癌癥防治雜志, 2022, 14(4): 346-362.
5. You KS, Yi YW, Cho J, et al. Potentiating therapeutic effects of epidermal growth factor receptor inhibition in triple-negative breast cancer. Pharmaceuticals (Basel), 2021, 14(6): 589. doi: 10.3390/ph14060589.
6. 曾憲濤, 劉慧, 陳曦, 等. Meta分析系列之四: 觀察性研究的質量評價工具. 中國循證心血管醫學雜志, 2012, 04(4): 297-299.
7. Aziz O, Constantinides V, Tekkis PP, et al. Laparoscopic versus open surgery for rectal cancer: a meta-analysis. Ann Surg Oncol, 2006, 13(3): 413-424.
8. 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.
9. Huang T, Xiang J, Wang Y, et al. Changes of EGFR and SMC4 expressions in triple-negative breast cancer and their early diagnostic value. Gland Surg, 2021, 10(3): 1118-1124.
10. Kanapathy Pillai SK, Tay A, Nair S, et al. Triple-negative breast cancer is associated with EGFR, CK5/6 and c-KIT expression in Malaysian women. BMC Clin Pathol, 2012, 12: 18. doi: 10.1186/1472-6890-12-18.
11. Li RH, Huang WH, Wu JD, et al. EGFR expression is associated with cytoplasmic staining of CXCR4 and predicts poor prognosis in triple-negative breast carcinomas. Oncol Lett, 2017, 13(2): 695-703.
12. Nogi H, Kobayashi T, Suzuki M, et al. EGFR as paradoxical predictor of chemosensitivity and outcome among triple-negative breast cancer. Oncol Rep, 2009, 21(2): 413-417.
13. Nozoe T, Mori E, Iguchi T, et al. Immunohistochemical expression of epidermal growth factor receptor in breast cancer. Breast Cancer, 2011, 18(1): 37-41.
14. Rakha EA, El-Sayed ME, Green AR, et al. Prognostic markers in triple-negative breast cancer. Cancer, 2007, 109(1): 25-32.
15. Rydén L, Jirstr?m K, Haglund M, et al. Epidermal growth factor receptor and vascular endothelial growth factor receptor 2 are specific biomarkers in triple-negative breast cancer. Results from a controlled randomized trial with long-term follow-up. Breast Cancer Res Treat, 2010, 120(2): 491-498.
16. Tan DS, Marchió C, Jones RL, et al. Triple negative breast cancer: molecular profiling and prognostic impact in adjuvant anthracycline-treated patients. Breast Cancer Res Treat, 2008, 111(1): 27-44.
17. Tang Y, Zhu L, Li Y, et al. Overexpression of epithelial growth factor receptor (EGFR) predicts better response to neo-adjuvant chemotherapy in patients with triple-negative breast cancer. J Transl Med, 2012, 10 Suppl 1(Suppl 1): S4. doi: 10.1186/1479-5876-10-S1-S4.
18. 萬宇, 黃建軍, 包剛. 三陰性乳腺癌的臨床病理特征和EGFR、Ki67的表達及相關性. 江西醫藥, 2016, 51(4): 291-293, 300.
19. 馮傳寶. EGFR與VEGF在三陰性乳腺癌中的表達及意義. 中國現代醫生, 2017, 55(14): 32-34, 37.
20. 劉莉萍, 孫鳳玲, 魏亞, 等. 表皮生長因子受體、p53、Ki-67在三陰性乳腺癌中的表達及其意義. 腫瘤研究與臨床, 2013, 25(10): 669-671.
21. 吉茹, 李敬永, 趙秀蘭, 等. 三陰性乳腺癌臨床病理特點及與EGFR表達關系的探討. 中國腫瘤臨床, 2010, 37(1): 32-35.
22. 居紅格, 李峰, 馬俊兵, 等. 三陰型乳腺癌中RHBDD1和EGFR的表達及相關性分析. 臨床與實驗病理學雜志, 2020, 36(4): 396-400.
23. 張淼, 任力, 胡蓉, 等. Ki67、EGFR在三陰性及非三陰性乳腺癌中的表達與相關性分析. 武警醫學, 2014, 25(12): 1256-1258.
24. 張言敏, 李紀崗, 郭雪芹, 等. 三陰性乳腺癌的臨床病理特征及CK5/6、E-cad、EGFR的表達的臨床意義. 世界最新醫學信息文摘(連續型電子期刊), 2018, 18(10): 24, 34.
25. 張輝運. CK5/6和EGFR為三陰性乳腺癌預后不良因素的分析. 大連: 大連醫科大學, 2011.
26. 徐英杰, 李巍. 三陰性乳腺癌早期患者雄激素受體、Ki67、p53、表皮生長因子受體表達水平及其與臨床病理特征關系研究. 陜西醫學雜志, 2021, 50(12): 1594-1597.
27. 李華民. EGFR、Ki67在三陰性與非三陰性乳腺癌中的表達及其與TNBC病理特征的相關性. 實用癌癥雜志, 2017, 32(11): 1759-1762.
28. 李曉旭. P53, Ki67, EGFR在三陰性乳腺癌中的表達及臨床意義. 鄭州: 鄭州大學, 2014.
29. 李玥. EGFR和E-cad在三陰性乳腺癌中的表達及臨床意義. 鄭州: 鄭州大學, 2015.
30. 汪鵬剛. 三陰性乳腺癌的臨床病理特征及EGFR與VEGF在三陰性乳腺癌中的表達及意義. 太原: 山西醫科大學, 2016.
31. 王超群, 王艷, 黃必飛, 等. 三陰性和非三陰性乳腺癌中Fascin-1和EGFR表達的相關性研究. 中華內分泌外科雜志, 2018, 12(2): 115-117, 145.
32. 栗艷松. EGFR、Ki-67在三陰性乳腺癌中的表達及相關性臨床研究. 河北醫藥, 2015, 37(13): 1936-1938.
33. 董超, 黃遠麗, 徐正豐. Ki67、EGFR在三陰性乳腺癌中的表達及臨床意義. 世界最新醫學信息文摘, 2017, 17(52): 173-174.
34. 覃咸雄, 孫圣榮. CK5/6、EGFR和E-cadhenrin在三陰性乳腺癌中的表達及意義. 解剖學研究, 2018, 40(3): 169-173.
35. 趙鴻, 薛娣, 冷冬妮. 受體三陰性乳腺癌中CK14和EGFR的檢測及臨床意義. 臨床醫學工程, 2011, 18(6): 862-863.
36. Mendelsohn J, Baselga J. Status of epidermal growth factor receptor antagonists in the biology and treatment of cancer. J Clin Oncol, 2003, 21(14): 2787-2799.
37. Kumar R, George B, Campbell MR, et al. HER family in cancer progression: from discovery to 2020 and beyond. Adv Cancer Res, 2020, 147: 109-160.
38. Tian X, Gu T, Lee MH, et al. Challenge and countermeasures for EGFR targeted therapy in non-small cell lung cancer. Biochim Biophys Acta Rev Cancer, 2022, 1877(1): 188645. doi: 10.1016/j.bbcan.2021.188645.
39. 王璐, 林清, 陸春花, 等. EGFR在三陰性乳腺癌中的表達及放療后表達變化的意義. 醫學研究雜志, 2017, 46(3): 120-123.
40. 馬靜, 任光輝, 馬斌林. 三陰性乳腺癌中EGFR、CK5/6的表達及臨床意義. 新疆醫學, 2015, 45(1): 13-16.
41. 賈占莉, 劉月平. EGFR、CK5/6在三陰性乳腺癌中的表達及其與臨床病理特征關系的探討. 中國抗癌協會腫瘤標志物專業委員會, 河南省抗癌協會. 2018年中國腫瘤標志物學術大會暨第十二屆腫瘤標志物青年科學家論壇. 鄭州: 中國抗癌協會腫瘤標志物專業委員會, 河南省抗癌協會, 2018.
42. Kyriakopoulou K, Kefali E, Piperigkou Z, et al. Advances in targeting epidermal growth factor receptor signaling pathway in mammary cancer. Cell Signal, 2018, 51: 99-109.
43. Cox TR. The matrix in cancer. Nat Rev Cancer, 2021, 21(4): 217-238.
44. Lepedda AJ, Nieddu G, Piperigkou Z, et al. Circulating heparan sulfate proteoglycans as biomarkers in health and disease. Semin Thromb Hemost, 2021, 47(3): 295-307.
45. Franchi M, Masola V, Bellin G, et al. Collagen fiber array of peritumoral stroma influences epithelial-to-mesenchymal transition and invasive potential of mammary cancer cells. J Clin Med, 2019, 8(2): 213. doi: 10.3390/jcm8020213.
46. Liang Y, Zhang H, Song X, et al. Metastatic heterogeneity of breast cancer: molecular mechanism and potential therapeutic targets. Semin Cancer Biol, 2020, 60: 14-27.
47. Micalizzi DS, Ford HL. Epithelial-mesenchymal transition in development and cancer. Future Oncol, 2009, 5(8): 1129-1143.
48. Dongre A, Weinberg RA. New insights into the mechanisms of epithelial-mesenchymal transition and implications for cancer. Nat Rev Mol Cell Biol, 2019, 20(2): 69-84.
49. Sznurkowska MK, Aceto N. The gate to metastasis: key players in cancer cell intravasation. FEBS J, 2022, 289(15): 4336-4354.
50. Rau A, Janssen N, Kühl L, et al. Triple targeting of HER receptors overcomes heregulin-mediated resistance to EGFR blockade in colorectal cancer. Mol Cancer Ther, 2022, 21(5): 799-809.
51. Lim SO, Li CW, Xia W, et al. EGFR signaling enhances aerobic glycolysis in triple-negative breast cancer cells to promote tumor growth and immune escape. Cancer Res, 2016, 76(5): 1284-1296.
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CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Expression of epidermal growth factor receptor in triple-negative breast cancer and its correlation with clinicopathologic features：a meta-analysis

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