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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Abstract Full text Figures/Tables Video References Cited by

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.	中国抗癌协会肿瘤标志专业委员会乳腺癌标志物协作组. 基于靶标指导乳腺癌精准治疗标志物临床应用专家共识(2022版). 中国癌症防治杂志, 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.	曾宪涛, 刘慧, 陈曦, 等. Meta分析系列之四: 观察性研究的质量评价工具. 中国循证心血管医学杂志, 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, Jirström 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.	万宇, 黄建军, 包刚. 三阴性乳腺癌的临床病理特征和EGFR、Ki67的表达及相关性. 江西医药, 2016, 51(4): 291-293, 300.
19.	冯传宝. EGFR与VEGF在三阴性乳腺癌中的表达及意义. 中国现代医生, 2017, 55(14): 32-34, 37.
20.	刘莉萍, 孙凤玲, 魏亚, 等. 表皮生长因子受体、p53、Ki-67在三阴性乳腺癌中的表达及其意义. 肿瘤研究与临床, 2013, 25(10): 669-671.
21.	吉茹, 李敬永, 赵秀兰, 等. 三阴性乳腺癌临床病理特点及与EGFR表达关系的探讨. 中国肿瘤临床, 2010, 37(1): 32-35.
22.	居红格, 李峰, 马俊兵, 等. 三阴型乳腺癌中RHBDD1和EGFR的表达及相关性分析. 临床与实验病理学杂志, 2020, 36(4): 396-400.
23.	张淼, 任力, 胡蓉, 等. Ki67、EGFR在三阴性及非三阴性乳腺癌中的表达与相关性分析. 武警医学, 2014, 25(12): 1256-1258.
24.	张言敏, 李纪岗, 郭雪芹, 等. 三阴性乳腺癌的临床病理特征及CK5/6、E-cad、EGFR的表达的临床意义. 世界最新医学信息文摘(连续型电子期刊), 2018, 18(10): 24, 34.
25.	张辉运. CK5/6和EGFR为三阴性乳腺癌预后不良因素的分析. 大连: 大连医科大学, 2011.
26.	徐英杰, 李巍. 三阴性乳腺癌早期患者雄激素受体、Ki67、p53、表皮生长因子受体表达水平及其与临床病理特征关系研究. 陕西医学杂志, 2021, 50(12): 1594-1597.
27.	李华民. EGFR、Ki67在三阴性与非三阴性乳腺癌中的表达及其与TNBC病理特征的相关性. 实用癌症杂志, 2017, 32(11): 1759-1762.
28.	李晓旭. P53, Ki67, EGFR在三阴性乳腺癌中的表达及临床意义. 郑州: 郑州大学, 2014.
29.	李玥. EGFR和E-cad在三阴性乳腺癌中的表达及临床意义. 郑州: 郑州大学, 2015.
30.	汪鹏刚. 三阴性乳腺癌的临床病理特征及EGFR与VEGF在三阴性乳腺癌中的表达及意义. 太原: 山西医科大学, 2016.
31.	王超群, 王艳, 黄必飞, 等. 三阴性和非三阴性乳腺癌中Fascin-1和EGFR表达的相关性研究. 中华内分泌外科杂志, 2018, 12(2): 115-117, 145.
32.	栗艳松. EGFR、Ki-67在三阴性乳腺癌中的表达及相关性临床研究. 河北医药, 2015, 37(13): 1936-1938.
33.	董超, 黄远丽, 徐正丰. Ki67、EGFR在三阴性乳腺癌中的表达及临床意义. 世界最新医学信息文摘, 2017, 17(52): 173-174.
34.	覃咸雄, 孙圣荣. CK5/6、EGFR和E-cadhenrin在三阴性乳腺癌中的表达及意义. 解剖学研究, 2018, 40(3): 169-173.
35.	赵鸿, 薛娣, 冷冬妮. 受体三阴性乳腺癌中CK14和EGFR的检测及临床意义. 临床医学工程, 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, 陆春花, 等. EGFR在三阴性乳腺癌中的表达及放疗后表达变化的意义. 医学研究杂志, 2017, 46(3): 120-123.
40.	马静, 任光辉, 马斌林. 三阴性乳腺癌中EGFR、CK5/6的表达及临床意义. 新疆医学, 2015, 45(1): 13-16.
41.	贾占莉, 刘月平. EGFR、CK5/6在三阴性乳腺癌中的表达及其与临床病理特征关系的探讨. 中国抗癌协会肿瘤标志物专业委员会, 河南省抗癌协会. 2018年中国肿瘤标志物学术大会暨第十二届肿瘤标志物青年科学家论坛. 郑州: 中国抗癌协会肿瘤标志物专业委员会, 河南省抗癌协会, 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, 王舰梅, 肖秀丽, 等. GATA-3和EGFR在乳腺癌中表达的相关性及其与分子亚型、临床病理资料的关系. 川北医学院学报, 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. 中国抗癌协会肿瘤标志专业委员会乳腺癌标志物协作组. 基于靶标指导乳腺癌精准治疗标志物临床应用专家共识(2022版). 中国癌症防治杂志, 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. 曾宪涛, 刘慧, 陈曦, 等. Meta分析系列之四: 观察性研究的质量评价工具. 中国循证心血管医学杂志, 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, Jirström 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. 万宇, 黄建军, 包刚. 三阴性乳腺癌的临床病理特征和EGFR、Ki67的表达及相关性. 江西医药, 2016, 51(4): 291-293, 300.
19. 冯传宝. EGFR与VEGF在三阴性乳腺癌中的表达及意义. 中国现代医生, 2017, 55(14): 32-34, 37.
20. 刘莉萍, 孙凤玲, 魏亚, 等. 表皮生长因子受体、p53、Ki-67在三阴性乳腺癌中的表达及其意义. 肿瘤研究与临床, 2013, 25(10): 669-671.
21. 吉茹, 李敬永, 赵秀兰, 等. 三阴性乳腺癌临床病理特点及与EGFR表达关系的探讨. 中国肿瘤临床, 2010, 37(1): 32-35.
22. 居红格, 李峰, 马俊兵, 等. 三阴型乳腺癌中RHBDD1和EGFR的表达及相关性分析. 临床与实验病理学杂志, 2020, 36(4): 396-400.
23. 张淼, 任力, 胡蓉, 等. Ki67、EGFR在三阴性及非三阴性乳腺癌中的表达与相关性分析. 武警医学, 2014, 25(12): 1256-1258.
24. 张言敏, 李纪岗, 郭雪芹, 等. 三阴性乳腺癌的临床病理特征及CK5/6、E-cad、EGFR的表达的临床意义. 世界最新医学信息文摘(连续型电子期刊), 2018, 18(10): 24, 34.
25. 张辉运. CK5/6和EGFR为三阴性乳腺癌预后不良因素的分析. 大连: 大连医科大学, 2011.
26. 徐英杰, 李巍. 三阴性乳腺癌早期患者雄激素受体、Ki67、p53、表皮生长因子受体表达水平及其与临床病理特征关系研究. 陕西医学杂志, 2021, 50(12): 1594-1597.
27. 李华民. EGFR、Ki67在三阴性与非三阴性乳腺癌中的表达及其与TNBC病理特征的相关性. 实用癌症杂志, 2017, 32(11): 1759-1762.
28. 李晓旭. P53, Ki67, EGFR在三阴性乳腺癌中的表达及临床意义. 郑州: 郑州大学, 2014.
29. 李玥. EGFR和E-cad在三阴性乳腺癌中的表达及临床意义. 郑州: 郑州大学, 2015.
30. 汪鹏刚. 三阴性乳腺癌的临床病理特征及EGFR与VEGF在三阴性乳腺癌中的表达及意义. 太原: 山西医科大学, 2016.
31. 王超群, 王艳, 黄必飞, 等. 三阴性和非三阴性乳腺癌中Fascin-1和EGFR表达的相关性研究. 中华内分泌外科杂志, 2018, 12(2): 115-117, 145.
32. 栗艳松. EGFR、Ki-67在三阴性乳腺癌中的表达及相关性临床研究. 河北医药, 2015, 37(13): 1936-1938.
33. 董超, 黄远丽, 徐正丰. Ki67、EGFR在三阴性乳腺癌中的表达及临床意义. 世界最新医学信息文摘, 2017, 17(52): 173-174.
34. 覃咸雄, 孙圣荣. CK5/6、EGFR和E-cadhenrin在三阴性乳腺癌中的表达及意义. 解剖学研究, 2018, 40(3): 169-173.
35. 赵鸿, 薛娣, 冷冬妮. 受体三阴性乳腺癌中CK14和EGFR的检测及临床意义. 临床医学工程, 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, 陆春花, 等. EGFR在三阴性乳腺癌中的表达及放疗后表达变化的意义. 医学研究杂志, 2017, 46(3): 120-123.
40. 马静, 任光辉, 马斌林. 三阴性乳腺癌中EGFR、CK5/6的表达及临床意义. 新疆医学, 2015, 45(1): 13-16.
41. 贾占莉, 刘月平. EGFR、CK5/6在三阴性乳腺癌中的表达及其与临床病理特征关系的探讨. 中国抗癌协会肿瘤标志物专业委员会, 河南省抗癌协会. 2018年中国肿瘤标志物学术大会暨第十二届肿瘤标志物青年科学家论坛. 郑州: 中国抗癌协会肿瘤标志物专业委员会, 河南省抗癌协会, 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, 王舰梅, 肖秀丽, 等. GATA-3和EGFR在乳腺癌中表达的相关性及其与分子亚型、临床病理资料的关系. 川北医学院学报, 2021, 36(4): 414-418.

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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