Preview

Bulletin of Siberian Medicine

Advanced search

The role of epidermal growth factor receptor (EGFR) in the efficacy of neoadjuvant chemotherapy in triple-negative breast cancer patients

https://doi.org/10.20538/1682-0363-2020-1-13-20

Abstract

Background. Identification of predictive molecular markers of triple-negative breast cancer (TNBC) will enable the evaluation of the efficacy of neoadjuvant chemotherapy (NACT) and define optimum approaches for the prognosis of the disease course in TNBC patients.

The aim of the study was to examine the correlation between the expression of the epidermal growth factor receptor (EGFR), its gene’s polymorphic variants and the neoadjuvant chemotherapy (NACT) efficacy in triple-negative breast cancer (TNBC) patients.

Materials and methods. The study included 70 patients with triple-negative breast cancer, who had received 2-4 cycles of FAC and CAX regimens. The efficacy of the neoadjuvant chemotherapy was assessed according to the RECIST scale. The EGFR expression level in tumors before and after the NACT was evaluated with the help of immunohistochemistry. Genotypes for EGFR (rs2227983 and rs1468727) were detected by a real-time PCR.

Results. It was found that NCT significantly decreases the EGFR expression level in the tumor (p = 0.000). The research associates the objective clinical response as well as the pathological complete response with the low EGFR expression level (p = 0.007 and p = 0.000 respectively). Patients carrying the EGFRCC mutant genotype of rs1468727 did not achieve a pathological complete response (p = 0.042). In addition, patients with EGFRCC mutant genotype are more likely to have tumors with a high EGFR expression compared to EGFRTT wild-type genotype patients (p = 0.047).

Conclusion. The EGFR expression level in tumor tissue and the polymorphic variants of its gene in the rs1468727 locus can be considered as potential molecular markers with predictive significance in relation to the NACT efficacy in triple-negative breast cancer patients.

About the Authors

N. N. Babyshkina
Cancer Research Institute, Tomsk National Research Medical Center (NRMC) of Russian Academy of Sciences; National Research Tomsk State University (NR TSU)
Russian Federation

5, Kooperativny Str., Tomsk, 634050, Russian Federation

36, Lenin Av., Tomsk, 634050, Russian Federation



T. A. Dronova
Cancer Research Institute, Tomsk National Research Medical Center (NRMC) of Russian Academy of Sciences; National Research Tomsk State University (NR TSU)
Russian Federation

5, Kooperativny Str., Tomsk, 634050, Russian Federation

36, Lenin Av., Tomsk, 634050, Russian Federation



E. A. Zambalova
Cancer Research Institute, Tomsk National Research Medical Center (NRMC) of Russian Academy of Sciences
Russian Federation

5, Kooperativny Str., Tomsk, 634050, Russian Federation

 



M. V. Zavyalova
Cancer Research Institute, Tomsk National Research Medical Center (NRMC) of Russian Academy of Sciences; National Research Tomsk State University (NR TSU); Siberian State Medical University (SSMU)
Russian Federation

5, Kooperativny Str., Tomsk, 634050, Russian Federation

36, Lenin Av., Tomsk, 634050, Russian Federation

2, Moscow Trakt, Tomsk, 634050, Russian Federation



E. M. Slonimskaya
Cancer Research Institute, Tomsk National Research Medical Center (NRMC) of Russian Academy of Sciences; Siberian State Medical University (SSMU)
Russian Federation

5, Kooperativny Str., Tomsk, 634050, Russian Federation

2, Moscow Trakt, Tomsk, 634050, Russian Federation



N. V. Cherdyntseva
Cancer Research Institute, Tomsk National Research Medical Center (NRMC) of Russian Academy of Sciences; National Research Tomsk State University (NR TSU)
Russian Federation

5, Kooperativny Str., Tomsk, 634050, Russian Federation

36, Lenin Av., Tomsk, 634050, Russian Federation



References

1. De Ruijter T.C., Veeck J., de Hoon J.P., van Engeland M., Tjan-Heijnen V.C. Characteristics of triple-negative breast cancer. Clin. Oncol. 2011; 137 (2): 183–192. DOI: 10.1007/s00432-010-0957-x.

2. Wahba H.A., El-Hadaad H.A. Current approaches in treatment of triple-negative breast cancer. Cancer Biol. Med. 2015; 12 (2): 106–116. DOI: 10.7497/j.issn.2095-3941.2015.0030.

3. Oualla K., El-Zawahry H.M., Arun B., Reuben J.M., Woodward W.A., Gamal El-Din H., Lim B., Mellas N., Ueno N.T., Fouad T.M. Novel therapeutic strategies in the treatment of triple-negative breast cancer. Ther. Adv. Med. Oncol. 2017; 9 (7): 493–511. DOI: 10.1177/1758834017711380.

4. Voduc K.D., Cheang M.C., Tyldesley S., Gelmon K., Nielsen T.O., Kennecke H. Breast cancer subtypes and the risk of local and regional relapse. Journal of Clinical Oncology. 2010; 28 (10): 1684–1691. DOI: 10.1200/JCO.2009.24.9284.

5. Cortazar P., Zhang L., Untch M., Mehta K., Costantino J.P., Wolmark N., Bonnefoi H., Cameron D., Gianni L., Valagussa P., Swain S.M., Prowell T., Loibl S., Wickerham D.L., Bogaerts J., Baselga J., Perou C., Blumenthal G., Blohmer J., Mamounas E.P., Bergh J., Semiglazov V., Justice R., Eidtmann H., Paik S., Piccart M., Sridhara R., Fasching P.A., Slaets L., Tang S., Gerber B., Geyer C.E. Jr., Pazdur R., Ditsch N., Rastogi P., Eiermann W., von Minckwitz G. Pathological complete response and long-term clinical benefit in breast cancer: the CTNeoBC pooled analysis. Lancet. 2014; 384 (9938): 164–172. DOI: 10.1016/S0140-6736(13)62422-8.

6. Osborne C.K., Schiff R. Mechanisms of endocrine resistance in breast cancer. Ann. Rev. Med. 2011; 62: 233–247. DOI: 10.1146/annurev-med-070909-182917.

7. Chong K., Subramanian A., Sharma A., Mokbel K. Measuring IGF-1, ER-α and EGFR expression can predict tamoxifen-resistance in ER-positive breast cancer. Anticancer Res. 2011; 31 (1):23–32.

8. Дронова Т.А., Бабышкина Н.Н., Завьялова М.В., Паталяк С.В., Слонимская Е.М., Чердынцева Н.В., Кжышковска Ю.Г. Взаимосвязь компонентов EGFR/PI3K/AKT-сигнального пути с эффективностью терапии тамоксифеном у больных эстрогензависимым раком молочной железы. Успехи молекулярной онкологии. 2018; 5 (3): 40–50. DOI: 10.17650/2313-805X-2018-5-3-40-50.

9. Tischkowitz M., Brunet J.S., Begin L.R., Huntsman D.G., Cheang M.C., Akslen L.A., Nielsen T.O., Foulkes W.D. Use of immunohistochemical markers can refine prognosis in triple negative breast cancer. BMC Cancer. 2007; 7: 134. DOI: 10.1186/1471-2407-7-134.

10. Park H.S., Jang M.H., Kim E.J., Kim H.J., Lee H.J., Kim Y.J., Kim J.H., Kang E., Kim S.W., Kim I.A., Park S.Y. High EGFR gene copy number predicts poor outcome in triple-negative breast cancer. Mod. Pathol. 2014; 27 (9): 1212–1222. DOI: 10.1038/modpathol.2013.251.

11. Zhang M., Zhang X., Zhao S., Wang Y., Di W., Zhao G., Yang M., Zhang Q. Prognostic value of survivin and EGFR protein expression in triple-negative breast cancer (TNBC) patients. Target Oncol. 2014; 9 (4): 349–357. DOI: 10.1007/s11523-013-0300-y.

12. Yue Y., Astvatsaturyan K., Cui X., Zhang X., Fraass B., Bose S. Stratification of prognosis of triple-negative breast cancer patients using combinatorial biomarkers. PLoS One. 2016; 11 (3): e0149661. DOI: 10.1371/journal.pone.0149661.

13. Abdelrahman A.E., Rashed H.E., Abdelgawad M., Abdelhamid M. Prognostic impact of EGFR and cytokeratin 5/6 immunohistochemical expression in triple-negative breast cancer. Ann. Diagn. Pathol. 2017; 28: 43–53. DOI: 10.1016/j.anndiagpath.2017.01.009.

14. Foidart P., Yip C., Radermacher J., Blacher S., Lienard M., Montero-Ruiz L., Maquoi E., Montaudon E., Château-Joubert S., Collignon J., Coibion M., Jossa V., Marangoni E., Noël A., Sounni N.E., Jerusalem G. Expression of MT4-MMP, EGFR, and RB in triple-negative breast cancer strongly sensitizes tumors to erlotinib and palbociclib combination therapy. Clin. Cancer Res. 2019; 25 (6): 1838–1850. DOI: 10.1158/1078-0432.CCR-18-1880.

15. Лушников Е.Ф. Лучевой патоморфоз опухолей человека. M.: Медицина, 1977: 327.

16. Van Reesema L.L.S., Zheleva V., Winston J.S., Jansen R.J., O’Connor C.F., Isbell A.J., Bian M., Qin R., Bassett P.T., Hinson V.J., Dorsch K.A., Kirby B.W., van Sciver R.E., Tang-Tan A.M., Harden E.A., Chang D.Z., Allen C.A., Perry R.R., Hoefer R.A., Tang A.H. SIAH and EGFR, two RAS pathway biomarkers, are highly prognostic in locally advanced and metastatic breast cancer. EBioMedicine. 2016; 11: 183–198. DOI: 10.1016/j.ebiom.2016.08.014.

17. Tang Y., Zhu L., Li Y., Ji J., Li J., Yuan F., Wang D., Chen W., Huang O., Chen X., Wu J., Shen K., Loo W.T., Chow L.W. 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 (1): S4. DOI: 10.1186/1479-5876-10-S1-S4.

18. Li B., Zhao W., Li J., Yan M., Xie Z., Zhu Y., Chen C., Jin T. Effect of epidermal growth factor receptor gene polymorphisms on prognosis inglioma patients. Oncotarget. 2016; 7(39): 63054–63064. DOI: 10.18632/oncotarget.10666.

19. Wang X., Zhang H., Wang D., Li X. Association of genetic polymorphisms of EGFR with glioma in a Chinese population. Genet. Test Mol. Biomarkers. 2015; 19 (1): 59–62. DOI:10.1089/gtmb.2014.0228.


Review

For citations:


Babyshkina N.N., Dronova T.A., Zambalova E.A., Zavyalova M.V., Slonimskaya E.M., Cherdyntseva N.V. The role of epidermal growth factor receptor (EGFR) in the efficacy of neoadjuvant chemotherapy in triple-negative breast cancer patients. Bulletin of Siberian Medicine. 2020;19(1):13-20. https://doi.org/10.20538/1682-0363-2020-1-13-20

Views: 1143


Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.


ISSN 1682-0363 (Print)
ISSN 1819-3684 (Online)