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Effect of neoadjuvant chemotherapy on ER, PR, c-erb2, VEGF and Ki-67 in patients with locally advanced breast cancer

Year 2019, Volume: 44 Issue: 1, 226 - 231, 31.03.2019
https://doi.org/10.17826/cumj.412192

Abstract

Purpose: The aim of this study is aimed to demonstrate the changes in the tumor diameter and expressions of vascular endothelial growth factor (VEGF), estrogen receptor (ER), progesterone receptor (PR), Ki-67, and Cerb-B2 status after neoadjuvant chemotherapy in the patients with locally advanced breast cancer.

Materials and Methods: Sixty-nine patients who diagnosed with locally advanced breast cancer and treated with were prospectively evaluated.  The tumor diameter and VEGF, Ki-67, ER, PR, and Cerb-B2 expressions tested by immunohistochemistry (IHC) were evaluated before and after neoadjuvant chemotherapy.

Results: There was a statistically significant reduction in the tumor diameter and in the expression of VEGF, Ki-67, ER, PR, and Cerb-B2 after neoadjuvant chemotherapy. 

Conclusion: The significant reduction in VEGF expression suggests that the tumor angiogenesis and its metastatic ability may be reduced by neoadjuvant chemotherapy. The significant change in the Ki-67 proliferation index may suggest the reduced proliferative activity of malignant cells with neoadjuvant chemotherapy.


References

  • 1. Jatoi I. Breast cancer: a systemic or local disease? Am J ClinOncol 1997; 20(5):536-9.
  • 2. Güler N, Karabulut B, Koçdor MA, Kaya H, Esen G, Özaslan C, Saip P, Görken İ. Locally Advanced Breast Cancer-2010 Istanbul breast cancer Consensus Meeting. The Journal of Breast Health 2011:7(2);68-85.
  • 3. Edge SB, Byrd DR, Compton CC, Fritz AG, Grene FI, Trotti A (Eds). Breast in AJCC Cancer Staging Manual. Seventh Edition. Springer, Chicago, IL 2010:345-377
  • 4. Kim EA, Gershtein ES, Vyotskaya IV, Kushlinskii NE. Expression of VEGF and VEGFR2 in tumors during neoadjuvant therapy of patients with breast cancer. Bull Exp Biol Med. 2008;145(2):245-8.
  • 5. Burcombe RJ, Makris A, Richman PI, Daley FM, Noble S, Pittam M, Wright D, Allen SA, Dove J, Wilson D. Evaluation of ER, PgR, HER-2 and Ki-67 as predictors of response to neoadjuvant anthracycline chemotherapy for operable breast cancer. Br J Cancer 2005;92(1):147-55.
  • 6. Arens N, Bleyl U, Hildenbrand R. HER2/neu, p53, Ki67, and hormone receptors do not change during neoadjuvant chemotherapy in breast cancer. Virchows Arch 2005;446(5):489-96
  • 7. Matsubara N, Mukai H, Fujii S, Wada N. Different prognostic significance of Ki-67 change between pre- and post-neoadjuvant chemotherapy in various subtypes of breast cancer . Brest Can Res Treat 2013;137(1):203-12.
  • 8. Dede DS, Gumuskaya B, Guler G, Onat D, Altundag K, Ozisik Y. Evaluation of changes of biologic markers ER, PR, HER 2 and Ki-67 in breast cancer with administration of neoadjuvant dose-dense doxorubicin, cyclophosphamide followed by paclitaxel. JBUON 2013;18(2):366-71
  • 9. Colleoni M, Giuseppe V, David Z. Chemotherapy Is More Effective in Patients with Breast Cancer Not Expressing Steroid Hormone Receptors: A Study of Preoperative Treatment. Clin Cancer Research 2004:10;6622-6628
  • 10. Faneyte IF, Schrama JG, Peterse JL, Remijnse PL, Rodenhuis S, van de Vijver MJ. Breast cancer response to neoadjuvant chemotherapy: predictive markers and relation with outcome. Br J Cancer 2003:10;88(3):406-12
  • 11. Miglietta L, Vanella P, Canobbio L, Naso C, Cerisola N, Meszaros P, Parodi MA, Morabito F. Prognostic Value of Estrogen Receptor and Ki-67 Index after Neoadjuvant chemotherapy in locally advanced breast cancer expressing high levels of proliferation at diagnosis. Oncology 2010;79:255–261.
  • 12. Kinsella MD, Nassar A, Siddiqui1 MT, Cohen C. Estrogen receptor (ER), progesterone receptor (PR), and HER2 expression pre- and post- neoadjuvant chemotherapy in primary breast carcinoma: a single institutional experience. Int J Clin Exp Pathol. 2012;5(6):530-6
  • 13. Adams AL, Eltoum I, Krontiras H, Wang W, Chhieng DC. The effect of neoadjuvant chemotherapy on histologic grade, hormone receptor status, and HER2/neu status in breast carcinoma. Breast J 2008;14(2):141-146
  • 14. Penault-Llorca F, Cayre A, BouchetMishellany F, Amat S, Feillel V, Le Bouedec G, Ferrière JP, De Latour M, Chollet P. Induction chemotherapy for breast carcinoma: predictive markers and relation with outcome, Int J Oncol. 2003;22(6):1319-25.
  • 15. Schneider J, Lucas R, Sánchez J, Ruibal A, Tejerina A, Martín M. Modulation of molecular marker expression by induction chemotherapy in locally advanced breast cancer: correlation with the response to therapy and the expression of MDR1 and LRP. Anticancer Res. 2000; 20(6B):4373-7.
  • 16. Varga Z, Caduff R, Pestalozzi B. Stability of the HER2 gene after primary chemotherapy in advanced breast, Virchows Arch. 2005;446(2):136-41
  • 17.KayaAO, Büyükberber S, Yamaç D. Changes in Hormone Receptor and Her2 Status After Neoadjuvant Chemotherapy in Breast Cancer J Med Sci 2010;30(2):469
  • 18. Makris A, Powles TJ, Dowsett M, Osborne CK, Trott PA, Fernando IN, Ashley SE, Ormerod MG, Titley JC, Gregory RK, Allred DC. Prediction of response to neoadjuvantchemoendocrine therapy in primary breast carcinomas. Clin Cancer Res 1997; 3:593-600.
  • 19. Neubauer H, Gall C, Vogel U, Hornung R, Wallwiener D, Solomayer E, Fehm T. Changes in Tumour Biological Markers duringPrimary Systemic Chemotherapy (PST) Anticancer research 2008;28:1797-1804
  • 20. Partridge SC, Gibbs JE, Lu Y, Esserman LJ, Tripathy D, Wolverton DS, Rugo HS, Hwang ES, Ewing CA, Hylton NM. MRI Measurements of Breast Tumor Volume Predict Response to Neoadjuvant Chemotherapy and Recurrence-Free Survival.AJR Am J Roentgenol. 2005184(6); 184:6
  • 21. Kuehn T, Bauerfeind I, Fehm T, Fleige B, Hausschild M, Helms G, Lebeau A, Liedtke C, von Minckwitz G, Nekljudova V, Schmatloch S, Schrenk P, Staebler A,Untch M. Sentinel-lymph-node biopsy in patients with breast cancer before and after neoadjuvant chemotherapy (SENTINA): a prospective, multicentre cohort study. Lancet Oncol. 2013;14(7):609-18.
  • 22. Sun B, Song ST, Jiang ZF, Wang T, Zhang SH, Meng XY, Li XB, Yu CZ, Wu SK. Analysis of the factors affecting pathologic complete response to neoadjuvant chemotherapy in breast cancer patients. Zhonghua Zhong Liu Za Zhi. 2013;35(1):38-42.

Lokal ileri evre meme kanserli hastalarda neoadjuvan kemoterapinin ER, PR, c-erb2, VEGF ve Ki-67 üzerine etkisi

Year 2019, Volume: 44 Issue: 1, 226 - 231, 31.03.2019
https://doi.org/10.17826/cumj.412192

Abstract

Amaç: Bu çalışmada lokal ileri evre meme kanserli hastalarda neoadjuvan kemoterapi ile tümör çapı, tümörlü dokuda çalışılan vasküler endotelyal büyüme faktörü (VEGF), östrojen reseptörü (ER), progesteron reseptörü (PR), Ki-67 ve Cerb-B2 ekspresyonlarındaki değişimin gösterilmesi amaçlanmıştır.

Gereç ve Yöntem: Çukurova Üniversitesi Tıp Fakültesi Genel Cerrahi ve Tıbbi Onkoloji Bilim Dalı’nda 2008 ve 2013 yılları arasında lokal ileri meme kanseri nedeniyle tedavi gören 69 hastanın verileri prospektif olarak araştırılmıştır. Tümör çapı, tümörlü dokuda çalışılan VEGF, Ki-67, ER, PR ve Cerb-B2 ekspresyonları immunhistokimyasal (İHK) yöntem ile neoadjuvan kemoterapi öncesi ve sonrası dönemde karşılaştırmalı olarak değerlendirilmiştir.

Bulgular: Neoadjuvan kemoterapi sonrası tümör çapı, VEGF, Ki-67, ER, PR ve Cerb-B2 ekspresyonlarında istatistiksel olarak anlamlı düşüş saptandı. 

Sonuç: Tümör dokusunda çalışılan VEGF düzeyindeki anlamlı düşme, tümörün anjiyogenezinin ve bu yolla metastaz yapabilme yeteneğinin neoadjuvan kemoterapi etkisiyle azalabileceği sonucunu telkin etmektedir. Tümör dokusunda çalışılan Ki-67 proliferasyon indeksinde  anlamlı değişim; malign hücre proliferasyonunun neoadjuvan kemoterapi etkisiyle azaldığını gösterebilir.


References

  • 1. Jatoi I. Breast cancer: a systemic or local disease? Am J ClinOncol 1997; 20(5):536-9.
  • 2. Güler N, Karabulut B, Koçdor MA, Kaya H, Esen G, Özaslan C, Saip P, Görken İ. Locally Advanced Breast Cancer-2010 Istanbul breast cancer Consensus Meeting. The Journal of Breast Health 2011:7(2);68-85.
  • 3. Edge SB, Byrd DR, Compton CC, Fritz AG, Grene FI, Trotti A (Eds). Breast in AJCC Cancer Staging Manual. Seventh Edition. Springer, Chicago, IL 2010:345-377
  • 4. Kim EA, Gershtein ES, Vyotskaya IV, Kushlinskii NE. Expression of VEGF and VEGFR2 in tumors during neoadjuvant therapy of patients with breast cancer. Bull Exp Biol Med. 2008;145(2):245-8.
  • 5. Burcombe RJ, Makris A, Richman PI, Daley FM, Noble S, Pittam M, Wright D, Allen SA, Dove J, Wilson D. Evaluation of ER, PgR, HER-2 and Ki-67 as predictors of response to neoadjuvant anthracycline chemotherapy for operable breast cancer. Br J Cancer 2005;92(1):147-55.
  • 6. Arens N, Bleyl U, Hildenbrand R. HER2/neu, p53, Ki67, and hormone receptors do not change during neoadjuvant chemotherapy in breast cancer. Virchows Arch 2005;446(5):489-96
  • 7. Matsubara N, Mukai H, Fujii S, Wada N. Different prognostic significance of Ki-67 change between pre- and post-neoadjuvant chemotherapy in various subtypes of breast cancer . Brest Can Res Treat 2013;137(1):203-12.
  • 8. Dede DS, Gumuskaya B, Guler G, Onat D, Altundag K, Ozisik Y. Evaluation of changes of biologic markers ER, PR, HER 2 and Ki-67 in breast cancer with administration of neoadjuvant dose-dense doxorubicin, cyclophosphamide followed by paclitaxel. JBUON 2013;18(2):366-71
  • 9. Colleoni M, Giuseppe V, David Z. Chemotherapy Is More Effective in Patients with Breast Cancer Not Expressing Steroid Hormone Receptors: A Study of Preoperative Treatment. Clin Cancer Research 2004:10;6622-6628
  • 10. Faneyte IF, Schrama JG, Peterse JL, Remijnse PL, Rodenhuis S, van de Vijver MJ. Breast cancer response to neoadjuvant chemotherapy: predictive markers and relation with outcome. Br J Cancer 2003:10;88(3):406-12
  • 11. Miglietta L, Vanella P, Canobbio L, Naso C, Cerisola N, Meszaros P, Parodi MA, Morabito F. Prognostic Value of Estrogen Receptor and Ki-67 Index after Neoadjuvant chemotherapy in locally advanced breast cancer expressing high levels of proliferation at diagnosis. Oncology 2010;79:255–261.
  • 12. Kinsella MD, Nassar A, Siddiqui1 MT, Cohen C. Estrogen receptor (ER), progesterone receptor (PR), and HER2 expression pre- and post- neoadjuvant chemotherapy in primary breast carcinoma: a single institutional experience. Int J Clin Exp Pathol. 2012;5(6):530-6
  • 13. Adams AL, Eltoum I, Krontiras H, Wang W, Chhieng DC. The effect of neoadjuvant chemotherapy on histologic grade, hormone receptor status, and HER2/neu status in breast carcinoma. Breast J 2008;14(2):141-146
  • 14. Penault-Llorca F, Cayre A, BouchetMishellany F, Amat S, Feillel V, Le Bouedec G, Ferrière JP, De Latour M, Chollet P. Induction chemotherapy for breast carcinoma: predictive markers and relation with outcome, Int J Oncol. 2003;22(6):1319-25.
  • 15. Schneider J, Lucas R, Sánchez J, Ruibal A, Tejerina A, Martín M. Modulation of molecular marker expression by induction chemotherapy in locally advanced breast cancer: correlation with the response to therapy and the expression of MDR1 and LRP. Anticancer Res. 2000; 20(6B):4373-7.
  • 16. Varga Z, Caduff R, Pestalozzi B. Stability of the HER2 gene after primary chemotherapy in advanced breast, Virchows Arch. 2005;446(2):136-41
  • 17.KayaAO, Büyükberber S, Yamaç D. Changes in Hormone Receptor and Her2 Status After Neoadjuvant Chemotherapy in Breast Cancer J Med Sci 2010;30(2):469
  • 18. Makris A, Powles TJ, Dowsett M, Osborne CK, Trott PA, Fernando IN, Ashley SE, Ormerod MG, Titley JC, Gregory RK, Allred DC. Prediction of response to neoadjuvantchemoendocrine therapy in primary breast carcinomas. Clin Cancer Res 1997; 3:593-600.
  • 19. Neubauer H, Gall C, Vogel U, Hornung R, Wallwiener D, Solomayer E, Fehm T. Changes in Tumour Biological Markers duringPrimary Systemic Chemotherapy (PST) Anticancer research 2008;28:1797-1804
  • 20. Partridge SC, Gibbs JE, Lu Y, Esserman LJ, Tripathy D, Wolverton DS, Rugo HS, Hwang ES, Ewing CA, Hylton NM. MRI Measurements of Breast Tumor Volume Predict Response to Neoadjuvant Chemotherapy and Recurrence-Free Survival.AJR Am J Roentgenol. 2005184(6); 184:6
  • 21. Kuehn T, Bauerfeind I, Fehm T, Fleige B, Hausschild M, Helms G, Lebeau A, Liedtke C, von Minckwitz G, Nekljudova V, Schmatloch S, Schrenk P, Staebler A,Untch M. Sentinel-lymph-node biopsy in patients with breast cancer before and after neoadjuvant chemotherapy (SENTINA): a prospective, multicentre cohort study. Lancet Oncol. 2013;14(7):609-18.
  • 22. Sun B, Song ST, Jiang ZF, Wang T, Zhang SH, Meng XY, Li XB, Yu CZ, Wu SK. Analysis of the factors affecting pathologic complete response to neoadjuvant chemotherapy in breast cancer patients. Zhonghua Zhong Liu Za Zhi. 2013;35(1):38-42.
There are 22 citations in total.

Details

Primary Language English
Subjects Health Care Administration
Journal Section Research
Authors

Ahmet Gökhan Sarıtaş 0000-0002-2039-3994

Orçun Yalav

Yalçın Kekeç This is me

Gürhan Sakman

Emine Kılıç

Suzan Zorludemir This is me

Melek Ergin This is me

İsmail Cem Eray This is me

Oğuz Kara This is me

Semra Paydaş

Publication Date March 31, 2019
Acceptance Date November 28, 2018
Published in Issue Year 2019 Volume: 44 Issue: 1

Cite

MLA Sarıtaş, Ahmet Gökhan et al. “Effect of Neoadjuvant Chemotherapy on ER, PR, C-erb2, VEGF and Ki-67 in Patients With Locally Advanced Breast Cancer”. Cukurova Medical Journal, vol. 44, no. 1, 2019, pp. 226-31, doi:10.17826/cumj.412192.