Volume 7, Issue 1, March 2019, Page: 8-17
Impact of Neoadjuvant Chemotherapy on Breast Cancer Biomarkers: A Guide for Further Adjuvant Treatment
Ghada Ezzat Eladawei, Clinical Oncology & Nuclear Medicine Department, Mansoura University, Mansoura, Eygpt
Dina Abdallah Elnady, Pathology Department, Mansoura University, Mansoura, Eygpt
Ashraf Khater, Surgical Oncology Department, Oncology Centre, Mansoura University, Mansoura, Eygpt
Sheref Mohamed El-taher, Public Health & Community Medicine Department, Benha University, Benha, Eygpt
Received: Jan. 22, 2019;       Accepted: Feb. 27, 2019;       Published: Mar. 20, 2019
DOI: 10.11648/j.crj.20190701.12      View  42      Downloads  15
Abstract
Introduction and objective: There is discrepancy in practice worldwide whether testing molecular profile on residual carcinoma is warranted and if treatment options should be modified according to final molecular profile of tumor. Therefore, the current study was conducted to evaluate potential changes in breast biomarkers; estrogen receptor, progesterone receptor, HER-2 and Ki67 expression before and after neoadjuvant chemotherapy in Egyptian patients with breast cancer. Patients and method: a hundred locally advanced (initial clinical stage IIB-IIIC) breast carcinoma patients were treated by one of two protocols of neoadjuvant chemotherapy. First protocol: 4 cycles of AC (adriamycin, cyclophosamide) repeated every 21 days, followed by 12 weeks of paclitaxel. Second protocol: FAC (fluorouracil, adriamycin, cyclophosamide) or FEC (fluorouracil, epirubicin, cyclophosamide) for 6 cycles to be repeated every 21 days. Immunohistochemisty of breast biomarkers were performed on both initial biopsies and also surgical resection specimens for each patient. Result: There was statistically significant change of ER (p=0.03). Fifty five tumors were initially negative and thirty nine became negative after neoadjuvant chemotherapy. The rate of conversion from negative to positive was 14%. Forty seven of tumors were initially negative progesterone receptors (PR) and sixty two became negative after neoadjuvant chemotherapy. PR status showed statistically significant change between before and after neoadjuvant chemotherapy (p=0.04). The rate of conversion of PR from positive to negative was 15%. There is no statistically significant change of HER-2 before and after neoadjuvant chemotherapy (p=0.98). There is statistically significant change from high to low Ki 67 index (p=0.006). Rate of conversion changes of Ki 67 from high to low was 20%. Conclusion: neoadjuvant chemotherapy change receptor status and reduce K i67 expression. This change in hormone receptor status from negative to positive offers new endocrine therapy to this group of patients. Accordingly, reevaluation of hormone receptors after neoadjuvant chemotherapy is required to guide further adjuvant treatment.
Keywords
Breast Cancer, Neoadjuvant Chemotherapy, ER, PR, HER2, Ki67
To cite this article
Ghada Ezzat Eladawei, Dina Abdallah Elnady, Ashraf Khater, Sheref Mohamed El-taher, Impact of Neoadjuvant Chemotherapy on Breast Cancer Biomarkers: A Guide for Further Adjuvant Treatment, Cancer Research Journal. Vol. 7, No. 1, 2019, pp. 8-17. doi: 10.11648/j.crj.20190701.12
Copyright
Copyright © 2019 Authors retain the copyright of this article.
This article is an open access article distributed under the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Reference
[1]
Azim HA and Ibrahim A S, Breast cancer in Egypt, China and Chinese: statistics and beyond, J Thorac Dis, 2014 Jul; 6(7):864-866.
[2]
Harris L, Fritsche H, Mennel R, Norton L, Ravdin P, Taube S, et al. American Society of Clinical Oncology 2007 update of recommendations for the use of tumour markers in breast cancer. J Clin Oncol. 2007; 25: 5287–312.
[3]
Thompson AM, Moulder-Thompson SL. Neoadjuvant treatment of breast cancer. Ann Oncol 2012; 23(Suppl. 10): x231e6.
[4]
Kaufmann M, von Minckwitz G, Smith R, Valero V, Gianni L, Eiermann W et al. International expert panel on the use of primary (preoperative) systemic treatment of operable breast cancer: reveiw and recommendations. J Clin Oncol. 2003; 21: 2600–2608.
[5]
Loibl S, von Minckwitz G, Raab G, Blohmer JU, Dan Costa S, Gerber B, et al. Surgical procedures after neoadjuvant chemotherapy in operable breast cancer: results of the GEPARDUO trial. Ann Surg Oncol. 2006; n13: 1434–1442.
[6]
National Institute for Health and Care Excellence. Early and locally advanced breast cancer: diagnosis and treatment, NICE guidelines [CG80]. NICE; 2009.
[7]
Guarneri V, Broglio K, Kau S. W , Cristofanilli M, Buzdar AU, Valero V et al., Prognostic value of pathologic complete response after primary chemotherapy in relation to hormone receptor status and other factors, J. Clin. Oncol. 24(2006)1037–1044.
[8]
Zujewski J., Liu E. T, The 1998 St. Gallen's consensus conference: an assessment, J. Natl. Cancer Inst.90 (1998) 1587–1589.
[9]
Goldhirsch A, Glick J. H, Gelber R. D, Senn H. J, Meeting highlights: international consensus panel on the treatment of primary breast cancer, J. Natl. Cancer Inst.90 (1998)1601–1608.
[10]
Goldhirsch A, Wood W. C, Coates A. S, Gelber, R. D., Thürlimann, B., Senn, H. J., et al. Strategies for subtypes–dealing with the diversity of breast cancer: high lights of the St. Gallen International Expert consensus on the primary therapy of early breast cancer, Ann. Oncol. 22 (2011)1736–1747.
[11]
Paik S, Tang G, Shak S, Kim C, Baker J, Kim W, et al. Gene expression and benefit of chemotherapy in women with node negative, estrogen receptor-positive breast cancer, J. Clin. Oncol. 24(2006)3726–3734.
[12]
Gianni L., Zambetti M, Clark K, Baker J, Cronin M, Wu J et al., Gene expression profiles in paraffin-embedded core biopsy tissue predict response to chemotherapy in women with locally advanced breast cancer, J. Clin. Oncol. 23(2005)7265–7277.
[13]
Burcombe RJ, Makris A, Richman PI, Daley FM, Noble S, Pittam M, et al. 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): 147e55.
[14]
Lee SH, Chung MA, Quddus MR, Steinhoff MM, Cady B. The effect of neoadjuvant chemotherapy on estrogen and progesterone receptor expression and hormone receptor status in breast cancer. Am J Surg 2003; 186:348- 350.
[15]
Kasami M, Uematsu T, Honda M, Yabuzaki T, Sanuki J, Uchida Y, et al. Comparison of estrogen receptor, progesterone receptor and Her-2 status in breast cancer pre- and post neoadjuvant chemotherapy. Breast 2008; 17(5):523e7.
[16]
Hurley J, Doliny P, Reis I, Silva O, Gomez-Fernandez C, Velez P, et al. Docetaxel, cisplatin, and trastuzumab as primary systemic therapy for human epidermal growth factor receptor 2- positive locally advanced breast cancer. J Clin Oncol 2006; 24(12):1831e8.
[17]
Sinn H. P, Schmid H, Junkermann H , Huober J, Leppien G, Kaufmann M, etal. Histologic regression of breast cancer after primary (neoadjuvant) chemotherapy , GeburtshilfeFrauen- heilkund. 54(1994)552–558.
[18]
Allred DC, Bustamante MA, Daniel CO, Gaskill HV, Cruz AB Jr. Immunocytochemical analysis of estrogen receptors in human breast carcinomas. Evaluation of 130 cases and review of the literature regarding concordance with biochemical assay and clinical relevance. Arch Surg 1990; 125:107-13.
[19]
Bustreo S, Osella-Abate S, Cassoni P, Donadio M, Airoldi M, Pedani F, et al. Optimal Ki67 cut-off for luminal breast cancer prognostic evaluation: a large case series study with a long-term follow-up, Breast Cancer Res Treat (2016) 157:363–371 .
[20]
Beresford MJ, Harris AL, Ah-See M, Daley F, Padhani AR, Makris A. The relationship of the neo-angiogenic marker, endoglin, with re­sponse to neoadjuvant chemotherapy in breast cancer. Br J Cancer 2006; 95: 1683-1688.
[21]
Jin G, Han Y, Liu C, Chen L, Ding B, Xuan S, et al. Evaluation of biomarker changes after administration of various neoadjuvant chemotherapies in breast cancer. Int J Clin Exp Pathol 2015; 8(1):914-921.
[22]
Piper G, Patel N, Patel J, Malay M, Julian T. Neoadjuvant chemotherapy for locally advanced breast cancer results in alterations in pre- operative tumor marker status, Am. Surg.70(2004)1103–1106.
[23]
Neubauer H, Gall C, Vogel U, Hornung R, Wallwiener D, Solomayer E etal. Changes in tumour biological markers during primary systemic chemotherapy (PST), AnticancerRes. 28 (2008) 1797–1804.
[24]
VandeVen S, Smit V, Dekker T, Nortier J, Kroep J, Discordances in ER, PR and HER2 receptors after neoadjuvant chemotherapy in breast cancer, Cancer Treat. Rev. 37 (2011) 422–430.
[25]
Gahlaut R , Bennett A, Fatayer H, Dall B, Sharma N , Velikova G , et al. Effect of neoadjuvant chemotherapy on breast cancer phenotype, ER/PR and HER2 expression -Implications for the practising oncologist. European Journal of Cancer 60 (2016) 40e48.
[26]
Ozmen V , Atasoy A, Bozdogan A, Dincer M, Eralp Y, Tuzlali S. Prognostic value of receptor status change following neoadjuvant chemotherapy in locally advanced breast cancer. Cancer Treatment Communications 4 (2015)89–95.
[27]
Trifunovic J, Memisevic N, Nikolin B, Salma S, Dugandzija T, Vidovic V. Modulatory effect of neoadjuvant chemotherapy on the prognosis of patients with breast cancer. JBUON 2017; 22(3): 638-643.
[28]
Yang L, Zhong X, Pu T, Qiu Y, Ye F, Bu H. Clinical significance and prognostic value of receptor conversion in hormone receptor positive breast cancers after neoadjuvant chemotherapy. World J Surg Oncol. 2018; 16: 51.
[29]
Shubham S, Maan P, Singh M, and Bhardwaj M. Invasive Ductal Carcinoma Breast: How Neoadjuvant Chemotherapy Affects the Status of Estrogen Receptor, Progesterone Receptor and HER2/Neu-A Tertiary Care Centre Study. J Clin Diagn Res. 2017 Jul; 11(7): EC06–EC08.
[30]
Reddy O and Apple S. Breast Cancer Biomarker Changes after Neoadjuvant Chemotherapy: A Single Institution Experience and Literature Review Clinics in Oncology 2017 | Volume 2 | Article 1245.
[31]
Avci N, Deligonul A, Tolunay S, Cubukcu E, Fatih Olmez O, Ulas A, et al. Neoadjuvant chemotherapy-induced changes in immunohistochemical expression of estrogen receptor, progesterone receptor, HER2, and Ki-67 in patients with breast cancer. J BUON. 2015 Jan-Feb; 20 (1):45-9.
[32]
Pedrini JL, Savaris RF, Schorr MC, Cambruzi E, Grudzinski M, Zettler CG. The effect of neoadjuvant chemotherapy on hormone receptor status, HER2/neu and prolactin in breast cancer. Tumouri. 2011; 97 (6):704–10.
[33]
Hawkins RA, Tesdale AL, Anderson ED, Levack PA, Chetty U, Forrest AP. Does the oestrogen receptor concentration of a breast cancer change during systemic therapy? Br J Cancer 1990; 61(6):877e80.
[34]
Yang YF, Liao YY, Li LQ, Xie SR, Xie YF, Peng NF. Changes in ER, PR and HER2 receptors status after neoadjuvant chemotherapy in breast cancer. Pathol Res Pract 2013; 209(12):797e802.
[35]
Cockburn A, Yan J, Rahardja D, Euhus D, Peng Y, Fang Y, et al. Modulatory effect of neoadjuvant chemotherapy on biomarkers expression; assessment by digital image analysis and relationship to residual cancer burden in patients with invasive breast cancer. Hum Pathol 2014; 45(2):249e58.
[36]
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):141e6.
[37]
Hirata T, Shimizu C, Yonemori K, Hirakawa A, Kouno T, Tamura K, et al. Change in the hormone receptor status following administration of neoadjuvant chemotherapy and its impact on the long-term outcome in patients with primary breast cancer. Br J Cancer 2009; 101(9):1529e36.
[38]
Vincent-Salomon A, Jouve M, Genin P, Freneaux P, Sigal- Zafrani B, Caly M, et al. HER2 status in patients with breast carcinoma is not modified selectively by preoperative chemotherapy and is stable during the metastatic process. Cancer 2002; 94(8):2169e73.
[39]
Mittendorf EA, Wu Y, Scaltriti M, Meric-Bernstam F, Hunt KK, Dawood S, et al. Loss of HER2 amplification following trastuzumab-based neoadjuvant systemic therapy and survival outcomes. Clin Cancer Res 2009; 15 (23):7381e8.
[40]
Bines J, Oleske DM, Cobleigh MA. Ovarian function in premenopausal Women treated with adjuvant chemotherapy for breast cancer. J Clin Oncol 1996; 14 (5):1718e29.
[41]
Dati C, Antoniotti S, Taverna D, Perroteau I, De Bortoli M. Inhibition of c-erbB-2 oncogene expression by estrogens in human breast cancer cells. Oncogene 1990; 5(7):1001e6.
[42]
Van Poznak C, Somerfield MR, Bast RC, Cristofanilli M, Goetz MP, Gonzalez-Angulo AM, et al. Use of Biomarkers to Guide Decisions on Systemic Therapy for Women With Metastatic Breast Cancer: American Society of Clinical Oncology Clinical Practice Guideline. J Clin Oncol. 2015; 33:2695–704.
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