Abstract P2-05-11: Genetic profiling of breast cancer confirms a pivotal role of EGFR pathway in the development of acquired resistance to tamoxifen
Authors: Rabab M Gaafar, Abeer A Bahnasy, Osman M Mansour, Nasr M Allahloubi, Ibrahim A Malash, Sabry M Shaarawy
Journal: Cancer Research (2015)

Abstract Background: Acquisition of resistance to tamoxifen remains a major drawback in the treatment of oestrogen receptor (ER)-positive breast cancers. Aberrant expressions of some genes in the EGFR pathway were associated to the acquisition of resistance in some studies. Patients and methods: This prospective study was carried out on 157 female patients with hormone receptor positive, locally recurrent inoperable and/or metastatic breast cancer who presented to the National Cancer Institute, Cairo University during the period from October 2010 to October 2012. All patients received tamoxifen. Patients were divided into tamoxifen responsive and refractory groups according to their response to therapy. In an attempt to understand the contribution of EGFR pathway to the development of resistance to Tamoxifen, we assessed the genetic profile of the EGFR pathway genes in the 2 groups. RNA was extracted from tumor and normal tissue samples obtained from all patients and the expression level of 92 genes was evaluated using the SABioscience array (Qiagen) with four house-keeping genes. Results: Age ranged between 29 and 79 years but age ≤ 50 or &amp;gt; 50 did not correlate to resistance. Evaluation of Hormone receptor status showed that 58.59% were positive for both ER and PR, 32.48% were ER positive, PR negative and 8.91% ER negative PR positive. Neither hormone receptor status nor nuclear grade was correlated to drug resistance. There was a strong correlation between response to tamoxifen and disease site as patients with bone only disease demonstrated noticeable good and maintained response compared to those who had visceral involvement (p- 0.005). The expression levels of all genes were assessed in both studied groups: the responders (the control) and the refractory (tested) groups. Fifty six genes were differentially over-expressed in the refractory group compared to the responding group, among which only JAK1, COL1A1, GAB1, FN1 and MKNK1 showed a significant difference between responders and refractory groups. Thirty four genes were differentially expressed (reduced expression) in the refractory compared to the responders. Moreover, CYP2D6 *3, *4 were significantly prevalent in the refractory group (86.6%), whereas variants *10/*10 and *10/*3 were more common in the in the responding group (85.5%) (p = 0.027) Conclusion: A panel of 5 genes (M JAK1, COL1A1, GAB1, FN1 and MKNK1) in EGFR pathway together with CYP2D6 polymorphisms could be used to predict patient’s response to tamoxifen though this has to be verified in an extended study including larger sample. Citation Format: Rabab M Gaafar, Abeer A Bahnasy, Osman M Mansour, Nasr M Allahloubi, Ibrahim A Malash, Sabry M Shaarawy. Genetic profiling of breast cancer confirms a pivotal role of EGFR pathway in the development of acquired resistance to tamoxifen [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P2-05-11.