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Biological markers associated with response to gefitinib (ZD1839) in patients with breast cancer [Abstract]

Gutteridge, E., Gee, Julia Margaret Wendy, Nicholson, Robert Ian and Robertson, J. F. R. 2004. Biological markers associated with response to gefitinib (ZD1839) in patients with breast cancer [Abstract]. Journal of Clinical Oncology 22 (14S) , 648.

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Abstract

Background: In patients (pts) with breast cancer, increased epidermal growth factor receptor (EGFR)/HER2 signalling is associated with de novo hormone resistance and oestrogen receptor (ER)-negative phenotypes. EGFR signalling is a key growth regulator in ER-positive acquired tamoxifen-resistant (TAM-R) models where EGFR-TKIs (EGFR tyrosine kinase inhibitors) are potent inhibitory agents. Preliminary clinical data show that the EGFR-TKI gefitinib (‘Iressa’, ZD1839) may be an effective treatment for TAM-R breast cancer (Proc Am Soc Clin Oncol 2003; 22: 7, abs 23). Here we report on expression of ER, EGFR, HER2 and insulin-like growth factor receptor (IGF-1R) in pts enrolled in a Phase II study of gefitinib. Methods: Two groups of pts were recruited: an ER-positive TAM-R group (n=20) and an ER-negative group (n=27). Pts received oral gefitinib 500 mg/day. Immunostaining was performed for ER and EGFR expression and HER2/IGF-1R expression/phosphorylation, and was semiquantified by HScore. With the exception of ER, median HScore was used as the positivity cut-off point. SPSS statistical analysis was used to determine if marker expression predicted gefitinib response by UICC criteria at 6 months or time to progression (TTP). Results: Pretreatment samples were available for 35 pts: 13 ER-positive and 22 ER-negative. Although responders were seen in both groups, responses were more frequently observed in ER-positive (82%) than ER-negative pts (13%). All responders expressed EGFR (median HScore 30, range 10-65) but a higher incidence of progressive disease (p=0.015) and a shorter TTP (p=0.012) were recorded in pts with high EGFR expression (clinical benefit median 36.5, range 10-160; progressive disease median 80, range 5-230). HER2 expression was similar in ER-positive TAM-R pts (54.5%) and ER-negative pts (47.6%). In ER-positive pts, high levels of HER2 did not preclude a response to gefitinib. Expression of IGF-1R did not predict response. Conclusion: Further biomarker studies, ongoing in these patients, are required to characterise predictors of response. 'Iressa' is a trademark of the AstraZeneca group of companies

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Pharmacy
Subjects: R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
R Medicine > RM Therapeutics. Pharmacology
Additional Information: Abstract presentation from the 2004 ASCO Annual Meeting
Publisher: Grune and Stratton
ISSN: 0732-183X
Related URLs:
Last Modified: 04 Jun 2017 03:08
URI: http://orca-mwe.cf.ac.uk/id/eprint/17223

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