The effects of gefitinib in tamoxifen-resistant and hormone-insensitive breast cancer: a phase II study

Gutteridge, Eleanor, Agrawal, Amit, Nicholson, Robert Ian, Cheung, Kwok Leung, Robertson, John and Gee, Julia Margaret Wendy ORCID: https://orcid.org/0000-0001-6483-2015 2010. The effects of gefitinib in tamoxifen-resistant and hormone-insensitive breast cancer: a phase II study. International Journal of Cancer 126 (8) , pp. 1806-1816. 10.1002/ijc.24884

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Abstract

Estrogen receptor (ER)-positive acquired tamoxifen-resistant (TAM-R) MCF-7 breast cancer cell lines exhibit epidermal growth factor receptor (EGFR) expression/signaling and are growth-inhibited by gefitinib (IRESSA). We examined the effect of gefitinib on ER-positive TAM-R and ER-negative hormone-insensitive breast cancer in a Phase II study. Fifty-four patients with breast cancer [ER-positive/acquired TAM-R (n = 28); ER-negative (n = 26)] received oral gefitinib 500 mg/day. Tumor biopsies were taken pre- (n = 28) and 8 weeks post-treatment (n = 14 matched samples). Gefitinib was well tolerated and the clinical benefit rate (objective response or stable disease >24 weeks) was 33.3% overall (n = 18/54), and 53.6 and 11.5% in ER-positive/TAM-R and ER-negative patients, respectively. Pretreatment ER and progesterone receptor-positivity were associated with response (p < 0.001 and 0.016, respectively) and longer progression-free survival (PFS; p= 0.001 and 0.013, respectively). All patients expressed EGFR, but high pretreatment levels predicted poorer outcome (p = 0.005) and shorter PFS (p = 0.012) with gefitinib. In patients with clinical benefit, reduced Ki67 staining during treatment (p = 0.024) was commonly observed, and those with >10% decline in EGFR phosphorylation demonstrated parallel decreases in ERK1/2 MAPK phosphorylation. Acquired tamoxifen resistance appears in part mediated through EGFR signaling and can be blocked with gefitinib

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Schools > Pharmacy
Subjects:	R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer) R Medicine > RM Therapeutics. Pharmacology
Uncontrolled Keywords:	EGFR-TKI ; breast cancer ; IRESSA ; gefitinib ; tamoxifen-resistant
Publisher:	John Wiley & Sons
ISSN:	0020-7136
Last Modified:	17 Oct 2022 10:00
URI:	https://orca.cardiff.ac.uk/id/eprint/6540

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