Preventive effects of the EGFr inhibitor erlotinib in ER+ methylnitrosourea (MNU) induced and in ER- MMTV/Neu/P53KO mammary cancer models.

Abstract #1112 The preventive/therapeutic efficacies of Erlotinib in both ER + and ER - models of breast cancer in rats and mice, respectively, were evaluated. For the ER + model, female Sprague-Dawley rats were administered MNU at 50 days of age. Beginning five days later, Erlotinib was administered 7x/week for the remainder of the study. Daily administration of Erlotinib in a prevention setting at 4 and 1.33 mg/kg BW/day reduced tumor multiplicity by 72 and 35%, respectively; doses >6 mg/kg BW/day decreased cancers by >90%. When rats with palpable mammary cancers were treated for six weeks with 4 mg/kg BW/day of Erlotinib, most of the tumors showed highly significantly regressions. Similarly, when rats bearing palpable mammary cancers were treated with Erlotinib for 5 days (3 or 1 mg/kg BW/day), large decreases in tumor cell proliferation and alterations in expression of phosphorylated EGFr, AKT, ERK and SHC were observed. In additional studies, the preventive effect of Erlotinib in a MMTV/Neu/P53KO bitransgenic model was examined. These mice develop ER - cancers which overexpress Neu and have an alteration in P53. These changes are characteristic of ER - human breast cancers. An initial experiment showed that Erlotinib (50 mg/Kg BW/day) was also effective as a preventive agent in this model. Effects of this agent on proliferation and altered expression of phosphorylated EGFr, AKT, ERK and SHC are in progress. Our results showing efficacy of the EGFr inhibitor Erlotinib in ER + mammary cancers are in agreement with a clinical study of early stage human ER + breast cancer showing that the EGFr inhibitor Gefitinib is highly effective in ER+/EGFr+ tumors (Polychronis, et al., Lancet Oncolo. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 1112.