Development of preclinical models of human BT474 and MDA-MB-361 breast cancer that endogenously overexpress HER2 and that respond to trastuzumab.

e11061 Background: The anti-Her-2 antibody trastuzumab can be effectively combined with chemotherapy to treat Her-2 positive metastatic breast cancers. However, Her-2 positive breast cancers readily develop resistance to trastuzumab based therapies, and new models are needed to study such resistance, and to find new therapeutic options. Methods: We began the in vivo selection of human Her-2 positive breast cancer cell lines, BT474 and MDA-MB-361, in Severely Compromised Immunodeficient (SCID) mice. Tumor cells were implanted orthotopically into the mammary fat pad of SCID mice, and resulting tumors were serially passaged into new hosts over a 3 year period. Results: The resulting variants grow rapidly in SCID mice. Variants of both BT474 and MDA-MB-361 respond in vivo to trastuzumab monotherapy (20mg/kg twice weekly, i.p.) compared to controls (p<0.05). After 2-6 months of trastuzumab monotherapy, all variants developed resistance to trastuzumab; such resistant variants were adapted to tissue culture. BT4...