A. Mice bearing MCF7 HER2-18 tumor xenografts were subjected to estrogen deprivation (ED) until development of resistance, which was associated with complete loss of ER expression (18). At that time, the combination of trastuzumab, pertuzumab, and gefitinib (TPG) was added to ED. Anti-HER therapy induced tumor regression in 53% of mice (responders), whereas the remaining tumors continued to grow despite the inhibition of both ER and HER pathways. Restoration of ER expression was significantly associated with tumor response.
B. Mice bearing MCF7 HER2-18 tumor xenografts were randomized at the time of ED-resistance to receive TPG with or without continuing endocrine therapy (ED). The combination of TPG + ED was able to significantly delay tumor growth compared to TPG + E2 in the responders, but not in the non-responders.