[Lani]

As expected (Baselga et al., 1998; Konecny et al.,
2006), both lapatinib and trastuzumab induced tumor
regression of BT474 cell-derived xenografts. All the mice
receiving the combination of lapatinib and trastuzumab
showed complete tumor remission after 10 days (day 23)
of treatment (Figure 5a). In these animals no tumor
relapse was observed after 8 months from the comple-
tion of therapy. Tumors derived from the animals
excluded at day 19 (6 days of treatment) were excised
and subjected to anti-HER2 immunohistochemistry
analysis. There was an increase in HER2 expression in
tumors treated with lapatinib alone and a decrease
of HER2 expression in trastuzumab-treated tumors as
compared with controls (Figure 5b). The degree of
decrease of HER2 expression did not reach its peak at
this point as treatment with trastuzumab for 16 days
resulted in a higher degree of HER2 downregulation
(data not shown). In the combination group, the effects
of lapatinib on HER2 accumulation were dominant over
those of trastuzumab (Figure 5b).