Resistant cells show greater proliferation and exhibit changes in ER and PR expression. (A) Cell proliferation assay of UACC-812 and BT474 parental and resistant (R) cells. Cells were treated with trastuzumab (T, 10 μg/ml), lapatinib (L, 1 μM), or trastuzumab plus lapatinib (L + T). After six days, viable cells were visualized by methylene blue staining and photographed. (B) Fold changes in cell growth of UACC-812 and BT474 parental and resistant cells with or without the respective anti-HER2 therapies, following six days of treatment. Cell numbers were quantified by absorbance at 655 nm and normalized against Day 0. Significance between groups was determined by multiple comparisons using the Sidak method (*P < 0.0001, P:T versus TR:T, P:L versus LR:L, or P:L + T versus LTR:L + T for both models). (C) Immunohistochemical detection of ER and PR in BT474 and UACC-812 parental and distinct resistant clones.