(A-E) Adult NSG or (F-G) humanized mice were engrafted with 5×104 MDA-MB-231 breast cancer cells by intracardiac injection. Randomized tumor-bearing mice and treated with either 10 mg/kg of the indicted therapeutic mAb or CTX (100 mg/kg) as single agents or in combination on day 10, 15, and 20 post tumor engraftment. Bioluminescence intensities were assessed by IVIS imaging on the indicated days. (A) Representative mouse images and (B) quantifications of bioluminescence intensity shown (mean+SD). (C) Representative H&E stains of femur sections (40x) of mice at day 20 after tumor engraftment. Inserts: tibia and femur from representative mice. (D) Bone lesions were scanned by micro CT at the indicated days; sizes of lesions (mean ±SD) are shown overtime. (E) Survival of cohorts of mice with different treatments. Trastuzumab and cetuximab alone or plus CTX were used, as indicated. (F) Representative bioluminescent images and (G) quantifications of tumor-bearing humanized mice (mean+SD). 3–5 mice/group, repeated at least 3 times for each experiment; **p<0.001, **p<0.001 by Mann-Whitney test.