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Claudin -low/Basal

a. Figure 1. b. HER2-amplified. Claudin -low/Basal . Luminal. e. c. d. f. *. *. *. *. Figure 2. d. b. c. a. *. *. f. e. g. P<0.001. P=0.56. P=0.009. a. Figure 3. b. MCF7 growth with early treatment. MCF7 growth with late treatment. d. c. f. e. g. Figure 4. *.

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Claudin -low/Basal

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  1. a Figure 1 b HER2-amplified Claudin-low/Basal Luminal e c d f * * * *

  2. Figure 2 d b c a * * f e g P<0.001 P=0.56 P=0.009

  3. a Figure 3 b MCF7 growth with early treatment MCF7 growth with late treatment d c f e g

  4. Figure 4 * * c d a b

  5. Figure 5 c b d Late treatment * * * Early treatment ALDH HER2 a Fat pad Tibia h g e f * * k j i HER2 ALDH1 Tibia control Tibia Trastuzumab

  6. Figure 6 Bone b a Primary Luminal HER2-amplified d c Metastatic-Advanced Clinical Endpoint Tumor Regrassion Micrometastatic-Adjuvant Clinical Endpoint Reduction in Tumor Recurrence Breast Tumors HER2+++ (Amplified) YES YES HER2+ or ++ (Non-amplified) NO YES Basal HER2- ER- NO NO

  7. Supplementary 1 a b

  8. MCF7 ZR75-1 Supplementary 2 * a b *

  9. Supplementary 3 b a

  10. Supplementary 4 MCF7_Her2 Isotype control Coculture+Denosumab_HER2 a a 0.1% 26.13% Osteocyte Coculture_HER2 b b HER2 HER2 shHER-2 shHER-2 shVector shVector Actin Actin 44.9% 30.13%

  11. Supplementary 5 a b Luminal HER2 amplified

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