Supplementary Table S1 Clinical exposure for palbociclib, fulvestrant and chemotherapeutic agents used in this study.

  Palbociclib (1)* Paclitaxel (2)* Doxorubicin (3)* Fulvestrant (4)*

Clinical Dose 125 mg 175 mg/m2 60 mg/m2 500 mg/5ml

Cmax 202 nM 0.43 µM 1.16 µM 46 nM

Cave calculation 144 nM 0.078 µM 0.25 µM 30 nM

based on AUC (AUC 0-24hr 1982 ng.h/ml) (AUC 0-120hr 7993ng.h/ml) (AUC 0-24hr 358ng.h/ml) (AUC 0-15day 13100 ng.hr/ml)

* Numbers in parenthesis indicate reference number.

Supplementary Table S2. Cell cycle analysis in human bone marrow mononuclear cells treated with palbociclib for 4 days.

  Dead Cell G1 Phase S Phase G2/M Phase

Vehicle 6.25% (± 0.59%) 53.96% (± 2.33%) 27.93% (± 0.98%) 11.75% (± 1.91%)

Palbociclib 0.1uM 4.32% (± 0.84%) 60.98% (± 3.32%) 20.61% (± 0.84%) 13.19% (± 1.72%)

Palbociclib 0.3uM 4.66% (± 0.14%) 67.4% (± 2.04%) 16.10% (± 1.49%) 7.04% (± 0.39%)

Palbociclib 1uM 4.68% (± 1.17%) 79.23% (± 1.17%) 9.99% (± 2.59%) 4.55% (± 0.73%)

Supplementary Figure S1

A B

Supplementary Figure S2

Supplementary Figure S3

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Supplementary Figure S4