Table 1 Metformin trials in non-diabetic breast cancer patients

Goodwin et al. 2008 [1]

22

Early BC patients; insulin >45 pmol/L

Adjuvant

Single arm

500 mg tid × 6 mos

↓

○

↓

↓

Hadad et al., 2011 [2], Hadad et al. 2015 [3]

8 + 47

Operable invasive BC

Neoadjuvant window

Metf versus ctrl (no metf)

500 mg qd × 1 wk, then 1000 mg bid × 1 wk

○ in metf, ↑ in ctrl

↓ in metf, ○ in ctrl

↓Cleaved Caspase-3

NS ↓ IR; ↓ pAkt

↑p-AMPK

Bonanni et al. 2012 [4], Cazzaniga et al. 2013 [5], DeCensi et al. 2014 [6]

200

Operable BC

Neoadjuvant window

Metf versus ctrl (placebo)

850 mg bid × 4 wks

↓ in BMI > 27

NS ↓ in BMI > 27

○ metf versus ctrl; NS ↓ in HOMA > 2.8 and NS ↑ in HOMA < 2.8

TUNEL ↑ in both metf and ctrl

↓IGFBP-1

Kalinsky et al. 2014 [7]

35

Ov/Ob invasive BC or DCIS versus matched untreated historical ctrl

Neoadjuvant window

Single arm

500 mg am and 1000 mg pm, 2–4 wks (avg = 22 days)

↓

○

NS ↓

NS ↓

○

○ IGFBP-3

Goodwin et al. 2015 [8]

3,649

Treated early BC

Adjuvant

Metf versus ctrl (placebo)

850 mg bid × 5 yrs (results reported after 6 mos)

↓

↓

↓

↓

Niraula et al. 2012 [9], Dowling et al. 2015 [10]

39

Operable BC

Neoadjuvant window

Single arm

500 mg tid 13–40 days (avg = 18)

↓

↓

NS ↓

↓

Largest ↓ in patients with largest ↓ in insulin, IR, and pAkt

TUNEL ↑

↓ IR, pAkt, and pERK1/2

↓ pAMPK and pACC; all tumors expressed OCT1