Type 2 Diabetes and Breast Cancer: The Interplay between Impaired Glucose Metabolism and Oxidant Stress

Table 2

Metformin use and survival outcomes of breast cancer patients.

Reference	Study design	Study population^a	BC type	Mean age (years)	Metformin versus non-metformin	Study findings
Currie et al., 2012 [82]	Retrospective	1182	All	NA	NA	OS: HR 0.96 (95% CI: 0.67–1.37)
Bayraktar et al., 2012 [83]	Retrospective	130	Triple negative	52	63 versus 67	RFS: HR: 1.37 (95% CI: 0.78–2.40); OS: HR: 1.22 (95% CI: 0.66–2.28)
He et al., 2012 [84]	Retrospective	154	HER2+	55	88 versus 66	OS: HR 0.52 (95% CI: 0.28–0.97)
Peeters et al., 2013 [85]	Retrospective	1058	All	NA	508 versus 550	OS: HR 0.74 (95% CI: 0.58–0.96)
Lega et al., 2013 [86]	Population-based	2361	All	77	1094 versus 1267	OS: HR 0.97 (95% CI: 0.92–1.02)
Hou et al., 2013 [87]	Retrospective	1013	All	NA	419 versus 594	NA^b
Oppong et al., 2014 [88]	Retrospective	145	All	61	76 versus 65	RFS: HR 0.86 (95% CI: 0.38–1.90)
Xiao et al., 2014 [89]	Retrospective	680	Luminal	NA	275 versus 405^c	OS luminal A: HR 3.58 (95% CI: 1.51–8.51); OS luminal B (Ki67): HR 3.23 (95% CI: 1.84–5.68); OS luminal B (Her2+): HR 2.034 (95% CI: 1.02–4.06)
Kim et al., 2015 [90]	Retrospective	386	ER/PR status; Her2 status	55/59	202 versus 184	CSS ER+/PR+ Her2+: HR 6.51 (95% CI: 2.06–20.6); DFS ER+/PR+ Her2+: HR 5.37 (95% CI: 1.88–15.3)
Vissers et al., 2015 [91]	Retrospective	1057	All	71	688 versus 369	OS: HR 0.47 (95% CI: 0.26–0.82)

BC: breast cancer; NA: not available; OS: overall survival; HR: hazard ratio; RFS: relapse-free survival; ER: estrogens receptors; PR: progesterone receptors; CSS: cancer specific survival; DFS: disease-free survival.
WHI: Women’s Health Initiative, comprising four clinical trials and an observational study; ^aIncluding only breast cancer patients with diabetes; ^bHR 0.76 (95% CI: 0.6–0.99) for OS of metformin-treated patients compared to nondiabetic patients.
^cNon-metformin versus metformin group.