World J Oncol

World Journal of Oncology, ISSN 1920-4531 print, 1920-454X online, Open Access

Article copyright, the authors; Journal compilation copyright, World J Oncol and Elmer Press Inc

Journal website http://www.wjon.org

Original Article

Volume 11, Number 1, February 2020, pages 23-32

The Effect of Metformin on the Clinicopathological Features of Breast Cancer With Type 2 Diabetes

Figure 1. Expression of ER, PR, HER-2 and Ki-67 in breast cancer. ER: estrogen receptor; PR: progesterone receptor; HER-2: human epidermal growth factor receptor-2.

Figure 2. FISH results of breast cancer tissues. (a) HER-2 negative (punctuate distribution, HER-2/CSP17 ratio of 1.2); (b) HER-2 positive (punctuate distribution, HER-2/CSP17 ratio of 2.2); (c) HER-2 positive (cluster distribution). FISH: fluorescence in situ hybridization; HER-2: human epidermal growth factor receptor-2.

Figure 3. Expression of EGFR, MMP-2, E-cadherin and N-cadherin in breast cancer. EGFR: epidermal growth factor receptor; MMP-2: matrix metalloproteinase-2.

**Table 1.** A Summary of the Use of Hypoglycemic Drugs in 89 Breast Cancer Patients With T2DM
Hypoglycemic drugs	Number of cases	%
T2DM: type 2 diabetes mellitus.
Sulfonylureas	19	18.6
Insulin	14	13.7
Thiazolidinediones	2	1.9
Acarbose	4	3.9
Metformin alone	10	9.8
Metformin + insulin	2	1.9
Metformin + glinides	4	3.9
Metformin + thiazolidinedione	1	1.0
Metformin + sulfonylureas	15	14.7
Metformin + acarbose	1	1.0
Sulfonylureas + thiazolidinediones	1	1.0
Insulin + sulfonylureas	1	1.0
Herbal medicine	2	1.9
Diet control	2	1.9
Unknown medication	6	5.9
No drug treatment	5	4.9

Table 1. A Summary of the Use of Hypoglycemic Drugs in 89 Breast Cancer Patients With T2DM

Hypoglycemic drugs

Number of cases

T2DM: type 2 diabetes mellitus.

Sulfonylureas

18.6

Insulin

13.7

Thiazolidinediones

1.9

Acarbose

3.9

Metformin alone

9.8

Metformin + insulin

1.9

Metformin + glinides

3.9

Metformin + thiazolidinedione

1.0

Metformin + sulfonylureas

14.7

Metformin + acarbose

1.0

Sulfonylureas + thiazolidinediones

1.0

Insulin + sulfonylureas

1.0

Herbal medicine

1.9

Diet control

1.9

Unknown medication

5.9

No drug treatment

4.9

**Table 2.** Comparison of General Situation Between Metformin and Control Groups
Observation indicators	Metformin group	Control group	t	P
Age	63.42 ± 8.24	65.01 ± 7.45	0.627	> 0.05
BMI	23.21 ± 3.26	25.15 ± 3.67	1.281	> 0.05
T2DM course	4.52 ± 2.15	5.10 ± 3.08	1.560	> 0.05

Table 2. Comparison of General Situation Between Metformin and Control Groups

Observation indicators

Metformin group

Control group

Age

63.42 ± 8.24

65.01 ± 7.45

0.627

> 0.05

BMI

23.21 ± 3.26

25.15 ± 3.67

1.281

> 0.05

T2DM course

4.52 ± 2.15

5.10 ± 3.08

1.560

> 0.05

**Table 3.** Comparison of Clinicopathological Features Between Metformin and Control Groups
Clinicopathological features	Metformin group	Control group (N = 56)	χ²	P
ER: estrogen receptor; PR: progesterone receptor; HER-2: human epidermal growth factor receptor-2. *P < 0.05.
Tumor size
T ≤ 2 cm	7 (21.2%)	10 (17.9%)	0.151	0.697
T > 2 cm	26 (78.8%)	46 (82.1%)
Lymph node
Negative	16 (48.5%)	12 (16.1%)	7.049	0.008*
Positive	17 (51.5%)	44 (78.6%)
Clinical stage
I	6 (18.2%)	9 (16.1%)	0.066	0.797
II, III	27 (81.8%)	47 (83.9%)
Histological grade
I	8 (24.2%)	8 (14.3%)	1.396	0.237
II, III	25 (75.8%)	48 (85.7%)
ER status
Negative	14 (42.4%)	31 (55.4%)	2.796	0.095
Positive	19 (57.6%)	25 (44.6%)
PR status
Negative	13 (39.4%)	34 (60.7%)	3.787	0.052
Positive	20 (60.6%)	22 (39.3%)
HER-2 status
Negative	28 (84.8%)	41 (73.2%)	1.613	0.204
Positive	5 (15.2%)	15 (26.8%)
Ki-67
< 14%	21 (63.6%)	21 (37.5%)	5.692	0.017*
≥ 14%	12 (36.4%)	35 (62.5%)
Molecular typing
Luminal	25 (75.8%)	30 (53.6%)	4.329	0.037*
Others	8 (24.2%)	26 (46.4%)

Table 3. Comparison of Clinicopathological Features Between Metformin and Control Groups

Clinicopathological features

Metformin group

Control group (N = 56)

χ²

ER: estrogen receptor; PR: progesterone receptor; HER-2: human epidermal growth factor receptor-2. *P < 0.05.

Tumor size

T ≤ 2 cm

7 (21.2%)

10 (17.9%)

0.151

0.697

T > 2 cm

26 (78.8%)

46 (82.1%)

Lymph node

Negative

16 (48.5%)

12 (16.1%)

7.049

0.008*

Positive

17 (51.5%)

44 (78.6%)

Clinical stage

6 (18.2%)

9 (16.1%)

0.066

0.797

II, III

27 (81.8%)

47 (83.9%)

Histological grade

8 (24.2%)

8 (14.3%)

1.396

0.237

II, III

25 (75.8%)

48 (85.7%)

ER status

Negative

14 (42.4%)

31 (55.4%)

2.796

0.095

Positive

19 (57.6%)

25 (44.6%)

PR status

Negative

13 (39.4%)

34 (60.7%)

3.787

0.052

Positive

20 (60.6%)

22 (39.3%)

HER-2 status

Negative

28 (84.8%)

41 (73.2%)

1.613

0.204

Positive

5 (15.2%)

15 (26.8%)

Ki-67

< 14%

21 (63.6%)

21 (37.5%)

5.692

0.017*

≥ 14%

12 (36.4%)

35 (62.5%)

Molecular typing

Luminal

25 (75.8%)

30 (53.6%)

4.329

0.037*

Others

8 (24.2%)

26 (46.4%)

**Table 4.** Comparison of Immunohistochemical Indicators Between Metformin and Control Groups
Immunohistochemical indicators	Metformin group	Control group	χ²	P
EGFR: epidermal growth factor receptor; MMP-2: matrix metalloproteinase-2. *P < 0.05.
EGFR
Negative	13 (39.4%)	17 (30.4%)	0.759	0.384
Positive	20 (60.6%)	39 (69.6%)
E-cadherin
Negative	11 (33.3%)	30 (53.6%)	3.423	0.064
Positive	22 (66.7%)	26 (46.4%)
N-cadherin
Negative	28 (84.8%)	43 (76.8%)	0.837	0.360
Positive	5 (15.2%)	13 (23.2%)
MMP-2
Negative	23 (69.7%)	24 (42.9%)	6.002	0.014*
Positive	10 (30.3%)	32 (57.1%)

Table 4. Comparison of Immunohistochemical Indicators Between Metformin and Control Groups

Immunohistochemical indicators

Metformin group

Control group

χ²

EGFR: epidermal growth factor receptor; MMP-2: matrix metalloproteinase-2. *P < 0.05.

EGFR

Negative

13 (39.4%)

17 (30.4%)

0.759

0.384

Positive

20 (60.6%)

39 (69.6%)

E-cadherin

Negative

11 (33.3%)

30 (53.6%)

3.423

0.064

Positive

22 (66.7%)

26 (46.4%)

N-cadherin

Negative

28 (84.8%)

43 (76.8%)

0.837

0.360

Positive

5 (15.2%)

13 (23.2%)

MMP-2

Negative

23 (69.7%)

24 (42.9%)

6.002

0.014*

Positive

10 (30.3%)

32 (57.1%)

**Table 5.** Comparison of Tumor Metastasis of Metformin and Control Groups
Follow-up results	Total number	Metformin group	Control group
Local recurrence	2	0	2
Cutaneous metastasis	1	0	1
Bone metastases	2	1	1
Ipsilateral regional lymph node metastasis	2	1	1
Hepatic metastases	1	0	1
Pulmonary metastasis	2	1	1
Brain metastases	1	0	1
Multiple metastasis	2	1	1
Total	13	4	9

Table 5. Comparison of Tumor Metastasis of Metformin and Control Groups

Follow-up results

Total number

Metformin group

Control group

Local recurrence

Cutaneous metastasis

Bone metastases

Ipsilateral regional lymph node metastasis

Hepatic metastases

Pulmonary metastasis

Brain metastases

Multiple metastasis

Total