Metformin Efficacy on Proliferation Indices of Tumoral Cells in Non-Diabetic Patients with Invasive Breast Cancer Referring to the Cancer Institute of Iran
-
Sanambar Sadighi
,
Maasoumeh Saberian
,
Bita Behrouzi
,
Massoome Najafi
,
Issa Jahanzad
,
Ramesh Omranipour
Abstract
Background: Because of the decreasing effect of metformin on insulin resistance, it has been suggested as an anti-obesity and anti-cancer drug. So, we aimed to study the effect of metformin therapy on tumor cell proliferation in non-diabetic breast cancer patients.Methods: We conducted a prospective clinical trial and studied the effect of metformin therapy on the level of Ki67 as a measure of tumor cell proliferation. Our primary endpoint was to evaluate the changes in Ki67. The intervention group consisted of 25 non-diabetic breast cancer patients with no indication for neoadjuvant chemo- therapy. They were followed up from the time of biopsy to operation. Metformin (1500 mg/day) was prescribed in the intervention group from the date of diagnosis until the surgery (2.8 weeks). Controls were 20 early breast cancer patients who had been followed up with no prescription from biopsy until operation.Results: We could not find any statistically significant difference between the two groups regarding baseline clinical or tumor characteristics such as age, stage, grade, estrogen receptor, HER2 status or time, and type of surgery. However, the immuno- histochemistry (IHS) study showed a decrease in median Ki67 from 35.14 to 29.6 in the intervention group (P-value= 0.02). While an increase from 24.5 to 30.6 was detected in the control group (P-value= 0.02). Both of these changes were statistically significant. Although mild gastrointestinal symptoms were seen in approximately 50% of cases, generally, patients tolerated metformin well. There was a correlation between the score of HOMA, a metabolic factor, and the changes in KI67.Conclusion: Metformin prescription in a short period of time between biopsy and definitive surgery leads to the inhibition of breast cancer cell growth. We found a relationship between metformin anti-proliferative effect and glucose and insulin metabolism.
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13- Cazzaniga M, Decensi A, Pruneri G, et al. The effect of metformin on apoptosis in a breast cancer presurgical trial. Br J Cancer. 2013; 109:2792–2797.
14- Capasso I, Esposito E, Pentimalli F, Montella F, et al. Homeostasis model assessment to detect insulin resistance and identify patients at high risk of breast cancer development: National Cancer Institute of Naples experience. J Exp Clin Cancer Res. 2013; 32(1): 14.
15- Igwa E, Azman AZF, Nardin AJ, Mohtarrudin N. ASSOCIATION BETWEEN HOMA-IR AND CANCER. International J Public Health and Clin Sciences. 2015;2 (2): 21
16- Sadighi S, Zokaasadi M, Kasaeian A, maghsudi S, Kamranzadeh . The effect of immunohistochemically detected p53 accumulation in prognosis of breast cancer; A retrospective survey of outcome. PloS one, 2017 ;12(8): e0182444.
2- Carol E. DeSantis, Jiemin Ma, Mia M. Gaudet, Lisa A. Newman, Kimberly D. Miller, Ann Goding Sauer, Ahmedin Jemal, Rebecca L. Siegel. Breast cancer statistics 2019. CA: Cancer J. for Clinicians. 2019;69(6): 438-451
3-Freddie Bray ,Jacques Ferlay, Isabelle Soerjomataram, Rebecca L. Siegel ,Lindsey A. Torre,Ahmedin Jemal . Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries.
4- Carstensen B, Witte DR, Friis S. Cancer occurance in Danish diabetic patients: duration and insulin effects. Diabetologia. 2012;55(4): 948-958.
5- Tao Z, Shi A, Lu C, et al. Breast cancer: epidemiology and etiology. Cell Biochem. Biophysics. 2015;72: 333-338.
6- Behrouzi B, Mohagheghi MA, Sadighi S. Demographic Characteristics, Survival and Prognostic Factors of Early Breast Cancer Patients with Type 2 Diabetes Mellitus: A Hospital-Based Cohort Study. Asian Pac J Cancer Prev. 2016; 18(9): 2485-2491.
7- Noto H, Goto A, Tsujimoto T, Noda M. Cancer risk in diabetic patients treated with metformin: a systematic reviewe and meta-analysis.PloS one.2012: 7(3): e33411.
8- Faria J, Negalha G, Azevedo A, Martel F. Metformin and Breast Cancer: Molecular Targets. J Mammary Gland Biol Neoplasia. 2019. Jun;24 (2):111-123.
9- Sadighi S, Amanpour S, Behrouzi B, Khorgami Z, Muhammadnejad S. Lack of Metformin Effects on Different Molecular Subtypes of Breast Cancer under Normoglycemic Conditions: An in vitro Study. Asian Pac J Cancer Prev,2014; 15 (5), 2287-2290
10- Joshan MHK, Shing YK, Paca NP. Metformin as an adjuvant in breast cancer treatment. SAGE Open Medicine. 2019;7: 1-16
11- Hadad S, Iwamoto T, Jordan L, Purdie C, Bray S, Baker L, et al. Evidence for
biological effects of metformin in operable breast cancer: a pre-operative, window-of opportunity,
randomized trial. Breast cancer research and treatment. 2011;128 (3):783-94.
12- Niraulas S, Dowling RJ, Ernis M, Chang MC, Done SJ, et al. Metformin in early breast; a prospective window of opportunity neoadjuvant study. Breast Cancer Res Treat. 2012;135 (3); 821-830.
13- Cazzaniga M, Decensi A, Pruneri G, et al. The effect of metformin on apoptosis in a breast cancer presurgical trial. Br J Cancer. 2013; 109:2792–2797.
14- Capasso I, Esposito E, Pentimalli F, Montella F, et al. Homeostasis model assessment to detect insulin resistance and identify patients at high risk of breast cancer development: National Cancer Institute of Naples experience. J Exp Clin Cancer Res. 2013; 32(1): 14.
15- Igwa E, Azman AZF, Nardin AJ, Mohtarrudin N. ASSOCIATION BETWEEN HOMA-IR AND CANCER. International J Public Health and Clin Sciences. 2015;2 (2): 21
16- Sadighi S, Zokaasadi M, Kasaeian A, maghsudi S, Kamranzadeh . The effect of immunohistochemically detected p53 accumulation in prognosis of breast cancer; A retrospective survey of outcome. PloS one, 2017 ;12(8): e0182444.
| Files | ||
| Issue | Vol 11 No 4 (2019) | |
| Section | Original Articles | |
| DOI | https://doi.org/10.18502/bccr.v11i4.5725 | |
| Keywords | ||
| Metformin Tumor Cell Proliferation Breast Neoplasms | ||
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How to Cite
1.
Sadighi S, Saberian M, Behrouzi B, Najafi M, Jahanzad I, Omranipour R. Metformin Efficacy on Proliferation Indices of Tumoral Cells in Non-Diabetic Patients with Invasive Breast Cancer Referring to the Cancer Institute of Iran. Basic Clin Cancer Res. 2020;11(4):166-172.
