Metformin increases mammographic breast density: a randomized controlled trial
-
Sadaf Alipour
,
Ladan Hosseini
,
Zohreh Forootan
,
Hadith Rastad
,
Leila Bayani
,
Mahboubeh Abedi
,
Bita Eslami
Abstract
Background Mammographic breast density (MBD) is directly related to the risk of breast cancer. In vivo and in vitro studies have shown that metformin can reduce the proliferation and growth of breast cancer tissue. The aim of this study was to determine the effect of metformin on MBD in non-diabetic premenopausal women. Methods A double-blind, placebo-controlled study was performed. A total of 151 premenopausal women received 500 mg metformin tablets twice a day for 6 months, or a placebo, were included. The changes in MBD were compared between the two groups. Results Final data were evaluated based on 67 and 84 women in the metformin and placebo groups, respectively. Based on results from Ordinal Logistic Regression, the odds of achieving a higher density for the intervention group was approximately 2.33 (95% CI, 1.04 to 5.18) times that of the placebo group. Conclusions This clinical trial showed that consumption of metformin 500 mg twice daily for 6 months is associated with a higher mammographic breast density as compared to the placebo group. As metformin is used very commonly, we suggest that this medicine should be considered as a probable confounding factor when conducting studies about MBD.
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16. Kim J, Lim W, Kim EK, Kim MK, Paik NS, Jeong SS, Yoon JH, Park CH, Ahn SH, Kim LS, Han S. Phase II randomized trial of neoadjuvant metformin plus letrozole versus placebo plus letrozole for estrogen receptor positive postmenopausal breast cancer (METEOR). BMC cancer. 2014;14(1):1-5.
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18. Tapia E, Villa-Guillen DE, Chalasani P, Centuori S, Roe DJ, Guillen-Rodriguez J, Huang C, Galons JP, Thomson CA, Altbach M, Trujillo J. A randomized controlled trial of metformin in women with components of metabolic syndrome: intervention feasibility and effects on adiposity and breast density. Breast Cancer Research and Treatment. 2021;190(1):69-78.
19. Oskar S, Engmann NJ, Azus AR, Tehranifar P. Gestational diabetes, type II diabetes, and mammographic breast density in a US racially diverse population screened for breast cancer. Cancer Causes & Control. 2018;29:731-6.
20. Ozturk MA, Ozturk S, Eryilmaz M, Cinar S, Sertbas M, Ak F, Sertbas Y, Ozdemir A. Does metformin affect mammographic breast density in postmenopausal women with type 2 diabetes. Gynecological Endocrinology. 2020;36(9):800-2.
21. Eslami B, Omranipour R, Arian A, Bayani L, Abedi M, Alipour S. The association of metformin and aspirin intake with mammographic breast density: A cross-sectional study. Caspian Journal of Internal Medicine. 2023;14(4):741.
22. Zafar S. Role of metformin in correcting hyperinsulinemia, menstrual irregularity and anovulation in polycystic ovary syndrome. Journal of Ayub Medical College Abbottabad. 2005;17(4).
23. Sharma N, Lugani Y, Kaur A, Ahuja VK. Effect of metformin on insulin levels, blood sugar, and body mass index in polycystic ovarian syndrome cases. Journal of family medicine and primary care. 2019;8(8):2691.
24. Stumvoll M, Nurjhan N, Perriello G, Dailey G, Gerich JE. Metabolic effects of metformin in non-insulin-dependent diabetes mellitus. New England Journal of Medicine. 1995;333(9):550-4.
25. Sadeghi A, Mousavi SM, Mokhtari T, Parohan M, Milajerdi A. Metformin therapy reduces obesity indices in children and adolescents: a systematic review and meta-analysis of randomized clinical trials. Childhood Obesity. 2020;16(3):174-91.
26. DeFronzo R, Fleming GA, Chen K, Bicsak TA. Metformin-associated lactic acidosis: Current perspectives on causes and risk. Metabolism. 2016;65(2):20-9.
27. Shurrab NT, Arafa ES. Metformin: A review of its therapeutic efficacy and adverse effects. Obesity medicine. 2020;17:100186.
28. Moini A, Salari E, Rashidi H, Maajani K, Abedi M, Bayani L, Alipour S. Evaluation of the association of endometriosis and mammographic breast density, a cross-sectional study. BMC Women's Health. 2022;22(1):81.
29. Eslami B, Alipour S, Omranipour R, Aryan A, Bayani L, Abedi M. Cosmetics Use and Mammographic Breast Density (MBD) in Iranian Women: A Cross-Sectional Study. Current Women's Health Reviews. 2024;20(1):52-61.
2. Shawky MS, Martin H, Hugo HJ, Lloyd T, Britt KL, Redfern A, Thompson EW. Mammographic density: a potential monitoring biomarker for adjuvant and preventative breast cancer endocrine therapies. Oncotarget. 2017;8(3):5578.
3. Cuzick J, Warwick J, Pinney E, Duffy SW, Cawthorn S, Howell A, Forbes JF, Warren RM. Tamoxifen-induced reduction in mammographic density and breast cancer risk reduction: a nested case–control study. Journal of the National Cancer Institute. 2011;103(9):744-52.
4. Samuel SM, Varghese E, Kubatka P, Triggle CR, Büsselberg D. Metformin: the answer to cancer in a flower? Current knowledge and future prospects of metformin as an anti-cancer agent in breast cancer. Biomolecules. 2019;9(12):846.
5. Lee Argov EJ, Acheampong T, Terry MB, Rodriguez CB, Agovino M, Wei Y, Athilat S, Tehranifar P. Independent and joint cross-sectional associations of statin and metformin use with mammographic breast density. Breast Cancer Research. 2020;22:1-9.
6. Chen K, Li Y, Guo Z, Zeng Y, Zhang W, Wang H. Metformin: Current clinical applications in nondiabetic patients with cancer. Aging (Albany NY). 2020;12(4):3993.
7. Saraei P, Asadi I, Kakar MA, Moradi-Kor N. The beneficial effects of metformin on cancer prevention and therapy: a comprehensive review of recent advances. Cancer management and research. 2019:3295-313.
8. Heckman-Stoddard BM, Gandini S, Puntoni M, Dunn BK, DeCensi A, Szabo E. Repurposing old drugs to chemoprevention: the case of metformin. In: Seminars in oncology. WB Saunders. 2016; 43(1):123-133.
9. Froissart M, Rossert J, Jacquot C, Paillard M, Houillier P. Predictive performance of the modification of diet in renal disease and Cockcroft-Gault equations for estimating renal function. Journal of the American Society of Nephrology. 2005;16(3):763-3.
10. Bershtein LM, Vasil'ev DA, Kovalenko IG, Poroshina TE, Kisel'nikov KS, Boiarkina MP, Zaĭtsev AN. The influence of metformin and N-acetylcysteine on mammographic density in postmenopausal women. Voprosy Onkologii. 2012;58(1):45-9.
11. Ahmadinejad N, Movahedinia S, Movahedinia S, Naieni KH, Nedjat S. Distribution of Breast Density in Iranian Women and its Association withBreast Cancer Risk Factors. Iranian Red Crescent Medical Journal. 2013; 15(12): e16615.
12. Zanello PA, Robim AF, Oliveira TM, Elias Junior J, Andrade JM, Monteiro CR, Sarmento Filho JM, Carrara HH, Muglia VF. Breast ultrasound diagnostic performance and outcomes for mass lesions using Breast Imaging Reporting and Data System category 0 mammogram. Clinics. 2011;66:443-8.
13. Boyd NF, Martin LJ, Yaffe MJ, Minkin S. Mammographic density and breast cancer risk: current understanding and future prospects. Breast cancer research. 2011;13:1-2.
14. Alipour S, Hosseini L, Bayani L, Saberi A, Alikhassi A. Association of reproductive and menstrual characteristics with mammographic density. Archives of Breast Cancer. 2014:20-4.
15. Buschard K, Thomassen K, Lynge E, Vejborg I, Tjønneland A, von Euler-Chelpin M, Andersen ZJ. Diabetes, diabetes treatment, and mammographic density in Danish Diet, Cancer, and Health cohort. Cancer Causes & Control. 2017;28:13-21.
16. Kim J, Lim W, Kim EK, Kim MK, Paik NS, Jeong SS, Yoon JH, Park CH, Ahn SH, Kim LS, Han S. Phase II randomized trial of neoadjuvant metformin plus letrozole versus placebo plus letrozole for estrogen receptor positive postmenopausal breast cancer (METEOR). BMC cancer. 2014;14(1):1-5.
17. Campagnoli C, Berrino F, Venturelli E, Abbà C, Biglia N, Brucato T, Cogliati P, Danese S, Donadio M, Zito G, Pasanisi P. Metformin decreases circulating androgen and estrogen levels in nondiabetic women with breast cancer. Clinical Breast Cancer. 2013;13(6):433-8.
18. Tapia E, Villa-Guillen DE, Chalasani P, Centuori S, Roe DJ, Guillen-Rodriguez J, Huang C, Galons JP, Thomson CA, Altbach M, Trujillo J. A randomized controlled trial of metformin in women with components of metabolic syndrome: intervention feasibility and effects on adiposity and breast density. Breast Cancer Research and Treatment. 2021;190(1):69-78.
19. Oskar S, Engmann NJ, Azus AR, Tehranifar P. Gestational diabetes, type II diabetes, and mammographic breast density in a US racially diverse population screened for breast cancer. Cancer Causes & Control. 2018;29:731-6.
20. Ozturk MA, Ozturk S, Eryilmaz M, Cinar S, Sertbas M, Ak F, Sertbas Y, Ozdemir A. Does metformin affect mammographic breast density in postmenopausal women with type 2 diabetes. Gynecological Endocrinology. 2020;36(9):800-2.
21. Eslami B, Omranipour R, Arian A, Bayani L, Abedi M, Alipour S. The association of metformin and aspirin intake with mammographic breast density: A cross-sectional study. Caspian Journal of Internal Medicine. 2023;14(4):741.
22. Zafar S. Role of metformin in correcting hyperinsulinemia, menstrual irregularity and anovulation in polycystic ovary syndrome. Journal of Ayub Medical College Abbottabad. 2005;17(4).
23. Sharma N, Lugani Y, Kaur A, Ahuja VK. Effect of metformin on insulin levels, blood sugar, and body mass index in polycystic ovarian syndrome cases. Journal of family medicine and primary care. 2019;8(8):2691.
24. Stumvoll M, Nurjhan N, Perriello G, Dailey G, Gerich JE. Metabolic effects of metformin in non-insulin-dependent diabetes mellitus. New England Journal of Medicine. 1995;333(9):550-4.
25. Sadeghi A, Mousavi SM, Mokhtari T, Parohan M, Milajerdi A. Metformin therapy reduces obesity indices in children and adolescents: a systematic review and meta-analysis of randomized clinical trials. Childhood Obesity. 2020;16(3):174-91.
26. DeFronzo R, Fleming GA, Chen K, Bicsak TA. Metformin-associated lactic acidosis: Current perspectives on causes and risk. Metabolism. 2016;65(2):20-9.
27. Shurrab NT, Arafa ES. Metformin: A review of its therapeutic efficacy and adverse effects. Obesity medicine. 2020;17:100186.
28. Moini A, Salari E, Rashidi H, Maajani K, Abedi M, Bayani L, Alipour S. Evaluation of the association of endometriosis and mammographic breast density, a cross-sectional study. BMC Women's Health. 2022;22(1):81.
29. Eslami B, Alipour S, Omranipour R, Aryan A, Bayani L, Abedi M. Cosmetics Use and Mammographic Breast Density (MBD) in Iranian Women: A Cross-Sectional Study. Current Women's Health Reviews. 2024;20(1):52-61.
| Files | ||
| Issue | Vol 15 No 4 (2023) | |
| Section | Original Articles | |
| Keywords | ||
| metformin breast density mammography confounding factor weight | ||
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How to Cite
1.
Alipour S, Hosseini L, Forootan Z, Rastad H, Bayani L, Abedi M, Eslami B. Metformin increases mammographic breast density: a randomized controlled trial. Basic Clin Cancer Res. 2025;15(4):237-244.
