Metformin in neoadjuvant systemic therapy of breast cancer patients with metabolic syndrome

  • Roman Liubota National Medical University named after O.O Bogomolets
  • Valeriy Cheshuk National Medical University named after O.O. Bogomolets
  • Olexyy Zotov National Medical University named after O.O. Bogomolets
  • Roman Vereshchako National Medical University named after O.O. Bogomolets
  • Mykola Anikusko Kyiv Municipal City Clinical Oncological Centre
  • Iryna Liubota Kyiv Municipal City Clinical Oncological Centre
  • Vitaliy Gur'yanov National Medical University named after O.O. Bogomolets
Keywords: breast cancer, metabolic syndrome, neoadjuvant systemic therapy, metformin,

Abstract


Background

The aim of this prospective randomized trial was to investigate the influence of metformin on the effectiveness of neoadjuvant systemic therapy in breast cancer patients with metabolic syndrome.

Patients and methods

The study included 72 patients (from 31 to 77 years of age) who received neoadjuvant systemic treatment for stage II-III breast cancer at the National Medical University named after O.O Bogomolets, Municipal City Clinical Oncological Center, Department of Oncology, Kyiv during 2010 - 2014. Metabolic syndrome was diagnosed in all patients according to the International Diabetes Federation criteria. They were divided in two groups: group 1 that included 36 patients with metabolic syndrome and breast cancer who did not intake metformin during neoadjuvant systemic therapy, and group 2 that included 36 patients with metabolic syndrome and breast cancer who received metformin with neoadjuvant systemic therapy.

Results

Complete clinical response was identified in 2 (6 %) patients from group 1 and 10 (27.5 %) patients from group 2. Overall clinical response rate (cCR + cPR) was achieved in 28 (77.5 %) patients treated with metformin compared to 9 (25 %) patients from group 1. A stable disease was observed in 19 (53 %) patients who were not taking metformin. The rate of pathological complete response was 26.5 % (9 patients) in the metformin group and 6 % (2 patients) in the non-metformin group.

Conclusions

Combined neoadjuvant systemic anticancer therapy of breast cancer patient with metabolic syndrome with metformin has a higher clinical and pathological overall response rate than treatment without metformin.

References

Ferlay J, Soerjomataram I, Ervik M, Dikshit R, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2015 Mar; 136(5):E359-86. doi: 10.1002/ijc.29210.

Bulletin of National cancer registry of Ukraine № 9 - "Cancer in Ukraine, 2006-2007", Kyiv – 2008.

Bulletin of National cancer registry of Ukraine № 15 - " Cancer in Ukraine, 2012-2013", Kyiv – 2014.

The IDF consensus worldwide definition of the metabolic syndrome // International Diabetes Federation, 2006. www.idf.org/metabolic_syndrome, website of the International Diabetes Federation

Esposito K, Chiodini P, Colao A, et al. Metabolic Syndrome and Risk of Cancer: A systematic review and meta-analysis. Diabetes Care. 2012 Nov; 35(11):2402–2411. doi: 10.2337/dc12-0336.

Esposito K, Chiodini P, Capuano A, et al. Metabolic syndrome and postmenopausal breast cancer: systematic review and meta-analysis. Menopause. 2013 Dec; 20(12):1301-1309. doi: 10.1097/GME.0b013e31828ce95d.

Stebbing J, Sharma A, North B, et al. A metabolic phenotyping approach to understanding relationships between metabolic syndrome and breast tumour responses to chemotherapy. Ann Oncol. 2012 Apr; 23(4):860-866. doi: 10.1093/annonc/mdr347.

Liubota R, Zotov A, Vereshchako R, et al. Metformin in neoadjuvant systemic treatment in breast cancer patients with metabolic syndrome. Ann Oncol. 2016 Oct; 27(Supplement 6): vi95. doi: 10.1093/annonc/mdw365.81

Xu B, Lovre D, Mauvais-Jarvis F. The effect of selective estrogen receptor modulators on type 2 diabetes onset in women: Basic and clinical insights. J Diabetes Complications. 2017 Apr; 31(4):773–779. doi: 10.1016/j.jdiacomp.2016.12.010

Lipscombe LL, Fischer HD, Yun L, et al. Association between tamoxifen treatment and diabetes: a population-based study. Cancer. 2012May; 118(10):2615-2622. doi: 10.1002/cncr.26559

Campbell JM, Bellman SM, Stephenson MD. Metformin reduces all-cause mortality and diseases of ageing independent of its effect on diabetes control: A systematic review and meta-analysis. Ageing Res Rev. 2017 Nov; 40:31-44. doi: 10.1016/j.arr.2017.08.003

Kahn BB, Alquier T, Carling D, Hardie DG. AMP-activated protein kinase: Ancient energy gauge provides clues to modern understanding of metabolism. Cell Metabolism. 2005 Jan;1(1): 15-25. doi: 10.1016/j.cmet.2004.12.003

Shchepotin IB, Zotov AS, Liubota RV, et al. Role of ovarian suppression in the combined treatment of breast cancer patients in premenopause. Vopr Onkol. 2013; 59(3):397-404. PMID: 23909046

Eisenhauer EA, Therasse P, Bogaerts J, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009 Jan; 45: 228–247. doi: 10.1016/j.ejca.2008.10.026

Ogston KN, Miller ID, Payne S, et al. A new histologic grading system to assess response of breast cancers to primary chemotherapy: prognostic significance and survival. Breast. 2003 Oct;12: 320-327. PMID: 14659147

Senkus E, Kyriakides S, Penault-Llorca F, Poortmans P, Thompson A, Zackrisson S, Cardoso F, on behalf of the ESMO Guidelines Working Group. Primary breast cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 24 (Supplement 6): vi7–vi23, 2013 Sep. doi:10.1093/annonc/mdt284

Shchepotin IB, Zotov AS, Liubota RV, et al. The basic mechanisms the influence of metabolic syndrome on the risk and prognosis of breast cancer (review). Tumors of female reproductive system. 2013 Jun; 1-2: 45-51. doi: 10.17650/1994-4098-2013-0-1-2-45-51

Published
2018/07/23
Section
Original Scientific Paper