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Published Online:https://doi.org/10.2217/fon.10.87

Comparing the experience accumulated for more than 40 years in the Laboratory of Endocrinology of Petrov Institute of Oncology (St Petersburg, Russia) with similar approaches practiced elsewhere, evidence supports the reasonability of metabolic rehabilitation of patients suffering from breast cancer or other hormone-dependent malignancies. The primary objective of such approaches is to improve treatment results by ameliorating hormonal–metabolic disturbances, including excess body fat, glucose intolerance, insulin resistance and manifestations of endocrine–genotoxic switchings, and modify tissue and cellular targets or mechanisms related or nondirectly related to the aforementioned disturbances. The relevant measures may be categorized as pharmacological (antidiabetic biguanides exemplified with metformin being most popular but not exclusive) and nonpharmacological (rational nutrition, moderate physical activity and so forth) and used separately or in different combinations.

Papers of special note have been highlighted as: ▪ of interest ▪▪ of considerable interest

Bibliography

  • Dilman VM: Metabolic immunodepression which increases the risk of cancer. Lancet2(8050),1207–1209 (1977).▪▪ Important paper that describes mechanisms of associations between cancer risk and hormonal-metabolic disturbances and the need of the latter elimination.
  • Breslow L, Agran L, Breslow DM, Morganstern M, Ellwein L: Cancer control: implications from its history. J. Natl Cancer Inst.59(2 Suppl.),671–686 (1977).
  • Lowe J: The Metabolic Treatment of Fibromyalgia. McDowell Publishing, Lafayette, CO, USA, 312 (2000).
  • Dilman VM: Endocrinological Oncology. Meditsina, Leningrad, Russia (1983).
  • Dilman VM, Berstein LM, Tsyrlina EV et al.: On correction of hormonal-metabolic disturbances in oncological patients. Effect of biguanides (phenformin and adebit), misclerone and diphenin. Vopr. Onkol.21(11),33–39 (1975).▪ First paper on metabolic rehabilitation of oncological patients presenting own data.
  • Dilman VM, Ryabov SI, Tsyrlina EV et al.: Reduction of body weight, cholesterol and glucose level under influence of metformin in patients with cancer and atherosclerosis. Vopr. Onkol.18(2),84–86 (1972).
  • Dilman VM: Aging, Climax and Cancer. Meditsina, Leningrad, Russia (1968).
  • Dilman VM, Berstein LM, Ostroumova MN et al.: Metabolic immunodepression and metabolic immunotherapy. An attempt of improvement in immunologic response in breast cancer patients by correction of metabolic disturbances. Oncology39,13–19 (1982).▪ Important paper that describes mechanisms of associations between cancer risk and hormonal-metabolic disturbances and the need of the latter elimination.
  • Dilman VM, Berstein LM, Yevtushenko TP et al.: Preliminary evidence on metabolic rehabilitation of cancer patients. Arch. Geschwulstf58,175–183 (1988).▪ The summary of metabolic rehabilitation results by the time of publication.
  • 10  Dilman V, Dean W: The Neuroendocrine Theory of Aging and Degenerative Disease. The Center for Bio-Gerontology, Pensacola, FL, USA (1992).
  • 11  Berstein LM, Yevtushenko TP, Tsyrlina EV et al.: Comparative study of 5- and 10-years results of metabolic rehabilitation of oncological patients. In: Neuroendocrine System, Metabolism, Immunity and Cancer. Hanson KP, Dilman VM (Eds). NN Petrov Research Institute of Oncology Publ, St Petersburg, Russia, 102–112 (1992).
  • 12  Berstein LM, Santen RJ (Eds): Innovative Endocrinology of Cancer. Landes Bioscience, Springer Science+Business Media, TX, USA (2008).
  • 13  MacMahon B: Overview of studies on endometrial cancer and other types of cancer in humans: perspectives of an epidemiologist. Semin. Oncol.24(1 Suppl. 1),S1–S39 (1997).
  • 14  Berstein LM: Oncoendocrinology: Traditions, contemporary situation and perspectives. Nauka Publishers, St Petersburg, Russia (2004).
  • 15  Barnadas A, Gil M, Sanchez-Rovira P: Neoadjuvant endocrine therapy for breast cancer: past, present and future. Anti-Cancer Drugs19,339–347 (2009).
  • 16  Miller WR: Clinical, pathological, proliferative and molecular responses associated with neoadjuvant aromatase inhibitor treatment in breast cancer. J. Steroid Biochem. Mol. Biol.118(4–5),273–276 (2010).
  • 17  Semiglazov VF, Semiglazov VV, Dashyan GA et al.: Phase 2 randomized trial of primary endocrine therapy versus chemotherapy in postmenopausal patients with estrogen receptor-positive breast cancer. Cancer110(2),244–254 (2007)
  • 18  Bokhman JV, Chepick OF, Volkova AT, Vishnevsky AS: Can primary endometrial carcinoma stage I be cured without surgery and radiation therapy? Gynecol. Oncol.20(2),139–155 (1985).
  • 19  Yamazawa K, Hirai M, Fujito A: Fertility-preserving treatment with progestin, and pathological criteria to predict responses, in young women with endometrial cancer. Hum. Reprod.22(7),1953–1958 (2007).
  • 20  Blagosklonny MV: Prevention of cancer by inhibiting aging. Cancer Biol. Ther.7,1520–1524 (2008).▪ Demonstrates approaches that address systemic and cellular targets.
  • 21  Berstein LM: Clinical usage of hypolipidemic and antidiabetic drugs in the prevention and treatment of cancer. Cancer Lett.224(2),203–212 (2005).▪ Overview of existing and own data by the publication time.
  • 22  Liao JK: Clinical implications for statin pleiotropy. Curr. Opin. Lipidol.16(6),624–629 (2005).
  • 23  Zhou G, Myers R, Li Y et al.: Role of AMP-activated protein kinase in mechanism of metformin action. J. Clin. Invest.108(8),1167–1174 (2001).
  • 24  Rose DP, Vona-Davis L: Influence of obesity on breast cancer receptor status and prognosis. Expert Rev. Anticancer Ther.9(8),1091–1101 (2009).
  • 25  Ruhstaller T, von Moos R, Rufibach K et al.: Breast cancer patients on endocrine therapy reveal more symptoms when self-reporting than in pivotal trials: an outcome research study. Oncology76,142–148 (2009).
  • 26  Yue W, Fan P, Wang J, Li Y, Santen RJ: Mechanisms of acquired resistance to endocrine therapy in hormone-dependent breast cancer cells. J. Steroid Biochem. Mol. Biol.106,102–110 (2007).
  • 27  Musgrove EA, Sutherland RL: Biological determinants of endocrine resistance in breast cancer. Nat. Rev. Cancer9,631–643 (2009).
  • 28  Saylor PJ, Smith MR: Metabolic complications of androgen deprivation therapy for prostate cancer. J. Urol.181,1998–2008 (2009).▪ Interesting summary devoted to an important problem.
  • 29  Heideman WH, Russell NS, Gundy C, Rookus MA, Voskuil DW: The frequency, magnitude and timing of post-diagnosis body weight gain in Dutch breast cancer survivors. Eur. J. Cancer45,119–126 (2009).
  • 30  McCourt CK, Mutch DG, Gibb RK et al.: Body mass index: relationship to clinical, pathologic characteristics and features of microsatellite instability in endometrial cancer. Gynecol. Oncol.104,535–539 (2007).▪ Important study connecting DNA repair defects with hormonal-metabolic disturbances in cancer patients.
  • 31  Golubev AG: The other side of metabolism. Biokhimiia (Moscow)61(11),2018–2039 (1996).
  • 32  Unoki H, Yamagishi S: Advanced glycation end products and insulin resistance. Curr. Pharm. Des.14(10),987–989 (2008).
  • 33  van Kruijsdijk RC, van der Wall E, Visseren FL: Obesity and cancer: the role of dysfunctional adipose tissue. Cancer Epidemiol. Biomarkers Prev.18(10),2569–2578 (2009).
  • 34  Warburg O: On the origin of cancer cells: 30 years of research. Science123,309–314 (1956).
  • 35  Shaw RJ: Glucose metabolism and cancer. Curr. Opin. Cell Biol.18,598–608 (2006).▪▪ Excellent review on multifaceted associations between glucose and cancer.
  • 36  DeBerardinis RJ, Lum JJ, Hatzivassiliou G, Thompson CB: The biology of cancer: metabolic reprogramming fuels cell growth and proliferation. Cell. Metab.7(1),11–20 (2008).
  • 37  Gogvadze V, Orrenius S, Zhivotovsky B: Mitochondria in cancer cells: what is so special about them. Trends Cell. Biol.18,165–173 (2008).
  • 38  Shackelford DB, Shaw RJ: The LKB1–AMPK pathway: metabolism and growth control in tumour suppression. Nat. Rev. Cancer9(8),563–575 (2009).▪▪ Excellent overview of connection in LKB1–adenosine monophosphate-activated protein kinase (AMPK) tandem with an analysis of the data on AMPK activators including metformin.
  • 39  Hirsch HA, Iliopoulos D, Tsichlis PN, Struhl K: Metformin selectively targets cancer stem cells, and acts together with chemotherapy to block tumor growth and prolong remission. Cancer Res.69,7507–7511 (2009).
  • 40  Stearns V, Rae JM: Pharmacogenetics and breast cancer endocrine therapy: CYP2D6 as a predictive factor for tamoxifen metabolism and drug response? Expert Rev. Mol. Med.10,E34 (2008).
  • 41  Aquilante CL: Pharmacogenetics of thiazolidinedione therapy. Pharmacogenomics8(8),917–931 (2007).▪ Comprehensive example of this area of importance.
  • 42  Reitman ML, Schadt EE: Pharmacogenetics of metformin response: a step in the path toward personalized medicine. J. Clin. Invest.117(5),1226–1229 (2007).▪ Another example of this area of importance.
  • 43  Berstein LM: Role of endocrine-genotoxic switchings in cancer and other human diseases: basic triad. Adv. Exp. Med. Biol.630,35–51 (2008).
  • 44  Bershtein LM, Tsyrlina EV, Kovalevskii AI et al.: Endocrine-genotoxic switchings as promoter of main noninfectious diseases. Vestn. Ross. Akad. Med. Nauk.1,12–18 (2008) [in Russian].
  • 45  Berstein LM: Endocrinology of the wild and mutant BRCA1 gene and types of hormonal carcinogenesis. Future Oncol.4(1),23–39 (2008).
  • 46  Eliassen AH, Hankinson SE: Endogenous hormone levels and risk of breast, endometrial and ovarian cancers: prospective studies. Adv. Exp. Med. Biol.630,148–165 (2008).
  • 47  Neilson HK, Friedenreich CM, Brockton NT, Millikan RC: Physical activity and postmenopausal breast cancer: proposed biologic mechanisms and areas for future research. Cancer Epidemiol. Biomarkers Prev.18(1),11–27 (2009).
  • 48  Pollak M: Insulin and insulin-like growth factor signalling in neoplasia. Nat. Rev. Cancer8,915–928 (2008).
  • 49  Sjöström L, Gummesson A, Sjöström CD et al.: Effects of bariatric surgery on cancer incidence in obese patients in Sweden (Swedish Obese Subjects Study): a prospective, controlled intervention trial. Lancet Oncol.10,653–662 (2009).▪▪ Milestone paper on effect of bariatric surgery as a preventive measure.
  • 50  Vigersky RA, Filmore-Nassar A, Glass AR: Thyrotropin suppression by metformin. J. Clin. Endocrinol. Metab.91,225–227 (2006).
  • 51  Goodwin PJ, Pritchard KI, Ennis M, Clemons M, Graham M, Fantus IG: Insulin-lowering effects of metformin in women with early breast cancer. Clin. Breast Cancer8,501–505 (2008).▪ Interesting paper of the experienced expert in metformin and cancer area.
  • 52  Demark-Wahnefried W, Rock CL, Patrick K, Byers T: Lifestyle interventions to reduce cancer risk and improve outcomes. Am. Fam. Physician77(11),1573–1578 (2008).
  • 53  Pan SY, DesMeules M: Energy intake, physical activity, energy balance, and cancer: epidemiologic evidence. Methods Mol. Biol.472,191–215 (2009).
  • 54  Yeh HC, Duncan BB, Schmidt MI, Wang NY, Brancati FL: Diabetes and quitting of smoking. Ann. Intern. Med.152,10–17 (2010).
  • 55  Patterson RE, Cadmus LA, Emond JA, Pierce JP: Physical activity, diet, adiposity and female breast cancer prognosis: a review of the epidemiologic literature. Maturitas66(1),5–15 (2010).
  • 56  Bernstein L: Identifying population-based approaches to lower breast cancer risk. Oncogene27(Suppl. 2),S3–S8 (2008).▪▪ Paper of notable importance summarizing author’s experience and views on the role of physical activity and other healthy lifestyle approaches.
  • 57  Schernthaner G: Pleiotropic effects of thiazolidinediones on traditional and non-traditional atherosclerotic risk factors. Int. J. Clin. Pract.63,912–929 (2009).
  • 58  Mann D, Reynolds K, Smith D, Muntner P: Trends in statin use and low-density lipoprotein cholesterol levels among US Adults: impact of the 2001 National Cholesterol Education Program guidelines. Ann. Pharmacother.42(9),1208–1215 (2008).
  • 59  Alimova IN, Liu B, Fan Z et al.: Metformin inhibits breast cancer cell growth, colony formation and induces cell cycle arrest in vitro. Cell Cycle8,909–915 (2009).
  • 60  Anisimov VN, Berstein LM, Egormin PA et al.: Effect of metformin on life span and on the development of spontaneous mammary tumors in HER-2/neu transgenic mice. Exp. Gerontol.40,685–693 (2005).
  • 61  Campbell MJ, Esserman LJ, Zhou Y et al.: Breast cancer growth prevention by statins. Cancer Res.66,8707–8714 (2006).
  • 62  Dowling RJ, Zakikhani M, Fantus IG, Pollak M, Sonenberg N: Metformin inhibits mammalian target of rapamycin-dependent translation initiation in breast cancer cells. Cancer Res.67,10804–10812 (2007).
  • 63  Chong CR, Chabner BA: Mysterious metformin. Oncologist14,1178–1181 (2009).▪ Important paper underlining positive effects of metformin and the need of resurrecting of phenformin.
  • 64  Huang X, Wullschleger S, Shpiro N et al.: Important role of the LKB1–AMPK pathway in suppressing tumorigenesis in PTEN-deficient mice. Biochem. J.412(2),211–221 (2008).
  • 65  Zhou Z, Rahme E, Pilote L: Are statins created equal? Evidence from randomized trials of pravastatin, simvastatin, and atorvastatin for cardiovascular disease prevention. Am. Heart J.151,273–281 (2006).
  • 66  Kuoppala J, Lamminpää A, Pukkala E: Statins and cancer: a systematic review and meta-analysis. Eur. J. Cancer44,2122–2132 (2008).▪ Paper of importance accentuating complexity of the problem.
  • 67  Garwood ER, Kumar AS, Baehner FL et al.: Fluvastatin reduces proliferation and increases apoptosis in women with high grade breast cancer. Breast Cancer Res. Treat.119,137–144 (2010).
  • 68  Yu HN, Noh EM, Lee YR et al.: Troglitazone enhances tamoxifen-induced growth inhibitory activity of MCF-7 cells. Biochem. Biophys. Res. Commun.377,242–247 (2008).
  • 69  Ramos-Nino ME, MacLean CD, Littenberg B: Association between cancer prevalence and use of thiazolidinediones: results from the Vermont Diabetes Information System. BMC Med.5,17 (2007).
  • 70  Rodríguez-Enríquez S, Marín-Hernández A, Gallardo-Pérez JC, Carreño-Fuentes L, Moreno-Sánchez R: Targeting of cancer energy metabolism. Mol. Nutr. Food Res.53,29–48 (2009).
  • 71  Menendez JA, Vellon L, Lupu R: The antiobesity drug Orlistat induces cytotoxic effects, suppresses Her-2/neu (erbB-2) oncogene overexpression, and synergistically interacts with trastuzumab (Herceptin) in chemoresistant ovarian cancer cells. Int. J. Gynecol. Cancer16,219–221 (2006).
  • 72  Chow LW, Loo WT, Toi M: Current directions for COX-2 inhibition in breast cancer. Biomed. Pharmacother.59(Suppl. 2),S281–S284 (2005).
  • 73  Zhang MZ, Xu J, Yao B et al.: Inhibition of 11b-hydroxysteroid dehydrogenase type II selectively blocks the tumor COX-2 pathway and suppresses colon carcinogenesis in mice and humans. J. Clin. Invest.119(4),876–885 (2009).
  • 74  Gibbons JJ, Abraham RT, Yu K: Mammalian target of rapamycin: discovery of rapamycin reveals a signaling pathway important for normal and cancer cell growth. Semin. Oncol.36(Suppl. 3),S3–S17 (2009).
  • 75  Athar M, Back JH, Tang X et al.: Resveratrol: a review of preclinical studies for human cancer prevention. Toxicol. Appl. Pharmacol.224,274–283 (2007).
  • 76  Saiah E: The role of 11β-hydroxysteroid dehydrogenase in metabolic disease and therapeutic potential of 11 β-HSD1 inhibitors. Curr. Med. Chem.15,642–649 (2008).
  • 77  Macciò A, Madeddu C, Mantovani G: Adipose tissue as target organ in the treatment of hormone-dependent breast cancer: new therapeutic perspectives. Obes. Rev.10,660–670 (2009).▪ Comprehensive paper important for metabolic rehabilitation problem.
  • 78  Bozzetti F, Mori V: Nutritional support and tumour growth in humans: a narrative review of the literature. Clin. Nutr.28,226–230 (2009).
  • 79  Chlebowski RT, Blackburn GL, Thomson CA et al.: Dietary fat reduction and breast cancer outcome: interim efficacy results from the Women’s Intervention Nutrition Study. J. Natl Cancer Inst.98,1767–1776 (2006).▪ Paper of notable importance summarizing author’s experience.
  • 80  Thomson CA, Thompson PA: Dietary patterns, risk and prognosis of breast cancer. Future Oncol.5,1257–1269 (2009).
  • 81  Chan AT, Giovannucci EL: Primary prevention of colorectal cancer. Gastroenterology138(6),2029–2043.E10 (2010).
  • 82  Thompson PA, Gerner EW: Current concepts in colorectal cancer prevention. Expert Rev. Gastroenterol. Hepatol.3(4),369–382 (2009).
  • 83  Atiomo W, Read A, Golding M et al.: Local recruitment experience in a study comparing the effectiveness of a low glycaemic index diet with a low calorie healthy eating at achieving weight loss and reducing the risk of endometrial cancer in women with polycystic ovary syndrome. Contemp. Clin. Trials30,451–456 (2009).
  • 84  Oliveria SA, Koro CE, Yood MU, Sowell M: Cancer incidence among patients treated with antidiabetic pharmacotherapy. Diabetes Metabol. Syndrome Clin. Res. Rev.2,47–57 (2008).
  • 85  Garwood ER, Kumar AS, Baehner FL et al.: Fluvastatin reduces proliferation and increases apoptosis in women with high grade breast cancer. Breast Cancer Res. Treat.119,137–144 (2010).
  • 86  Bowker SL, Majumdar SR, Veugelers P, Johnson JA: Increased cancer-related mortality for patients with Type 2 diabetes who use sulfonylureas or insulin. Diabetes Care29,254–258 (2006).
  • 87  Currie CJ, Poole CD, Gale EA: The influence of glucose-lowering therapies on cancer risk in Type 2 diabetes. Diabetologia52,1766–1777 (2009).▪▪ Excellent analysis of recently published data.
  • 88  Libby G, Donnelly LA, Donnan PT, Alessi DR, Morris AD, Evans JM: New users of metformin are at low risk of incident cancer: a cohort study among people with Type 2 diabetes. Diabetes Care32,620–625 (2009).
  • 89  Vazquez-Martin A, Oliveras-Ferraros C, Del Barco S, Martin-Castillo B, Menendez JA: If mammalian target of metformin indirectly is mammalian target of rapamycin, then the insulin-like growth factor-1 receptor axis will audit the efficacy of metformin in cancer clinical trials. J. Clin. Oncol.27,E207–E209 (2009).
  • 90  Berstein LM: Metformin, insulin, breast cancer and more… Future Oncol.5,309–312 (2009).
  • 91  Berstein LM, Kvatchevskaya JO, Poroshina TE et al.: Insulin resistance, its consequences for the clinical course of the disease, and possibilities of correction in endometrial cancer. J. Cancer Res. Clin. Oncol.130,687–693 (2004).
  • 92  Ooi M, Kotoula V, Charalambous E: The antidiabetic biguanide metformin induces growth arrest in thyroid carcinoma cells in vitro. Presented at: Proc. 91th Annual Endocrine Soc. (USA)P2.521 (2009).
  • 93  Cantrell LA, Zhou C, Mendivil A, Malloy KM, Gehrig PA, Bae-Jump V: Metformin is a potent inhibitor of endometrial cancer cell proliferation – implications for a novel treatment strategy. Gynecol. Oncol.116,92–98 (2010).
  • 101  Clinical trials.gov: metformin, glitazones and cancer www.ClinicalTrials.gov (Accessed 21 January 2010)▪ Important site presenting information on clinical trials recently started with mentioned compounds.
  • 102  Lloyd RS: DNA repair deficiency associated with obesity and the metabolic syndrome Report on NIH (USA) grant 1R01DK075974–01A2, 2009–2014 www.researchprofiles.collexis.com/ohsuv3/grantDetail (Accessed 14 January 2010)