Role of Estradiol, Progestins, Insulines and Adipocytokines in Breast Cancer Promotion in Post-Menopausal Women
Christian Jamin
AFACS 169 Bd Haussmann, Paris, France.
DOI: 10.4236/jct.2010.11007   PDF    HTML   XML   6,493 Downloads   10,722 Views   Citations


Estrogens and artificial progestins used in hormone replacement therapy increase breast cancer risk. This seems to bedue to a promoting and not initiating effect. A synergic effect of estradiol and hyperinsulinism has been shown. Insulinplays a role in the increase of breast cancer risk when associated with android obesity, sedentariness, type II diabetes,and high glycemic index food, alcohol and trans fatty acids intake. Natural menopause induces insulin resistance anddoes not induce a risk decrease. The role of insulin gives a new outlook on the influence of HRT in breast cancer promotion:estradiol alone, which improves insulin-sensitivity, does not increase breast cancer risk. Artificial progestinsassociated with estrogens increase the risk, whereas estrogens associated with progesterone do not. This could be dueto the fact that artificial progestins increase insulin resistance, whereas natural progesterone does not. Adipose tissue,which is an endocrine gland, is insulin dependant. Breast cancer and its seriousness are correlated to adipocytokincirculating levels such as resistin, leptin, interleukin 1, adipocyte fatty acid-binding protein, and are inversely correlatedto the level of adiponectin. Insulin could play a synergic role with sexual steroids by a direct effect and by increasingadipose tissue secretions.

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C. Jamin, "Role of Estradiol, Progestins, Insulines and Adipocytokines in Breast Cancer Promotion in Post-Menopausal Women," Journal of Cancer Therapy, Vol. 1 No. 1, 2010, pp. 43-47. doi: 10.4236/jct.2010.11007.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] R. T. Chlebowski., L. H. Kuller, R. L. Prentice, M. L. Stefanick, and E. Manson, “Breast cancer after use of estrogen plus progestin in post menopausal women,” New England Journal of Medicine, Vol. 360, pp. 573–587, 2009.
[2] P. M. Ravdin, K. A. Cronin, N. Howlader, C. D. Berg, and R. T. Chlebowski, “The decrease in breast-cancer incidence in 2003 in the United States,” New England Journal of Medicine, Vol. 356, pp. 1670–1674, 2007.
[3] Collaborative Group on Hormonal Factor in Breast Cancer, “Breast cancer and hormone replacement therapy: Collaborative reanalysis of data from 51 epidemiological studies of 52705 women with breast cancer and 108411 women without breast cancer,” Lancet, Vol. 350, pp. 1042–1059, 1997.
[4] J. E. Rossouw, G. L. Anderson, R. L. Prentice, A. Z. LaCroix, and C. Kooperberg, Writing group for the WHI “Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results,” From the Women's Health Initiative randomized controlled trial, Journal of the American Medical Association, Vol. 288, pp. 321–333, 2002.
[5] V. Beral, Million Women Study Collaborators, “Breast cancer and hormone-replacement therapy in the Million Women Study,” Lancet, Vol. 362, pp. 419–427, 2003.
[6] M. Ewertz, L. Mellemkjaer, H. Poulsen, S. Friis, and H. T. S?rensen, “Hormone use for menopausal symptoms and risk of breast cancer. A Danish cohort study,” British Journal of Cancer, Vol. 92, pp. 1293–1297, 2005.
[7] G. L. Anderson, M. Limacher, A. R. Assaf, T. Bassford, and S. A. Beresford, “Effects of conjugated equine estrogen in postmenopausal women with hysterectomy. The Women's Health Initiative randomized controlled trial,” Journal of the American Medical Association, Vol. 291, pp.1701–1712, 2004.
[8] W. Y. Chen, J. E. Manson, S. E. Hankinson, B. Rosner, and M. D. Holmes, “Unopposed estrogen therapy and the risk of invasive breast cancer,” Archives of Internal Medicine, Vol. 166, pp. 1027–1032, 2006.
[9] C. I. Li, K. E. Malone, P. L. Porter, N. S. Weiss, and M. T. Tang, “Relationship between long durations and different regimens of hormone therapy and risk of breast cancer,” Journal of the American Medical Association, Vol. 289, pp. 3254–3263, 2003.
[10] A. Fournier, F. Berrino, E. Riboli, V. Avenel, and F. Clavel-Chapelon, “Breast cancer risk in relation to types of hormone replacement therapy in the E3N-EPIC cohort,” International Journal of Cancer, Vol. 114, pp. 448–454, 2005.
[11] C. E. Wood, T. C. Register, C. J. Lees, H. Chen, and S. Kimrey, “Effects of estradiol with micronized progesterone or medroxyprogesterone acetate on risk markers for breast cancer in postmenopausal monkeys,” International Journal of Cancer, Vol. 101, pp. 125–134, 2007.
[12] S. Cummings, B. Ettinger, P. Delmas, P. Kenemans, and V. Stathopoulos, “The effects of Tibolone in older post-menopausal women,” New England Journal of Medicine, Vol. 359, pp. 697–708, 2008.
[13] W. Chen, D. Pettiti, and A. Geiger, “Mortality following development of breast cancer while using oestrogen or oestrogen plus progestin: A computer record-linkage study,” British Journal of Cancer, Vol. 93, pp. 392–398, 2005.
[14] A. Fournier, F. Berrino, and F. Clavel-Chapelon, “Unequal risks for breast cancer associated with different hormone replacement therapies: Results from the E3N cohort study,” British Journal of Cancer, Vol. 107, pp. 103–111, 2008.
[15] C. Schairer, M. Gail, C. Byrne, P. S. Rosenberg, and S. R. Sturgeon, “Estrogen replacement therapy and breast cancer survival in a large screening study,” Journal of the National Cancer Institute, Vol. 91, pp. 264–270, 1999.
[16] F. Schuetz, I. J. Diel, M. Pueschel, T. von Holst, and E. F. Solomayer, “Reduced incidence of distant metastases and lower mortality in 1072 patients with breast cancer with a history of hormone replacement therapy,” American Journal of Obstetrics and Gynecology, Vol. 196, pp. 342. e1-9, 2007.
[17] M. J. Gunter, D. R. Hoover, H. Yu, S. Wassertheil-Smoller, and T. E. Rohan, “Insulin, insulin-like growth factor-1, and risk of breast cancer in postmenopausal women,” Journal of the National Cancer Institute, Vol. 101, pp. 48–60, 2009.
[18] M. J. Borugian, S. B. Sheps, C. Kim-Sing, C. Van Patten, and J. D. Potter, “Insulin, macronutrient intake, and physical activity: are potential indicators of insulin resistance associated with mortality from breast cancer?” Cancer Epidemiol Biomarkers Prevention, Vol. 13, pp. 1163–1172, 2004.
[19] M. L. Garmendia, A. Pereira, M. E. Alvarado, and E. Atalah, “Relation between insulin resistance and breast cancer among chilean women,” Annals of Epidemiology, Vol. 17, pp. 403–409, 2007.
[20] R. Kaaks, E. Lundin, S. Rinaldi, J. Manjer, and C. Biessy, “Prospective study of IGF-I, IGF-binding proteins, and breast cancer risk, in northern and southern Sweden,” Cancer Causes Control, Vol. 13, pp. 307–316, 2002.
[21] P. J. Mink, E. Shahar, W. D. Rosamond, A. J. Alberg, and A. R. Folsom, “Serum insulin and glucose levels and breast cancer incidence,” American Journal of Epidemiology, Vol. 156, pp. 349–352, 2002.
[22] P. Goodwin, M. E. Ennis, K. Pritchard, M. Trudeau, and J. Koo, “Fasting insulin and out come in early-stage breast cancer: Results of a prospective cohort study,” Journal of Clinical Oncology, Vol. 20, pp. 42–51, 2001.
[23] M. N. Pollak, J. W. Chapman, L. Shepered, D. Meng, and P. Richardson, “Insuline resistance, estimed by serum C-peptide level, is associated with reduced event-free survival for post menopausal women in NCIC CGT MA.14 adjuvant-breast cancer trial,” Journal of Clinical Oncology, Vol. 24, pp. 524, 2006.
[24] D. Ish-Shalom, C. T. Christoffersen, P. Vorwerk, P., N. Sacerdoti-Sierra, and R. M. Shymko, “Mitogenic properties of insulin and insulin analogues mediated by the insulin receptor,” Diabetologia, Vol. 40, Supplement No. 2, pp. S25–31, 1997.
[25] L. Poretsky and M. F. Kalin, “The gonadotropic function of insulin,” Endocrine Reviews, Vol. 8, No. 132–141, 1987.
[26] S. M. Shafie and F. H. Grantham,“Role of hormones in the growth and regression of human breast cancer cells (MCF-7) transplanted into athymic nude mice,” Journal of the National Cancer Institute, Vol. 67, pp. 51–56, 1981.
[27] M. Pugeat, J. C. Crave, M. Elmidani, M. H. Nicolas, and M. Garoscio-Cholet, “Pathophysiology of sex hormone binding globulin (SHBG): Relation to insulin,” Journal of Steroid Biochemistry and Molecular Biology, Vol. 40, pp. 841–849, 1991.
[28] A. Belfiore, “The role of insulin receptor isoforms and hybrid insulin/IGF-1 receptors in human cancer,” Current Pharmaceutical Design, Vol. 13, pp. 671–686, 2007.
[29] J. Chappell, W. Leitner, S. Solomon, I. Golovchenko, and M. Goalstone, “Effect of insulin on cell cycle progression in MCF-7 breast cancer cells,” Journal of Biological Chemistry, Vol. 276, pp. 38023–38028, 2001.
[30] S. R. Lindheim, S. C. Presser, E. C. Ditkoff, M. A. Vijod, and F. Z. Stanczyk, “A possible bimodal effect of estrogen on insulin sensitivity in postmenopausal women and the attenuating effect of added progestin,” Fertil Steril, Vol. 60, pp. 664–667, 1993.
[31] G. K. Reeves, K. Pirie, V. Beral, J. Green, and E. Spencer, “Cancer incidence and mortality in relation to body mass index in the Million Women Study: Cohort study.” British Medical Journal, Vol. 335, pp. 1134, 2007.
[32] B. S. Connolly, C. Barnett, K. N. Vogt, J. Stone, and N. F. Boyd, “A meta analysis of published literature on waist-to-hip ratio and risk of breast cancer,” Nnutrition and Cancer, Vol. 44, pp. 127–138, 2002.
[33] N. Kumar, A. Cantor, K. Allen, and C. Cox, “Android obesity at diagnosis and breast cancer carcinoma survival,” Cancer, Vol. 88, pp. 2751–2757, 2000.
[34] P. Pasanisi, F. Berrino, M. de Petris, E. Venturelli, and A. Mastroianni, “Metabolic syndrome as a pronostic factor for breast cancer recurrences,” International Journal of Cancer, Vol. 119, pp. 236–238, 2006.
[35] B. A. Stoll, “Upper abdominal obesity, insulin resistance and breast cancer risk,” International Journal of Obesity and Related Metabolic Disorders, Vol. 26, pp. 747–753, 2002.
[36] A. S. Furberg, M. B. Veierod, T. Wilsgaard, L. Berstein, and I. Thune, “Serum high-density liporotein cholesterol, metabolic profile, and breast cancer risk,” Journal of the National Cancer Institute, Vol. 96, No. 15, pp. 1152–1160, 2004.
[37] M. D. Holmes, W. Y. Chen, D. Feskanich, C. H. Kroenke, and G. A. Colditz, “Physical activity and survival after breast cancer diagnosis,” Journal of the American Medical Association, Vol. 293, pp. 2479–2486, 2005.
[38] J. A. Ligibel, N. Campbell, A. Partridge, W. Y. Chen, and T. Salinardi, “Impact of a mixed strength and endurance exercise intervention on insulin levels in breast cancer survivors,” Journal of Clinical Oncology, Vol. 26, pp. 907–912, 2008.
[39] A. Pijpe, P. Manders, R. M. Brohet, J. M. Collée, and S. Verhoef, “Physical activity and the risk of breast cancer in BRCA 1-2 mutation carriers.” Breast Cancer Research, 2009.
[40] A. S. Fairey, K. S. Courneya, C. J. Field, G. J. Bell, L. W. Jones, and J. R. Mackey, “Effect of exercise training on fasting insulin, insulin resistance, insulin-like growth factors, and insulin like growth factor binding proteins in post menopausal breast cancer survivors: A randomised controlled trial,” Cancer Epidemiol Biomarkers and Prevention, Vol. 12, pp. 721–727, 2005.
[41] V. Chajès, A. C. Thiébaut, M. Rotival, E. Gauthier, and V. Maillard, “Association between serum trans-monoun-saturated fatty acids and breast cancer risk in the E3N-EPIC Study,” American Journal of Epidemiology, Vol. 167, pp. 1312–1320, 2008.
[42] U. Risérius, “Trans fatty acids and insulin resistance,” Atheroscler, Supplement Vol. 7, pp. 37–39, 2006.
[43] B. A. Stoll, “Alcohol intake and late-stage promotion of breast cancer,” European Journal of Cancer, Vol. 35, pp. 1653–1658, 1999.
[44] L. S. Augustin, L. Dal Maso, C. La Vecchia, M. Parpinel, and E. Negri, “Dietary glycemic index and glycemic load, and breast cancer risk: A case-control study,” Annals of Oncology, Vol. 12, pp. 1533–1538, 2001.
[45] C. R. Jonas, M. L. Mc Cullough, L. R. Teras, K. A. Walker-Thurmond, and M. J. Thun, “Dietary glycemic index, glycemic load, and risk of incident breast cancer in postmenopausal women,” Cancer Epidemiol Biomarkers Prevention, Vol. 12, pp. 573–577, 2003.
[46] S. Bowker, P. Veugelers, S. Majumdar, and J. Johnson, “Increased cancer-related mortality for patients with type 2 diabetes who use sulfonylureas or insulin,” Diabetes Care, Vol. 29, pp. 254–258, 2006.
[47] S. Larsson, C. Mantzoros, and A. Wollk, “Diabetes mellitus and risk of breast cancer: A meta analysis,” International Journal of Cancer, Vol. 121, pp. 856–862, 2007.
[48] P. Muty, T. Quattrin, B. J. B. Grant, V. Krogh, and A. Micheli, “Fasting glucose is a risk factor for breast cancer: a prospective study,” Cancer Epidemiol Biomarkers Prevention, Vol. 11, pp. 1361–1368, 2002.
[49] E. Barrett-Connor, S. Slone, G. Greendale, D. Kritz-Silverstein, and M. Espeland, “The Postmenopausal Estrogen/Progestin Interventions Study: Primary outcomes in adherent women,” Maturitas, Vol. 27, pp. 261–274, 1997.
[50] A. Fournier, S. Mesrine, M. C. Boutron-Ruault, and F. Clavel-Chapelon, “Estrogen-progestogen menopausal hormone therapy and breast cancer: Does delay from menopause onset to treatment initiation influence risks?” Journal of Clinical Oncology, 2009.
[51] W. K. Hou, Y. X. Xu, T. Yu, L. Zhang, and W. W. Zhang, “Adipocytokines and breast cancer risk,” Chinese Medical Journal, Vol. 120, pp. 1592–1596, 2007.
[52] J. H. Kang, B. Y. Yu, and D. S. Youn, “Relationship of serum adiponectin and resistin levels with breast cancer risk,” Journal of Korean Medical Science, Vol. 22, pp. 117–121, 2007.
[53] S. Perrier, F. Caldefie-Chézet, and M. P. Vasson, “IL-1 family in breast cancer: Potential interplay with leptin and other adipocykine,” FEBS letter, Vol. 583, pp. 259–265, 2009.
[54] K. Hancke, D. Grubeck, N. Hauser, R. Kreienberg, and J. M. Weiss, “Adipocyte fatty acid-binding protein as a novel prognostic factor in obese breast cancer patients,” Breast Cancer Research and Treatment, Vol. 119, pp. 367–377, 2010.

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