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Published in: Reproductive Biology and Endocrinology 1/2014

Open Access 01-12-2014 | Research

The role of hormones and aromatase inhibitors on breast tumor growth and general health in a postmenopausal mouse model

Authors: Arunkumar Arumugam, Elaine A Lissner, Rajkumar Lakshmanaswamy

Published in: Reproductive Biology and Endocrinology | Issue 1/2014

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Abstract

Background

Breast cancer is the most frequently diagnosed cancer in women in the United States. Approximately 70% of breast cancers are diagnosed in postmenopausal women. Major clinical trials and experimental studies showed that aromatase inhibitors are effective against postmenopausal breast cancer. Despite their effectiveness in reducing tumor recurrence, aromatase inhibitors have adverse effects on the cardiovascular system and increase osteoporosis and bone fractures. Our study is aimed at investigating the role of natural steroid hormones on serum cardiovascular and bone resorption markers in an established mouse model mimicking postmenopausal breast cancer.

Methods

Ovariectomized nude mice were transplanted with MCF-7 breast cancer cells constitutively expressing aromatase. The mice were treated with different combinations and doses of steroids, [estrogen (25 pg, 40 pg, 100 pg), progesterone (6 ng) and testosterone (50 ng)] along with dehydroepiandrostenedione (100 ug). Serum levels of HDL, LDL/VLDL, free and total cholesterol, total and bone specific alkaline phosphatase and triglycerides were analyzed after 5, 10 and 15 months.

Results

Free cholesterol and LDL/VLDL levels in serum were reduced in groups mimicking estrous cycle and menstrual cycle hormones treatment. HDL cholesterol was increased in all the hormone treated groups except the estrous cycle-mimicking group. Bone specific alkaline phosphatase was decreased in menstrual cycle levels of estrogen and progesterone treatment.

Conclusions

All together our results show that use of natural hormones in appropriate combinations have beneficial effects on cardiac and bone toxicity, along with better tumor reduction than current treatments.
Appendix
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Literature
1.
go back to reference Bray F, Ren JS, Masuyer E, Ferlay J: Global estimates of cancer prevalence for 27 sites in the adult population in 2008. Int J Cancer. 2013, 132 (5): 1133-1145.CrossRefPubMed Bray F, Ren JS, Masuyer E, Ferlay J: Global estimates of cancer prevalence for 27 sites in the adult population in 2008. Int J Cancer. 2013, 132 (5): 1133-1145.CrossRefPubMed
2.
3.
go back to reference Howlader N, Altekruse SF, Li CI, Chen VW, Clarke CA, Ries LA, Cronin KA: US Incidence of Breast Cancer Subtypes Defined by Joint Hormone Receptor and HER2 Status. J Natl Cancer Inst. 2014, 106: 5-doi:10.1093/jnci/dju055CrossRef Howlader N, Altekruse SF, Li CI, Chen VW, Clarke CA, Ries LA, Cronin KA: US Incidence of Breast Cancer Subtypes Defined by Joint Hormone Receptor and HER2 Status. J Natl Cancer Inst. 2014, 106: 5-doi:10.1093/jnci/dju055CrossRef
4.
go back to reference Nilas L, Christiansen C: Bone mass and its relationship to age and the menopause. J Clin Endocrinol Metab. 1987, 65 (4): 697-702.CrossRefPubMed Nilas L, Christiansen C: Bone mass and its relationship to age and the menopause. J Clin Endocrinol Metab. 1987, 65 (4): 697-702.CrossRefPubMed
5.
go back to reference Barrett-Connor E, Bush TL: Estrogen and coronary heart disease in women. JAMA. 1991, 265 (14): 1861-1867.CrossRefPubMed Barrett-Connor E, Bush TL: Estrogen and coronary heart disease in women. JAMA. 1991, 265 (14): 1861-1867.CrossRefPubMed
6.
go back to reference Gambrell RD, Teran AZ: Changes in lipids and lipoproteins with long-term estrogen deficiency and hormone replacement therapy. Am J Obstet Gynecol. 1991, 165 (2): 307-315. discussion 315–317CrossRefPubMed Gambrell RD, Teran AZ: Changes in lipids and lipoproteins with long-term estrogen deficiency and hormone replacement therapy. Am J Obstet Gynecol. 1991, 165 (2): 307-315. discussion 315–317CrossRefPubMed
7.
go back to reference Stampfer MJ, Colditz GA, Willett WC, Manson JE, Rosner B, Speizer FE, Hennekens CH: Postmenopausal estrogen therapy and cardiovascular disease, Ten-year follow-up from the nurses’ health study. N Engl J Med. 1991, 325 (11): 756-762.CrossRefPubMed Stampfer MJ, Colditz GA, Willett WC, Manson JE, Rosner B, Speizer FE, Hennekens CH: Postmenopausal estrogen therapy and cardiovascular disease, Ten-year follow-up from the nurses’ health study. N Engl J Med. 1991, 325 (11): 756-762.CrossRefPubMed
8.
go back to reference Coope J, Thomson JM, Poller L: Effects of “natural oestrogen” replacement therapy on menopausal symptoms and blood clotting. Br Med J. 1975, 4 (5989): 139-143.PubMedCentralCrossRefPubMed Coope J, Thomson JM, Poller L: Effects of “natural oestrogen” replacement therapy on menopausal symptoms and blood clotting. Br Med J. 1975, 4 (5989): 139-143.PubMedCentralCrossRefPubMed
9.
go back to reference Lobo RA: Ovarian hyperandrogenism and androgen-producing tumors. Endocrinol Metab Clin North Am. 1991, 20 (4): 773-805.PubMed Lobo RA: Ovarian hyperandrogenism and androgen-producing tumors. Endocrinol Metab Clin North Am. 1991, 20 (4): 773-805.PubMed
10.
go back to reference Limouzin-Lamothe MA, Mairon N, Joyce CR, Le Gal M: Quality of life after the menopause: influence of hormonal replacement therapy. Am J Obstet Gynecol. 1994, 170 (2): 618-624.CrossRefPubMed Limouzin-Lamothe MA, Mairon N, Joyce CR, Le Gal M: Quality of life after the menopause: influence of hormonal replacement therapy. Am J Obstet Gynecol. 1994, 170 (2): 618-624.CrossRefPubMed
11.
go back to reference Cauley JA, Seeley DG, Ensrud K, Ettinger B, Black D, Cummings SR: Estrogen replacement therapy and fractures in older women, Study of Osteoporotic Fractures Research Group. Ann Intern Med. 1995, 122 (1): 9-16.CrossRefPubMed Cauley JA, Seeley DG, Ensrud K, Ettinger B, Black D, Cummings SR: Estrogen replacement therapy and fractures in older women, Study of Osteoporotic Fractures Research Group. Ann Intern Med. 1995, 122 (1): 9-16.CrossRefPubMed
13.
go back to reference Rossouw JE, Anderson GL, Prentice RL, LaCroix AZ, Kooperberg C, Stefanick ML, Jackson RD, Beresford SA, Howard BV, Johnson KC, Kotchen JM, Ockene J, Writing Group for the Women’s Health Initiative Investigators: Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results From the Women’s Health Initiative randomized controlled trial. JAMA. 2002, 288 (3): 321-333.CrossRefPubMed Rossouw JE, Anderson GL, Prentice RL, LaCroix AZ, Kooperberg C, Stefanick ML, Jackson RD, Beresford SA, Howard BV, Johnson KC, Kotchen JM, Ockene J, Writing Group for the Women’s Health Initiative Investigators: Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results From the Women’s Health Initiative randomized controlled trial. JAMA. 2002, 288 (3): 321-333.CrossRefPubMed
14.
go back to reference Bentrem DJ, Jordan VC: Targeted antiestrogens for the prevention of breast cancer. Oncol Res. 1999, 11 (9): 401-407.PubMed Bentrem DJ, Jordan VC: Targeted antiestrogens for the prevention of breast cancer. Oncol Res. 1999, 11 (9): 401-407.PubMed
15.
go back to reference Jordan VC: Chemoprevention in the 21st century: is a balance best or should women have no estrogen at all?. J Clin Oncol. 2005, 23 (8): 1598-1600.CrossRefPubMed Jordan VC: Chemoprevention in the 21st century: is a balance best or should women have no estrogen at all?. J Clin Oncol. 2005, 23 (8): 1598-1600.CrossRefPubMed
16.
go back to reference Uray IP, Brown PH: Prevention of breast cancer: current state of the science and future opportunities. Expert Opin Investig Drugs. 2006, 15 (12): 1583-1600.CrossRefPubMed Uray IP, Brown PH: Prevention of breast cancer: current state of the science and future opportunities. Expert Opin Investig Drugs. 2006, 15 (12): 1583-1600.CrossRefPubMed
17.
go back to reference Di Prospero LS, Seminsky M, Honeyford J, Doan B, Franssen E, Meschino W, Chart P, Warner E: Psychosocial issues following a positive result of genetic testing for BRCA1 and BRCA2 mutations: findings from a focus group and a needs-assessment survey. CMAJ. 2001, 164 (7): 1005-1009.PubMedCentralPubMed Di Prospero LS, Seminsky M, Honeyford J, Doan B, Franssen E, Meschino W, Chart P, Warner E: Psychosocial issues following a positive result of genetic testing for BRCA1 and BRCA2 mutations: findings from a focus group and a needs-assessment survey. CMAJ. 2001, 164 (7): 1005-1009.PubMedCentralPubMed
18.
go back to reference MacMahon B, Cole P, Lin TM, Lowe CR, Mirra AP, Ravnihar B, Salber EJ, Valaoras VG, Yuasa S: Age at first birth and breast cancer risk. Bull World Health Organ. 1970, 43 (2): 209-221.PubMedCentralPubMed MacMahon B, Cole P, Lin TM, Lowe CR, Mirra AP, Ravnihar B, Salber EJ, Valaoras VG, Yuasa S: Age at first birth and breast cancer risk. Bull World Health Organ. 1970, 43 (2): 209-221.PubMedCentralPubMed
19.
20.
go back to reference Aydiner A: Meta-analysis of breast cancer outcome and toxicity in adjuvant trials of aromatase inhibitors in postmenopausal women. Breast. 2013, 22 (2): 121-129.CrossRefPubMed Aydiner A: Meta-analysis of breast cancer outcome and toxicity in adjuvant trials of aromatase inhibitors in postmenopausal women. Breast. 2013, 22 (2): 121-129.CrossRefPubMed
21.
go back to reference Hershman DL, Kushi LH, Shao T, Buono D, Kershenbaum A, Tsai WY, Fehrenbacher L, Gomez SL, Miles S, Neugut AI: Early discontinuation and nonadherence to adjuvant hormonal therapy in a cohort of 8,769 early-stage breast cancer patients. J Clin Oncol. 2010, 28 (27): 4120-4128.PubMedCentralCrossRefPubMed Hershman DL, Kushi LH, Shao T, Buono D, Kershenbaum A, Tsai WY, Fehrenbacher L, Gomez SL, Miles S, Neugut AI: Early discontinuation and nonadherence to adjuvant hormonal therapy in a cohort of 8,769 early-stage breast cancer patients. J Clin Oncol. 2010, 28 (27): 4120-4128.PubMedCentralCrossRefPubMed
22.
go back to reference Li L, Ding J, Marshall C, Gao J, Hu G, Xiao M: Pretraining affects Morris water maze performance with different patterns between control and ovariectomized plus D-galactose-injected mice. Behav Brain Res. 2011, 217 (1): 244-247.CrossRefPubMed Li L, Ding J, Marshall C, Gao J, Hu G, Xiao M: Pretraining affects Morris water maze performance with different patterns between control and ovariectomized plus D-galactose-injected mice. Behav Brain Res. 2011, 217 (1): 244-247.CrossRefPubMed
23.
go back to reference Eastell R, Hannon RA: Biomarkers of bone health and osteoporosis risk. Proc Nutr Soc. 2008, 67 (2): 157-162.CrossRefPubMed Eastell R, Hannon RA: Biomarkers of bone health and osteoporosis risk. Proc Nutr Soc. 2008, 67 (2): 157-162.CrossRefPubMed
24.
go back to reference Goodman MP: Are all estrogens created equal? A review of oral vs. transdermal therapy. J Womens Health (Larchmt). 2012, 21 (2): 161-169.CrossRef Goodman MP: Are all estrogens created equal? A review of oral vs. transdermal therapy. J Womens Health (Larchmt). 2012, 21 (2): 161-169.CrossRef
25.
go back to reference Stanosz S, Zochowska E, Safranow K, Sieja K, Stanosz M: Influence of modified transdermal hormone replacement therapy on the concentrations of hormones, growth factors, and bone mineral density in women with osteopenia. Metabolism. 2009, 58 (1): 1-7.CrossRefPubMed Stanosz S, Zochowska E, Safranow K, Sieja K, Stanosz M: Influence of modified transdermal hormone replacement therapy on the concentrations of hormones, growth factors, and bone mineral density in women with osteopenia. Metabolism. 2009, 58 (1): 1-7.CrossRefPubMed
26.
go back to reference Davey DA: Update: estrogen and estrogen plus progestin therapy in the care of women at and after the menopause. Womens Health (Lond Engl). 2012, 8 (2): 169-189.CrossRef Davey DA: Update: estrogen and estrogen plus progestin therapy in the care of women at and after the menopause. Womens Health (Lond Engl). 2012, 8 (2): 169-189.CrossRef
27.
go back to reference Maki PM: Minireview: effects of different HT formulations on cognition. Endocrinology. 2012, 153 (8): 3564-3570.CrossRefPubMed Maki PM: Minireview: effects of different HT formulations on cognition. Endocrinology. 2012, 153 (8): 3564-3570.CrossRefPubMed
28.
go back to reference Mueck AO: Postmenopausal hormone replacement therapy and cardiovascular disease: the value of transdermal estradiol and micronized progesterone. Climacteric. 2012, 15 (Suppl 1): 11-17.CrossRefPubMed Mueck AO: Postmenopausal hormone replacement therapy and cardiovascular disease: the value of transdermal estradiol and micronized progesterone. Climacteric. 2012, 15 (Suppl 1): 11-17.CrossRefPubMed
29.
go back to reference Archer DF, Oger E: Estrogen and progestogen effect on venous thromboembolism in menopausal women. Climacteric. 2012, 15 (3): 235-240.CrossRefPubMed Archer DF, Oger E: Estrogen and progestogen effect on venous thromboembolism in menopausal women. Climacteric. 2012, 15 (3): 235-240.CrossRefPubMed
30.
go back to reference Canonico M, Plu-Bureau G, Scarabin PY: Progestogens and venous thromboembolism among postmenopausal women using hormone therapy. Maturitas. 2011, 70 (4): 354-360.CrossRefPubMed Canonico M, Plu-Bureau G, Scarabin PY: Progestogens and venous thromboembolism among postmenopausal women using hormone therapy. Maturitas. 2011, 70 (4): 354-360.CrossRefPubMed
31.
go back to reference Simon JA: What’s new in hormone replacement therapy: focus on transdermal estradiol and micronized progesterone. Climacteric. 2012, 15 (Suppl 1): 3-10.CrossRefPubMed Simon JA: What’s new in hormone replacement therapy: focus on transdermal estradiol and micronized progesterone. Climacteric. 2012, 15 (Suppl 1): 3-10.CrossRefPubMed
32.
go back to reference Davison S, Thipphawong J, Blanchard J, Liu K, Morishige R, Gonda I, Okikawa J, Adams J, Evans A, Otulana B, Davis S: Pharmacokinetics and acute safety of inhaled testosterone in postmenopausal women. J Clin Pharmacol. 2005, 45 (2): 177-184.CrossRefPubMed Davison S, Thipphawong J, Blanchard J, Liu K, Morishige R, Gonda I, Okikawa J, Adams J, Evans A, Otulana B, Davis S: Pharmacokinetics and acute safety of inhaled testosterone in postmenopausal women. J Clin Pharmacol. 2005, 45 (2): 177-184.CrossRefPubMed
33.
go back to reference Montalcini T, Gorgone G, Gazzaruso C, Sesti G, Perticone F, Pujia A: Endogenous testosterone and endothelial function in postmenopausal women. Coron Artery Dis. 2007, 18 (1): 9-13.CrossRefPubMed Montalcini T, Gorgone G, Gazzaruso C, Sesti G, Perticone F, Pujia A: Endogenous testosterone and endothelial function in postmenopausal women. Coron Artery Dis. 2007, 18 (1): 9-13.CrossRefPubMed
34.
go back to reference Pike CJ, Carroll JC, Rosario ER, Barron AM: Protective actions of sex steroid hormones in Alzheimer’s disease. Front Neuroendocrinol. 2009, 30 (2): 239-258.PubMedCentralCrossRefPubMed Pike CJ, Carroll JC, Rosario ER, Barron AM: Protective actions of sex steroid hormones in Alzheimer’s disease. Front Neuroendocrinol. 2009, 30 (2): 239-258.PubMedCentralCrossRefPubMed
35.
go back to reference Glaser RL, Dimitrakakis C: Reduced breast cancer incidence in women treated with subcutaneous testosterone, or testosterone with anastrozole: a prospective, observational study. Maturitas. 2013, 76 (4): 342-349.CrossRefPubMed Glaser RL, Dimitrakakis C: Reduced breast cancer incidence in women treated with subcutaneous testosterone, or testosterone with anastrozole: a prospective, observational study. Maturitas. 2013, 76 (4): 342-349.CrossRefPubMed
36.
go back to reference Dimitrakakis C, Zava D, Marinopoulos S, Tsigginou A, Antsaklis A, Glaser R: Low salivary testosterone levels in patients with breast cancer. BMC Cancer. 2010, 10: 547--10-547PubMedCentralCrossRefPubMed Dimitrakakis C, Zava D, Marinopoulos S, Tsigginou A, Antsaklis A, Glaser R: Low salivary testosterone levels in patients with breast cancer. BMC Cancer. 2010, 10: 547--10-547PubMedCentralCrossRefPubMed
37.
go back to reference Farhat GN, Cummings SR, Chlebowski RT, Parimi N, Cauley JA, Rohan TE, Huang AJ, Vitolins M, Hubbell FA, Manson JE, Cochrane BB, Lane DS, Lee JS: Sex hormone levels and risks of estrogen receptor-negative and estrogen receptor-positive breast cancers. J Natl Cancer Inst. 2011, 103 (7): 562-570.PubMedCentralCrossRefPubMed Farhat GN, Cummings SR, Chlebowski RT, Parimi N, Cauley JA, Rohan TE, Huang AJ, Vitolins M, Hubbell FA, Manson JE, Cochrane BB, Lane DS, Lee JS: Sex hormone levels and risks of estrogen receptor-negative and estrogen receptor-positive breast cancers. J Natl Cancer Inst. 2011, 103 (7): 562-570.PubMedCentralCrossRefPubMed
38.
go back to reference Yue W, Zhou D, Chen S, Brodie A: A new nude mouse model for postmenopausal breast cancer using MCF-7 cells transfected with the human aromatase gene. Cancer Res. 1994, 54 (19): 5092-5095.PubMed Yue W, Zhou D, Chen S, Brodie A: A new nude mouse model for postmenopausal breast cancer using MCF-7 cells transfected with the human aromatase gene. Cancer Res. 1994, 54 (19): 5092-5095.PubMed
39.
go back to reference Brodie AH, Jelovac D, Long B: The intratumoral aromatase model: studies with aromatase inhibitors and antiestrogens. J Steroid Biochem Mol Biol. 2003, 86 (3–5): 283-288.CrossRefPubMed Brodie AH, Jelovac D, Long B: The intratumoral aromatase model: studies with aromatase inhibitors and antiestrogens. J Steroid Biochem Mol Biol. 2003, 86 (3–5): 283-288.CrossRefPubMed
40.
go back to reference Simpson ER, Mahendroo MS, Means GD, Kilgore MW, Hinshelwood MM, Graham-Lorence S, Amarneh B, Ito Y, Fisher CR, Michael MD: Aromatase cytochrome P450, the enzyme responsible for estrogen biosynthesis. Endocr Rev. 1994, 15 (3): 342-355.PubMed Simpson ER, Mahendroo MS, Means GD, Kilgore MW, Hinshelwood MM, Graham-Lorence S, Amarneh B, Ito Y, Fisher CR, Michael MD: Aromatase cytochrome P450, the enzyme responsible for estrogen biosynthesis. Endocr Rev. 1994, 15 (3): 342-355.PubMed
41.
go back to reference Kellis JT, Vickery LE: Purification and characterization of human placental aromatase cytochrome P-450. J Biol Chem. 1987, 262 (9): 4413-4420.PubMed Kellis JT, Vickery LE: Purification and characterization of human placental aromatase cytochrome P-450. J Biol Chem. 1987, 262 (9): 4413-4420.PubMed
42.
go back to reference Rich RL, Hoth LR, Geoghegan KF, Brown TA, LeMotte PK, Simons SP, Hensley P, Myszka DG: Kinetic analysis of estrogen receptor/ligand interactions. Proc Natl Acad Sci U S A. 2002, 99 (13): 8562-8567.PubMedCentralCrossRefPubMed Rich RL, Hoth LR, Geoghegan KF, Brown TA, LeMotte PK, Simons SP, Hensley P, Myszka DG: Kinetic analysis of estrogen receptor/ligand interactions. Proc Natl Acad Sci U S A. 2002, 99 (13): 8562-8567.PubMedCentralCrossRefPubMed
43.
go back to reference Zhu BT, Han GZ, Shim JY, Wen Y, Jiang XR: Quantitative structure-activity relationship of various endogenous estrogen metabolites for human estrogen receptor alpha and beta subtypes: Insights into the structural determinants favoring a differential subtype binding. Endocrinology. 2006, 147 (9): 4132-4150.CrossRefPubMed Zhu BT, Han GZ, Shim JY, Wen Y, Jiang XR: Quantitative structure-activity relationship of various endogenous estrogen metabolites for human estrogen receptor alpha and beta subtypes: Insights into the structural determinants favoring a differential subtype binding. Endocrinology. 2006, 147 (9): 4132-4150.CrossRefPubMed
44.
go back to reference O’Neill JS, Elton RA, Miller WR: Aromatase activity in adipose tissue from breast quadrants: a link with tumour site. Br Med J (Clin Res Ed). 1988, 296 (6624): 741-743.CrossRef O’Neill JS, Elton RA, Miller WR: Aromatase activity in adipose tissue from breast quadrants: a link with tumour site. Br Med J (Clin Res Ed). 1988, 296 (6624): 741-743.CrossRef
45.
go back to reference Bulun SE, Price TM, Aitken J, Mahendroo MS, Simpson ER: A link between breast cancer and local estrogen biosynthesis suggested by quantification of breast adipose tissue aromatase cytochrome P450 transcripts using competitive polymerase chain reaction after reverse transcription. J Clin Endocrinol Metab. 1993, 77 (6): 1622-1628.PubMed Bulun SE, Price TM, Aitken J, Mahendroo MS, Simpson ER: A link between breast cancer and local estrogen biosynthesis suggested by quantification of breast adipose tissue aromatase cytochrome P450 transcripts using competitive polymerase chain reaction after reverse transcription. J Clin Endocrinol Metab. 1993, 77 (6): 1622-1628.PubMed
46.
go back to reference Sabnis GJ, Jelovac D, Long B, Brodie A: The role of growth factor receptor pathways in human breast cancer cells adapted to long-term estrogen deprivation. Cancer Res. 2005, 65 (9): 3903-3910.CrossRefPubMed Sabnis GJ, Jelovac D, Long B, Brodie A: The role of growth factor receptor pathways in human breast cancer cells adapted to long-term estrogen deprivation. Cancer Res. 2005, 65 (9): 3903-3910.CrossRefPubMed
47.
go back to reference Jelovac D, Sabnis G, Long BJ, Macedo L, Goloubeva OG, Brodie AM: Activation of mitogen-activated protein kinase in xenografts and cells during prolonged treatment with aromatase inhibitor letrozole. Cancer Res. 2005, 65 (12): 5380-5389.CrossRefPubMed Jelovac D, Sabnis G, Long BJ, Macedo L, Goloubeva OG, Brodie AM: Activation of mitogen-activated protein kinase in xenografts and cells during prolonged treatment with aromatase inhibitor letrozole. Cancer Res. 2005, 65 (12): 5380-5389.CrossRefPubMed
48.
go back to reference Jelovac D, Macedo L, Goloubeva OG, Handratta V, Brodie AM: Additive antitumor effect of aromatase inhibitor letrozole and antiestrogen fulvestrant in a postmenopausal breast cancer model. Cancer Res. 2005, 65 (12): 5439-5444.CrossRefPubMed Jelovac D, Macedo L, Goloubeva OG, Handratta V, Brodie AM: Additive antitumor effect of aromatase inhibitor letrozole and antiestrogen fulvestrant in a postmenopausal breast cancer model. Cancer Res. 2005, 65 (12): 5439-5444.CrossRefPubMed
49.
go back to reference Eastell R, Adams JE, Coleman RE, Howell A, Hannon RA, Cuzick J, Mackey JR, Beckmann MW, Clack G: Effect of anastrozole on bone mineral density: 5-year results from the anastrozole, tamoxifen, alone or in combination trial 18233230. J Clin Oncol. 2008, 26 (7): 1051-1057.CrossRefPubMed Eastell R, Adams JE, Coleman RE, Howell A, Hannon RA, Cuzick J, Mackey JR, Beckmann MW, Clack G: Effect of anastrozole on bone mineral density: 5-year results from the anastrozole, tamoxifen, alone or in combination trial 18233230. J Clin Oncol. 2008, 26 (7): 1051-1057.CrossRefPubMed
50.
go back to reference Sestak I, Sapunar F, Cuzick J: Aromatase inhibitor-induced carpal tunnel syndrome: results from the ATAC trial. J Clin Oncol. 2009, 27 (30): 4961-4965.CrossRefPubMed Sestak I, Sapunar F, Cuzick J: Aromatase inhibitor-induced carpal tunnel syndrome: results from the ATAC trial. J Clin Oncol. 2009, 27 (30): 4961-4965.CrossRefPubMed
51.
go back to reference Cuzick J, Sestak I, Cella D, Fallowfield L, ATAC Trialists’ Group: Treatment-emergent endocrine symptoms and the risk of breast cancer recurrence: a retrospective analysis of the ATAC trial. Lancet Oncol. 2008, 9 (12): 1143-1148.CrossRefPubMed Cuzick J, Sestak I, Cella D, Fallowfield L, ATAC Trialists’ Group: Treatment-emergent endocrine symptoms and the risk of breast cancer recurrence: a retrospective analysis of the ATAC trial. Lancet Oncol. 2008, 9 (12): 1143-1148.CrossRefPubMed
52.
go back to reference Cuzick J, Sestak I, Baum M, Buzdar A, Howell A, Dowsett M, Forbes JF, ATAC/LATTE investigators: Effect of anastrozole and tamoxifen as adjuvant treatment for early-stage breast cancer: 10-year analysis of the ATAC trial. Lancet Oncol. 2010, 11 (12): 1135-1141.CrossRefPubMed Cuzick J, Sestak I, Baum M, Buzdar A, Howell A, Dowsett M, Forbes JF, ATAC/LATTE investigators: Effect of anastrozole and tamoxifen as adjuvant treatment for early-stage breast cancer: 10-year analysis of the ATAC trial. Lancet Oncol. 2010, 11 (12): 1135-1141.CrossRefPubMed
53.
go back to reference Tannock IF: 10-year analysis of the ATAC trial: wrong conclusion?. Lancet Oncol. 2011, 12 (3): 216-217. author reply 217CrossRefPubMed Tannock IF: 10-year analysis of the ATAC trial: wrong conclusion?. Lancet Oncol. 2011, 12 (3): 216-217. author reply 217CrossRefPubMed
54.
go back to reference Salpeter SR, Walsh JM, Ormiston TM, Greyber E, Buckley NS, Salpeter EE: Meta-analysis: effect of hormone-replacement therapy on components of the metabolic syndrome in postmenopausal women. Diabetes Obes Metab. 2006, 8 (5): 538-554.CrossRefPubMed Salpeter SR, Walsh JM, Ormiston TM, Greyber E, Buckley NS, Salpeter EE: Meta-analysis: effect of hormone-replacement therapy on components of the metabolic syndrome in postmenopausal women. Diabetes Obes Metab. 2006, 8 (5): 538-554.CrossRefPubMed
55.
go back to reference The Writing Group for the PEPI Trial: Effects of estrogen or estrogen/progestin regimens on heart disease risk factors in postmenopausal women. The Postmenopausal Estrogen/Progestin Interventions (PEPI) Trial. JAMA. 1995, 273 (3): 199-208.CrossRef The Writing Group for the PEPI Trial: Effects of estrogen or estrogen/progestin regimens on heart disease risk factors in postmenopausal women. The Postmenopausal Estrogen/Progestin Interventions (PEPI) Trial. JAMA. 1995, 273 (3): 199-208.CrossRef
56.
go back to reference Godsland IF, Winkler U, Lidegaard O, Crook D: Occlusive vascular diseases in oral contraceptive users. Epidemiology, pathology and mechanisms. Drugs. 2000, 60 (4): 721-869.CrossRefPubMed Godsland IF, Winkler U, Lidegaard O, Crook D: Occlusive vascular diseases in oral contraceptive users. Epidemiology, pathology and mechanisms. Drugs. 2000, 60 (4): 721-869.CrossRefPubMed
57.
go back to reference Godsland IF, Manassiev NA, Felton CV, Proudler AJ, Crook D, Whitehead MI, Stevenson JC: Effects of low and high dose oestradiol and dydrogesterone therapy on insulin and lipoprotein metabolism in healthy postmenopausal women. Clin Endocrinol (Oxf). 2004, 60 (5): 541-549.CrossRef Godsland IF, Manassiev NA, Felton CV, Proudler AJ, Crook D, Whitehead MI, Stevenson JC: Effects of low and high dose oestradiol and dydrogesterone therapy on insulin and lipoprotein metabolism in healthy postmenopausal women. Clin Endocrinol (Oxf). 2004, 60 (5): 541-549.CrossRef
58.
go back to reference Godsland IF: Biology: risk factor modification by OCs and HRT lipids and lipoproteins. Maturitas. 2004, 47 (4): 299-303.CrossRefPubMed Godsland IF: Biology: risk factor modification by OCs and HRT lipids and lipoproteins. Maturitas. 2004, 47 (4): 299-303.CrossRefPubMed
59.
go back to reference Go AS, Mozaffarian D, Roger VL, Benjamin EJ, Berry JD, Borden WB, Bravata DM, Dai S, Ford ES, Fox CS, Franco S, Fullerton HJ, Gillespie C, Hailpern SM, Heit JA, Howard VJ, Huffman MD, Kissela BM, Kittner SJ, Lackland DT, Lichtman JH, Lisabeth LD, Magid D, Marcus GM, Marelli A, Matchar DB, McGuire DK, Mohler ER, Moy CS, Mussolino ME, et al: Heart disease and stroke statistics–2013 update: a report from the American Heart Association. Circulation. 2013, 127 (1): e6-e245.CrossRefPubMed Go AS, Mozaffarian D, Roger VL, Benjamin EJ, Berry JD, Borden WB, Bravata DM, Dai S, Ford ES, Fox CS, Franco S, Fullerton HJ, Gillespie C, Hailpern SM, Heit JA, Howard VJ, Huffman MD, Kissela BM, Kittner SJ, Lackland DT, Lichtman JH, Lisabeth LD, Magid D, Marcus GM, Marelli A, Matchar DB, McGuire DK, Mohler ER, Moy CS, Mussolino ME, et al: Heart disease and stroke statistics–2013 update: a report from the American Heart Association. Circulation. 2013, 127 (1): e6-e245.CrossRefPubMed
60.
61.
go back to reference Bhavnani BR, Stanczyk FZ: Pharmacology of conjugated equine estrogens: Efficacy, safety and mechanism of action. J Steroid Biochem Mol Biol. 2014, 142: 16-29.CrossRefPubMed Bhavnani BR, Stanczyk FZ: Pharmacology of conjugated equine estrogens: Efficacy, safety and mechanism of action. J Steroid Biochem Mol Biol. 2014, 142: 16-29.CrossRefPubMed
62.
go back to reference Anderson GL, Limacher M, Assaf AR, Bassford T, Beresford SA, Black H, Bonds D, Brunner R, Brzyski R, Caan B, Chlebowski R, Curb D, Gass M, Hays J, Heiss G, Hendrix S, Howard BV, Hsia J, Hubbell A, Jackson R, Johnson KC, Judd H, Kotchen JM, Kuller L, LaCroix AZ, Lane D, Langer RD, Lasser N, Lewis CE, Manson J, et al: Effects of conjugated equine estrogen in postmenopausal women with hysterectomy: the Women’s Health Initiative randomized controlled trial. JAMA. 2004, 291 (14): 1701-1712.CrossRefPubMed Anderson GL, Limacher M, Assaf AR, Bassford T, Beresford SA, Black H, Bonds D, Brunner R, Brzyski R, Caan B, Chlebowski R, Curb D, Gass M, Hays J, Heiss G, Hendrix S, Howard BV, Hsia J, Hubbell A, Jackson R, Johnson KC, Judd H, Kotchen JM, Kuller L, LaCroix AZ, Lane D, Langer RD, Lasser N, Lewis CE, Manson J, et al: Effects of conjugated equine estrogen in postmenopausal women with hysterectomy: the Women’s Health Initiative randomized controlled trial. JAMA. 2004, 291 (14): 1701-1712.CrossRefPubMed
63.
go back to reference Chlebowski RT, Hendrix SL, Langer RD, Stefanick ML, Gass M, Lane D, Rodabough RJ, Gilligan MA, Cyr MG, Thomson CA, Khandekar J, Petrovitch H, McTiernan A, WHI Investigators: Influence of estrogen plus progestin on breast cancer and mammography in healthy postmenopausal women: the Women’s Health Initiative Randomized Trial. JAMA. 2003, 289 (24): 3243-3253.CrossRefPubMed Chlebowski RT, Hendrix SL, Langer RD, Stefanick ML, Gass M, Lane D, Rodabough RJ, Gilligan MA, Cyr MG, Thomson CA, Khandekar J, Petrovitch H, McTiernan A, WHI Investigators: Influence of estrogen plus progestin on breast cancer and mammography in healthy postmenopausal women: the Women’s Health Initiative Randomized Trial. JAMA. 2003, 289 (24): 3243-3253.CrossRefPubMed
64.
go back to reference Ottosson UB, Johansson BG, von Schoultz B: Subfractions of high-density lipoprotein cholesterol during estrogen replacement therapy: a comparison between progestogens and natural progesterone. Am J Obstet Gynecol. 1985, 151 (6): 746-750.CrossRefPubMed Ottosson UB, Johansson BG, von Schoultz B: Subfractions of high-density lipoprotein cholesterol during estrogen replacement therapy: a comparison between progestogens and natural progesterone. Am J Obstet Gynecol. 1985, 151 (6): 746-750.CrossRefPubMed
65.
go back to reference Minshall RD, Stanczyk FZ, Miyagawa K, Uchida B, Axthelm M, Novy M, Hermsmeyer K: Ovarian steroid protection against coronary artery hyperreactivity in rhesus monkeys. J Clin Endocrinol Metab. 1998, 83 (2): 649-659.PubMed Minshall RD, Stanczyk FZ, Miyagawa K, Uchida B, Axthelm M, Novy M, Hermsmeyer K: Ovarian steroid protection against coronary artery hyperreactivity in rhesus monkeys. J Clin Endocrinol Metab. 1998, 83 (2): 649-659.PubMed
66.
go back to reference Mishra RG, Hermsmeyer RK, Miyagawa K, Sarrel P, Uchida B, Stanczyk FZ, Burry KA, Illingworth DR, Nordt FJ: Medroxyprogesterone acetate and dihydrotestosterone induce coronary hyperreactivity in intact male rhesus monkeys. J Clin Endocrinol Metab. 2005, 90 (6): 3706-3714.PubMedCentralCrossRefPubMed Mishra RG, Hermsmeyer RK, Miyagawa K, Sarrel P, Uchida B, Stanczyk FZ, Burry KA, Illingworth DR, Nordt FJ: Medroxyprogesterone acetate and dihydrotestosterone induce coronary hyperreactivity in intact male rhesus monkeys. J Clin Endocrinol Metab. 2005, 90 (6): 3706-3714.PubMedCentralCrossRefPubMed
67.
go back to reference Miyagawa K, Rosch J, Stanczyk F, Hermsmeyer K: Medroxyprogesterone interferes with ovarian steroid protection against coronary vasospasm. Nat Med. 1997, 3 (3): 324-327.CrossRefPubMed Miyagawa K, Rosch J, Stanczyk F, Hermsmeyer K: Medroxyprogesterone interferes with ovarian steroid protection against coronary vasospasm. Nat Med. 1997, 3 (3): 324-327.CrossRefPubMed
68.
go back to reference Saarikoski S, Yliskoski M, Penttila I: Sequential use of norethisterone and natural progesterone in pre-menopausal bleeding disorders. Maturitas. 1990, 12 (2): 89-97.CrossRefPubMed Saarikoski S, Yliskoski M, Penttila I: Sequential use of norethisterone and natural progesterone in pre-menopausal bleeding disorders. Maturitas. 1990, 12 (2): 89-97.CrossRefPubMed
69.
go back to reference Fahraeus L, Larsson-Cohn U, Wallentin L: L-norgestrel and progesterone have different influences on plasma lipoproteins. Eur J Clin Invest. 1983, 13 (6): 447-453.CrossRefPubMed Fahraeus L, Larsson-Cohn U, Wallentin L: L-norgestrel and progesterone have different influences on plasma lipoproteins. Eur J Clin Invest. 1983, 13 (6): 447-453.CrossRefPubMed
70.
go back to reference Ottosson UB: Oral progesterone and estrogen/progestogen therapy. Effects of natural and synthetic hormones on subfractions of HDL cholesterol and liver proteins. Acta Obstet Gynecol Scand Suppl. 1984, 127: 1-37.CrossRefPubMed Ottosson UB: Oral progesterone and estrogen/progestogen therapy. Effects of natural and synthetic hormones on subfractions of HDL cholesterol and liver proteins. Acta Obstet Gynecol Scand Suppl. 1984, 127: 1-37.CrossRefPubMed
72.
73.
go back to reference Harada S, Rodan GA: Control of osteoblast function and regulation of bone mass. Nature. 2003, 423 (6937): 349-355.CrossRefPubMed Harada S, Rodan GA: Control of osteoblast function and regulation of bone mass. Nature. 2003, 423 (6937): 349-355.CrossRefPubMed
74.
go back to reference Harman SM: Estrogen replacement in menopausal women: recent and current prospective studies, the WHI and the KEEPS. Gend Med. 2006, 3 (4): 254-269.CrossRefPubMed Harman SM: Estrogen replacement in menopausal women: recent and current prospective studies, the WHI and the KEEPS. Gend Med. 2006, 3 (4): 254-269.CrossRefPubMed
75.
go back to reference Christiansen C, Riis BJ, Nilas L, Rodbro P, Deftos L: Uncoupling of bone formation and resorption by combined oestrogen and progestagen therapy in postmenopausal osteoporosis. Lancet. 1985, 2 (8459): 800-801.CrossRefPubMed Christiansen C, Riis BJ, Nilas L, Rodbro P, Deftos L: Uncoupling of bone formation and resorption by combined oestrogen and progestagen therapy in postmenopausal osteoporosis. Lancet. 1985, 2 (8459): 800-801.CrossRefPubMed
76.
go back to reference Tremollieres F, Pouilles JM, Ribot C: Effect of long-term administration of progestogen on post-menopausal bone loss: result of a two-year, controlled randomized study. Clin Endocrinol (Oxf). 1993, 38 (6): 627-631.CrossRef Tremollieres F, Pouilles JM, Ribot C: Effect of long-term administration of progestogen on post-menopausal bone loss: result of a two-year, controlled randomized study. Clin Endocrinol (Oxf). 1993, 38 (6): 627-631.CrossRef
77.
go back to reference Tremollieres FA, Pouilles JM, Ribot C: Withdrawal of hormone replacement therapy is associated with significant vertebral bone loss in postmenopausal women. Osteoporos Int. 2001, 12 (5): 385-390.CrossRefPubMed Tremollieres FA, Pouilles JM, Ribot C: Withdrawal of hormone replacement therapy is associated with significant vertebral bone loss in postmenopausal women. Osteoporos Int. 2001, 12 (5): 385-390.CrossRefPubMed
78.
go back to reference Seifert-Klauss V, Schmidmayr M, Hobmaier E, Wimmer T: Progesterone and bone: a closer link than previously realized. Climacteric. 2012, 15 (Suppl 1): 26-31.CrossRefPubMed Seifert-Klauss V, Schmidmayr M, Hobmaier E, Wimmer T: Progesterone and bone: a closer link than previously realized. Climacteric. 2012, 15 (Suppl 1): 26-31.CrossRefPubMed
Metadata
Title
The role of hormones and aromatase inhibitors on breast tumor growth and general health in a postmenopausal mouse model
Authors
Arunkumar Arumugam
Elaine A Lissner
Rajkumar Lakshmanaswamy
Publication date
01-12-2014
Publisher
BioMed Central
Published in
Reproductive Biology and Endocrinology / Issue 1/2014
Electronic ISSN: 1477-7827
DOI
https://doi.org/10.1186/1477-7827-12-66

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