The potency and clinical efficacy of aromatase inhibitors across the breast cancer continuum

Annals of Oncology

Volumn 22, Issue 3, 2011, Pages 503-514

  Lonning P E ^a  

^a UNIVERSITY OF BERGEN   (Norway)

Author keywords

Anastrozole; Aromatase inhibitor; Breast cancer; Estrogen; Exemestane; Letrozole

Indexed keywords

AMINOGLUTETHIMIDE; ANASTROZOLE; AROMATASE; AROMATASE INHIBITOR; ESTROGEN; EXEMESTANE; FADROZOLE; FORMESTANE; FULVESTRANT; LETROZOLE; PLACEBO; PYRIDOGLUTETHIMIDE; TAMOXIFEN; TAMOXIFEN CITRATE; ZOLEDRONIC ACID;

ARTHRALGIA; BREAST CANCER; CANCER ADJUVANT THERAPY; CANCER COMBINATION CHEMOTHERAPY; CARDIOVASCULAR DISEASE; CLINICAL TRIAL; DRUG ANTAGONISM; DRUG EFFICACY; DRUG POTENCY; DRUG TARGETING; ENZYME INHIBITION; EVENT FREE SURVIVAL; HUMAN; MONOTHERAPY; OSTEOPOROSIS; POSTMENOPAUSE; PRIORITY JOURNAL; REVIEW; TENDON DISEASE; TREATMENT DURATION;

ANTINEOPLASTIC AGENTS; AROMATASE; AROMATASE INHIBITORS; BREAST NEOPLASMS; CHEMOTHERAPY, ADJUVANT; CLINICAL TRIALS AS TOPIC; DRUG TOXICITY; ESTROGENS; FEMALE; HUMANS; META-ANALYSIS AS TOPIC; NEOADJUVANT THERAPY; NEOPLASM RECURRENCE, LOCAL; TREATMENT OUTCOME;

EID: 78650884898     PISSN: 09237534     EISSN: 15698041     Source Type: Journal    
DOI: 10.1093/annonc/mdq337     Document Type: Review

References (137)

1. Beatson GT. On the treatment of inoperable cases of carcinoma of the mamma. Suggestions for a new method of treatment with illustrative cases. Lancet 1896; 2: 104-107.
2. Dao TL, Huggins C. Bilateral adrenalectomy in the treatment of cancer of the breast. Arch Surg 1955; 71: 645-657.
3. Luft R, Olivecrona H, Sjögren B. Hypophysektomy in man. Nord Med 1952; 14: 351-354.
4. Fracchia AA, Randall HT, Farrow JH. The results of adrenalectomy in advanced breast cancer in 500 consecutive patients. Surg Gynecol Obstet 1967; 125: 747-756.
5. Fracchia AA, Farrow JH, Miller TR. et al. Hypophysectomy as compared with adrenalectomy in the treatment of advanced carcinoma of the breast. Surg Gynecol Obst 1971; 133: 241-246.
6. Lemon HM. Prednisone therapy of advanced mammary cancer. Cancer 1959; 12: 93-107.
7. Taylor SG, Ayer JP, Morris RS. Cortical steroids in treatment of cancer. JAMA 1950; 144: 1058-1064.
8. De Coster R, Caers I, Haelterman C, Debroye M. Effect of a single administration of ketoconazole on total and physiologically free plasma testosterone and 17 beta-oestradiol levels in healthy male volunteers. Eur J Clin Pharmacol 1985; 29: 489-493.
9. Harris AL, Cantwell BM, Dowsett M. High dose ketoconazole: endocrine and therapeutic effects in postmenopausal breast cancer. Br J Cancer 1988; 58: 493-496.
10. Cash R, Brough AJ, Cohen MNP, Satoh PS. Aminoglutethimide (Elipten-Ciba) is an inhibitor of adrenal steroidogenesis: mechanism of action and therapeutic trial. J Clin Endocrinol Metab 1967; 27: 1239-1248.
11. Lipton A, Harvey HA, Santen RJ. et al. Randomized trial of aminoglutethimide versus tamoxifen in metastatic breast cancer. Cancer Res 1982; 42 (8 Suppl): 3434s-3436s.
12. Harvey HA, Lipton A, White DS. et al. Cross-over comparison of tamoxifen and aminoglutethimide in advanced breast cancer. Cancer Res 1982; 42 (8 Suppl): 3451s-3453s.
13. Smith IE, Harris AL, Morgan M. et al. Tamoxifen versus aminoglutethimide in advanced breast carcinoma: a randomized cross-over trial. Br Med J (Clin Res Ed) 1981; 283: 1432-1434.
14. Santen RJ, Worgul TJ, Lipton A. et al. Aminoglutethimide as treatment of postmenopausal women with advanced breast carcinoma. Ann Intern Med 1982; 96: 94-101.
15. Vermeulen A, Paridaens R, Heuson JC. Effects of aminoglutethimide on adrenal steroid secretion. Clin Endocrinol (Oxf) 1983; 19: 673-682.
16. Samojlik E, Veldhuis JD, Wells SA, Santen RJ. Preservation of androgen secretion during estrogen suppression with aminoglutethimide in the treatment of metastatic breast carcinoma. J Clin Invest 1980; 65: 602-612.
17. Santen RJ, Santner S, Davis B. et al. Aminoglutethimide inhibits extraglandular estrogen production in postmenopausal women with breast carcinoma. J Clin Endocrinol Metab 1978; 47: 1257-1265.
18. Brodie AMH, Schwarzel WC, Shaikh AA, Brodie HJ. The effect of an aromatase inhibitor, 4-hydroxy-androstene-3,17-dione, on estrogen-dependent processes in reproduction and breast cancer. Endocrinology 1977; 100: 1684-1695.
19. Brodie AMH, Marsh D, Brodie HJ. Aromatase inhibitors-IV. Regression of hormone-dependent, mammary tumors in the rat with 4-acetoxy-4-androstene-3,17-dione. J Steroid Biochem 1979; 10: 423-429.
20. Coombes RC, Goss P, Dowsett M. et al. 4-hydroxyandrostenedione in treatment of postmenopausal patients with advanced breast cancer. Lancet 1984; ii: 1237-1239.
21. Ghosh D, Griswold J, Erman M, Pangborn W. Structural basis for androgen specificity and oestrogen synthesis in human aromatase. Nature 2009; 457: 219-223.
22. Bulun SE, Sebastian S, Takayama K. et al. The human CYP19 (aromatase P450) gene: update on physiologic roles and genomic organization of promoters. J Steroid Biochem Mol Biol 2003; 86: 219-224.
23. Agarwal VR, Bulun SE, Leitch M. et al. Use of alternative promoters to express the aromatase cytochrome p450 (CYP19) gene in breast adipose tissues of cancer-free and breast cancer patients. J Clin Endocrinol Metab 1996; 81: 3843-3849.
24. Clyne CD, Kovacic A, Speed CJ. et al. Regulation of aromatase expression by the nuclear receptor LRH-1 in adipose tissue. Mol Cell Endocrinol 2004; 215: 39-44.
25. Zhou J, Suzuki T, Kovacic A. et al. Interactions between prostaglandin E-2, liver receptor homologue-1, and aromatase in breast cancer. Cancer Res 2005; 65: 657-663.
26. Mendelson CR, Jiang B, Shelton JM. et al. Transcriptional regulation of aromatase in placenta and ovary. J Steroid Biochem Mol Biol 2005; 95(1-5): 25-33.
27. Grodin JM, Siiteri PK, MacDonald PC. Source of estrogen production in postmenopausal women. J Clin Endocrinol Metab 1973; 36: 207-214.
28. MacDonald PC, Rombaut RP, Siiteri PK. Plasma precursors of estrogen. I. Extent of conversion of plasma delta-4-androstenedione to estrone in normal males and nonpregnant normal, castrate and adrenalectomized females. J Clin Endocrinol Metab 1967; 27: 1103-1111.
29. Cantilo JA, La Roche G, Novitsky M, Lawrence JH. Conversion of testosterone to estrogens in humans. Acta Isot (Padova) 1962; 1: 351-376.
30. Sluijmer AV, Heineman MA, Jong FH, Evers JLH. Endocrine activity of the postmenopausal ovary: the effects of pituitary down-regulation and oophorectomy. J Clin Endocrinol Metab 1995; 80: 2163-2167.
31. Couzinet B, Meduri G, Lecce MG. et al. The postmenopausal ovary is not a major androgen-producing gland. J Clin Endocrinol Metab 2001; 86: 5060-5066.
32. van Landeghem AJJ, Poortman J, Nabuurs M, Thijssen JHH. Endogenous concentration and subcellular distribution of estrogens in normal and malignant breast tissue. Cancer Res 1985; 45: 2900-2904.
33. Edery M, Goussard J, Dehennin L. et al. Endogenous oestradiol-17ß concentration in breast tumours determined by mass fragmentography and by radioimmunoassay: relationship to receptor content. Eur J Cancer 1981; 17: 115-120.
34. Vermeulen A, Deslypere JP, Paridaens R. et al. Aromatase, 17ß-hydroxysteroid dehydrogenase and intratissular sex hormone concentrations in cancerous and normal glandular breast tissue in postmenopausal women. Eur J Cancer Clin Oncol 1986; 22: 515-525.
35. Miller WR, Telford J, Love C. et al. Effects of letrozole as primary medical therapy on in situ oestrogen synthesis and endogenous oestrogen levels within the breast. Breast 1998; 7: 273-276.
36. Geisler J, Detre S, Berntsen H. et al. Influence of neoadjuvant anastrozole (Arimidex) on intratumoral estrogen levels and proliferation markers in patients with locally advanced breast cancer. Clin Cancer Res 2001; 7: 1230-1236.
37. Geisler J, Helle H, Ekse D. et al. Letrozole is superior to anastrozole in suppressing breast cancer tissue and plasma estrogen levels. Clin Cancer Res 2008; 14: 6330-6335.
38. Shibuya R, Suzuki T, Miki Y. et al. Intratumoral concentration of sex steroids and expression of sex steroid-producing enzymes in ductal carcinoma in situ of human breast. Endocr Relat Cancer 2008; 15: 113-124.
39. Suzuki T, Miki Y, Akahira JI. et al. Aromatase in human breast carcinoma as a key regulator of intratumoral sex steroid concentrations. Endocr J 2008; 55: 455-463.
40. Lønning PE, Helle H, Duong NK. et al. Tissue estradiol is selectively elevated in receptor positive breast cancers while tumour estrone is reduced independent of receptor status. J Steroid Biochem Mol Biol 2009; 117: 31-41.
41. Haines B, Geisler J, Straume AH. et al. Determinants of oestradiol (E2) concentrations in postmenopausal breast cancer: roles for oestrogen receptor (ER) and 17beta hydroxysteroid dehydrogenase (HSD17B7). Clin Cancer Res 2010; 16: 1790-1801.
42. Dunbier AK, Anderson H, Ghazoui Z. et al. Relationship between plasma estradiol levels and estrogen-responsive gene expression in estrogen receptorpositive breast cancer in postmenopausal women. J Clin Oncol 2010; 28: 1161-1167.
43. Dorgan JF, Longcope C, Stanczyk FZ. et al. Plasma sex steroid hormone levels and risk of breast cancer in postmenopausal women. J Natl Cancer Inst 1999; 91: 380-381.
44. Lønning PE, Helle SI, Johannessen DC. et al. Influence of plasma estrogen levels on the length of the disease-free interval in postmenopausal women with breast cancer. Breast Cancer Res Treat 1996; 39: 335-341.
45. Miller WR, Dixon JM. Endocrine and clinical endpoints of exemestane as neoadjuvant therapy. Cancer Control 2002; 9 (2 Suppl): 9-15.
46. Hong Y, Yu B, Sherman M. et al. Molecular basis for the aromatization reaction and exemestane-mediated irreversible inhibition of human aromatase. Mol Endocrinol 2007; 21: 401-414.
47. Haynes BP, Jarman M, Dowsett M. et al. Pharmacokinetics and pharmacodynamics of the aromatase inhibitor 3-ethyl-3-(4-pyridyl)piperidine-2,6-dione in patients with postmenopausal breast cancer. Cancer Chemother Pharmacol 1991; 27: 367-372.
48. Geisler J, Lundgren S, Berntsen H. et al. Influence of dexaminoglutethimide, an optical isomer of aminoglutethimide, on the disposition of estrone sulfate in postmenopausal breast cancer patients. J Clin Endocrinol Metab 1998; 83: 2687-2693.
49. Lønning PE, Jacobs S, Jones A. et al. The influence of CGS 16949A on peripheral aromatisation in breast cancer patients. Br J Cancer 1991; 63: 789-793.
50. Smith IE, Norton A. Fadrozole and letrozole in advanced breast cancer: clinical and biochemical effects. Breast Cancer Res Treat 1998; 49 (Suppl 1): S67-S71.
51. Purba HS, Bhatnagar AS. A comparison of methods measuring aromatase activity in human placenta and rat ovary. J Enzyme Inhib 1990; 4: 169-178.
52. Miller WR, Dixon JM. Antiaromatase agents: preclinical data and neoadjuvant therapy. Clin Breast Cancer 2000; 1 (Suppl. 1): s9-s14.
53. Bhatnagar AS, Batzl C, Hausler A. et al. Pharmacology of nonsteroidal aromatase inhibitors. In Pasqualini JR, Katzenellenbogen B (eds), Hormone-Dependent Cancer. New York: Marcel Dekker, Inc. 1996; 155-168.
54. Dixon JM, Renshaw L, Young O. et al. Letrozole suppresses plasma estradiol and estrone sulphate more completely than anastrozole in postmenopausal women with breast cancer. J Clin Oncol 2008; 26: 1671-1676.
55. Lønning PE, Ekse D. A sensitive assay for measurement of plasma estrone sulphate in patients on treatment with aromatase inhibitors. J Steroid Biochem Mol Biol 1995; 55: 409-412.
56. Geisler J, Ekse D, Helle H. et al. An optimised, highly sensitive radioimmunoassay for the simultaneous measurement of estrone, estradiol and estrone sulfate in the ultra-low range in human plasma samples. J Steroid Biochem Molec Biol 2008; 109: 90-95.
57. Santen RJ, Demers L, Ohorodnik S. et al. Superiority of gas chromatography/tandem mass spectrometry assay (GC/MS/MS) for estradiol for monitoring of aromatase inhibitor therapy. Steroids 2007; 72: 666-671.
58. Geisler J, Haynes B, Anker G. et al. Influence of letrozole (Femara) and anastrozole (Arimidex) on total body aromatization and plasma estrogen levels in postmenopausal breast cancer patients evaluated in a randomized, cross-over-designed study. J Clin Oncol 2002; 20: 751-757.
59. Johannessen DC, Engan T, di Salle E. et al. Endocrine and clinical effects of exemestane (PNU 155971), a novel steroidal aromatase inhibitor, in postmenopausal breast cancer patients: a phase I study. Clin Cancer Res 1997; 3: 1101-1108.
60. Lønning PE, Skulstad P, Sunde A, Thorsen T. Separation of urinary metabolites of radiolabelled estrogens in man by HPLC. J Steroid Biochem 1989; 32: 91-97.
61. Jacobs S, Lønning PE, Haynes B. et al. Measurement of aromatisation by a urine technique suitable for the evaluation of aromatase inhibitors in vivo. J Enzyme Inhib 1991; 4: 315-325.
62. MacNeill FA, Jones AL, Jacobs S. et al. The influence of aminoglutethimide and its analogue rogletimide on peripheral aromatisation in breast cancer. Br J Cancer 1992; 66: 692-697.
63. Jones AL, MacNeill F, Jacobs S. et al. The influence of intramuscular 4-hydroxyandrostenedione on peripheral aromatisation in breast cancer patients. Eur J Cancer 1992; 28A: 1712-1716.
64. MacNeill FA, Jacobs S, Dowsett M. et al. The effects of oral 4-hydroxyandrostenedione on peripheral aromatisation in post-menopausal breast cancer patients. Cancer Chemother Pharmacol 1995; 36: 249-254.
65. MacNeill FA, Jacobs S, Lønning PE. et al. Combined treatment with 4-hydroxyandrostenedione and aminoglutethimide: effects on aromatase inhibition and oestrogen suppression. Br J Cancer 1994; 69: 1171-1175.
66. ®), a selective, non-steroidal aromatase inhibitor, on in vivo aromatisation and plasma oestrogen levels in postmenopausal women with breast cancer. Br J Cancer 1996; 74: 1286-1291.
67. Geisler J, King N, Anker G. et al. In vivo inhibition of aromatization by exemestane, a novel irreversible aromatase inhibitor, in postmenopausal breast cancer patients. Clin Cancer Res 1998; 4: 2089-2093.
68. Smith IE, Dowsett M, Ebbs SR. et al. Neoadjuvant treatment of postmenopausal breast cancer with anastrozole, tamoxifen, or both in combination: the Immediate Preoperative Anastrozole, Tamoxifen, or Combined with Tamoxifen (IMPACT) multicenter double-blind randomized trial. J Clin Oncol 2005; 23: 5108-5116.
69. Cataliotti L, Buzdar AU, Noguchi S. et al. Comparison of anastrozole versus tamoxifen as preoperative therapy in postmenopausal women with hormone receptor-positive breast cancer-the Pre-Operative "Arimidex" Compared to Tamoxilen (PROAC7) trial. Cancer 2006; 106: 2095-2103.
70. Eiermann W, Paepke S, Appfelstaedt J. et al. Preoperative treatment of postmenopausal breast cancer patients with letrozole: a randomized doubleblind multicenter study. Ann Oncol 2001; 12: 1527-1532.
71. Semiglazov V, Kletsel A, Semiglazov V. et al. Exemestane (E) vs tamoxifen (T) as neoadjuvant endocrine therapy for postmenopausal women with ER+ breast cancer (T2N1-2, T3N0-1, T4N0M0). J Clin Oncol 2005; 23(16S): 11s (Abstr 530).
72. Jones AL, Powles TJ, Law M. et al. Adjuvant aminoglutethimide for postmenopausal patients with primary breast cancer: analysis at 8 years. J Clin Oncol 1992; 10: 1547-1552.
73. Baum M, Buzdar AU, Cuzick J. et al. Anastrozole alone or in combination with tamoxifen versus tamoxifen alone for adjuvant treatment of postmenopausal women with early breast cancer: first results of the ATAC randomised trial. Lancet 2002; 359: 2131-2139.
74. Howell A, Cuzick J, Baum M. et al. Results of the ATAC (Arimidex, Tamoxifen, Alone or in Combination) trial after completion of 5 years' adjuvant treatment for breast cancer. Lancet 2005; 365: 60-62.
75. Forbes JF, Cuzick J, Buzdar A. et al. Effect of anastrozole and tamoxifen as adjuvant treatment for early-stage breast cancer: 100-month analysis of the ATAC trial. Lancet Oncol 2008; 9: 45-53.
76. Thurlimann B, Keshaviah A, Coates AS. et al. A comparison of letrozole and tamoxifen in postmenopausal women with early breast cancer. N Engl J Med 2005; 353: 2747-2757.
77. Coates AS, Keshaviah A, Thurlimann B. et al. Five years of letrozole compared with tamoxifen as initial adjuvant therapy for postmenopausal women with endocrine-responsive early breast cancer: update of study BIG 1-98. J Clin Oncol 2007; 25: 486-492.
78. Mouridsen H, Giobbie-Hurder A, Goldhirsch A. et al. Letrozole therapy alone or in sequence with tamoxifen in women with breast cancer. N Engl J Med 2009; 361: 766-776.
79. Jones SE, Seynaeve C, Hasenburg A. et al. Results of the first planned analysis of the TEAM (tamoxifen exemestane adjuvant multinational) prospective randomized phase III trial in hormone sensitive postmenopausal early breast cancer. Cancer Res 2009; 69 (Suppl 2): 67s (Abstr 15).
80. Boccardo F, Rubagotti A, Puntoni M. et al. Switching to anastrozole versus continued tamoxifen treatment of early breast cancer: preliminary results of the Italian Tamoxifen Anastrozole trial. J Clin Oncol 2005; 23: 5138-5147.
81. Jakesz R, Jonat W, Gnant M. et al. Switching of postmenopausal women with endocrine-responsive early breast cancer to anastrozole after 2 years' adjuvant tamoxifen: combined results of ABCSG trial 8 and ARNO 95 trial. Lancet 2005; 366: 455-462.
82. Coombes RC, Hall E, Gibson LJ. et al. A randomized trial of exemestane after two to three years of tamoxifen therapy in postmenopausal women with primary breast cancer. N Engl J Med 2004; 350: 1081-1092.
83. Coombes RC, Kilburn LS, Snowdon CF. et al. Survival and safety of exemestane versus tamoxifen after 2-3 years' tamoxifen treatment (Intergroup Exemestane Study): a randomised controlled trial. Lancet 2007; 369: 559-570.
84. Goss PE, Ingle JN, Martino S. et al. Randomized trial of letrozole following tamoxifen as extended adjuvant therapy in receptor-positive breast cancer: updated findings from NCICCTG MA.17. J Natl Cancer Inst 2005; 97: 1262-1271.
85. Jakesz R, Greil R, Gnant M. et al. Extended adjuvant therapy with anastrozole among postmenopausal breast cancer patients: results from the randomized Austrian Breast and Colorectal Cancer Study Group Trial 6a. J Natl Cancer Inst 2007; 99: 1845-1853.
86. Mamounas EP, Jeong JH, Wickerham DL. et al. Benefit from exemestane as extended adjuvant therapy after 5 years of adjuvant tamoxifen: intention-totreat analysis of the National Surgical Adjuvant Breast and Bowel Project B-33 trial. J Clin Oncol 2008; 26: 1965-1971.
87. Smith IE, Harris AL, Morgan M. et al. Tamoxifen versus aminoglutethimide versus combined tamoxifen and aminoglutethimide in the treatment of advanced breast carcinoma. Cancer Res 1982; 42 (8 Suppl): 3430s-3433s.
88. Corkery J, Leonard RC, Henderson IC. et al. Tamoxifen and aminoglutethimide in advanced breast cancer. Cancer Res 1982; 42 (8 Suppl): 3409s-3414s.
89. Milsted R, Habeshaw T, Kaye S. et al. A randomised trial of tamoxifen versus tamoxifen with aminoglutethimide in post-menopausal women with advanced breast cancer. Cancer Chemother Pharmacol 1985; 14: 272-273.
90. Ingle JN, Green SJ, Ahmann DL. et al. Randomized trial of tamoxifen alone or combined with aminoglutethimide and hydrocortisone in women with metastatic breast cancer. J Clin Oncol 1986; 4: 958-964.
91. Alonso-Muñoz MC, Ojeda-Gonzalez MB, Beltran-Fabregat M. et al. Randomized trial of tamoxifen versus aminoglutethimide and versus combined tamoxifen and aminoglutethimide in advanced postmenopausal breast cancer. Oncology 1988; 45: 350-353.
92. Boccardo F, Rubagotti A, Amoroso D. et al. Sequential tamoxifen and aminoglutethimide versus tamoxifen alone in the adjuvant treatment of postmenopausal breast cancer patients: results of an Italian cooperative study. J Clin Oncol 2001; 19: 4209-4215.
93. Jonat W, Gnant M, Boccardo F. et al. Effectiveness of switching from adjuvant tamoxifen to anastrozole in postmenopausal women with hormone sensitive early-stage breast cancer: a meta-analysis. Lancet Oncol 2006; 7: 991-996.
94. Pocock SJ. The simplest statistical test: how to check for a difference between treatments. BMJ 2006; 332: 1256-1258.
95. Goss PE, Ingle JN, Martino S. et al. A randomized trial of letrozole in postmenopausal women after five years of tamoxifen therapy for early-stage breast cancer. N Engl J Med 2003; 349: 1793-1802.
96. Rea D, Hasenburg A, Seynaeve C. et al. Five years of exemestane as initial therapy compared to 5 years of tamoxifen followed by exemestane: the TEAM trial, a prospective, randomized, phase III trial in postmenopausal women with hormone-sensitive early breast cancer. Presented at: San Antonio Breast Cancer Symposium (Abstr 11). San Antonio, TX 2009.
97. Cuzick J, Sasieni P, Howell A. Should aromatase inhibitors be used as initial adjuvant treatment or sequenced after tamoxifen? Br J Cancer 2006; 94: 460-464.
98. Ellis MJ, Coop A, Singh B. et al. Letrozole is more effective neoadjuvant endocrine therapy than tamoxifen for ErbB-1- and/or ErbB-2-positive, estrogen receptor-positive primary breast cancer: evidence from a phase III randomized trial. J Clin Oncol 2001; 19: 3808-3816.
99. Dowsett M, Cuzick J, Ingle J. et al. Meta-analysis of breast cancer outcomes in adjuvant trials of aromatase inhibitors versus tamoxifen. J Clin Oncol 2010; 28: 509-518.
100. Kanis JA, Johnell O, De Laet C. et al. International variation in hip fracture probabilities: implications for risk assessment. J Bone Miner Res 2002; 17: 1237-1244.
101. Johnell O, Kanis JA, Oden A. et al. Mortality after osteoporotic fractures. Osteoporos Int 2004; 15: 38-42.
102. Coleman R, Banks L, Girgis S. et al. Skeletal effects of exemestane on bonemineral density bone biomarkers and fracture incidence in postmenopausal women with early breast cancer participating in the Intergroup Exemestane Study (IES): a randomised controlled study. Lancet Oncol 2007; 8: 119-127.
103. Eastell R, Adams JE, Coleman RE. et al. 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: 1051-1058.
104. Powles TJ, Hickish T, Kanis JA. et al. Effect of tamoxifen on bone mineral density measured by dual-energy X-ray absorptiometry in healthy premenopausal and postmenopausal women. J Clin Oncol 1996; 14: 78-84.
105. Lønning PE, Geisler J, Krag LE. et al. Effects of exemestane administered for 2 years versus placebo on bone mineral density, bone biomarkers, and plasma lipids in patients with surgically resected early breast cancer. J Clin Oncol 2005; 23: 5126-5137.
106. Perez EA, Jesse RG, Pritchard KI. et al. Effect of letrozole versus placebo on bone mineral density in women with primary breast cancer completing 5 or more years of adjuvant tamoxifen: a companion study to NCICCTG MA.17. J Clin Oncol 2006; 24: 3629-3635.
107. Geisler J, Lonning PE, Krag LE. et al. Changes in bone and lipid metabolism in postmenopausal women with early breast cancer after terminating 2-year treatment with exemestane: a randomised, placebo-controlled study. Eur J Cancer 2006; 42: 2968-2975.
108. Gnant M, Mlineritsch B, Luschin-Ebengreuth G. et al. Adjuvant endocrine therapy plus zoledronic acid in premenopausal women with early-stage breast cancer: 5-year follow-up of the ABCSG-12 bone-mineral density substudy. Lancet Oncol 2008; 9: 840-849.
109. Brufsky A, Bundred N, Coleman R. et al. Integrated analysis of zoledronic acid for prevention of aromatase inhibitor-associated bone loss in postmenopausal women with early breast cancer receiving adjuvant letrozole. Oncologist 2008; 13: 503-514.
110. Anker G, Lønning PE, Ueland PM. et al. Plasma levels of the atherogenic amino acid homocysteine in post-menopausal women with breast cancer treated with tamoxifen. Int J Cancer 1995; 60: 365-368.
111. Bonaa KH, Njolstad I, Ueland PM. et al. Homocysteine lowering and cardiovascular events after acute myocardial infarction. N Engl J Med 2006; 354: 1578-1588.
112. Anderson GL, Limacher M, Assaf AR. et al. Effects of conjugated, equine estrogen in postmenopausal women with hysterectomy-the women's health initiative randomized controlled trial. JAMA 2004; 291: 1701-1712.
113. Manson JE, Hsia J, Johnson KC. et al. Estrogen plus progestin and the risk of coronary heart disease. N Engl J Med 2003; 349: 523-534.
114. 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: 199-208.
115. Hulley S, Grady D, Bush T. et al. Randomized trial of estrogen plus progestin for secondary prevention of coronary heart disease in postmenopausal women. J Am Med Assoc 1998; 280: 605-613.
116. Alexander KP, Newby LK, Hellkamp AS. et al. Initiation of hormone replacement therapy after acute myocardial infarction is associated with more cardiac events during follow-up. J Am Coll Cardiol 2001; 38: 1-7.
117. Helle SI, Holly JM, Tally M. et al. Influence of treatment with tamoxifen and change in tumor burden on the IGF-system in breast cancer patients. Int J Cancer 1996; 69: 335-339.
118. Lønning PE, Geisler J. Indications and limitations of third-gene ration aromatase inhibitors. Expert Opin Investig Drugs 2008; 17: 723-739.
119. Wasan KM, Goss PE, Pritchard PH. et al. The influence of letrozole on serum lipid concentrations in postmenopausal women with primary breast cancer who have completed 5 years of adjuvant tamoxifen (NCIC CTG MA.17L). Ann Oncol 2005; 16: 707-715.
120. Partridge AH, LaFountain A, Mayer E. et al. Adherence to initial adjuvant anastrozole therapy among women with early-stage breast cancer. J Clin Oncol 2008; 26: 556-562.
121. Dent S, Hopkins S, Di Valentin T. et al. Adjuvant aromatase inhibitors in early breast cancer-toxicity and adherence. Important observations in clinical practice. Breast Cancer Res Treat 2007; 106 (Suppl 1): S111 (Abstr 2079).
122. Morales L, Pans S, Verschueren K. et al. Prospective study to assess short-term intra-articular and tenosynovial changes in the aromatase inhibitor-associated arthralgia syndrome. J Clin Oncol 2008; 26: 3147-3152.
123. Renshaw L, McHugh M, Williams L. et al. Comparison of joint problems as reported by patients in a randomised adjuvant trial of anastrozole and letrozole. Breast Cancer Res Treat 2007; 106 (Suppl 1): S108 (Abstr 2072).
124. Stewart HJ, Prescott RJ, Forrest APM. Scottish adjuvant tamoxifen trial: a randomized study updated to 15 years. J Natl Cancer Inst 2001; 93: 456-462.
125. Masamura S, Santner SJ, Heitjan DF, Santen RJ. Estrogen deprivation causes estradiol hypersensitivity in human breast cancer cells. J Clin Endocrinol Metab 1995; 80: 2918-2925.
126. Martin LA, Farmer I, Johnston SR. Enhanced estrogen receptor (ER) alpha, ERBB2, and MAPK signal transduction pathways operate during the adaptation of MCF-7 cells to long term estrogen deprivation. J Biol Chem 2003; 278: 30458-30468.
127. Lønning PE, Taylor PD, Anker G. et al. High-dose estrogen treatment in postmenopausal breast cancer patients heavily exposed to endocrine therapy. Breast Cancer Res Treat 2001; 67: 111-116.
128. Lønning PE. Stepwise estrogen suppression manipulating the estrostat. J Steroid Biochem Mol Biol 2001; 79: 127-132.
129. Lewis-Wambi JS, Jordan VC. Estrogen regulation of apoptosis: how can one hormone stimulate and inhibit? Breast Cancer Res 2009; 11: 206.
130. Jordan VC. The 38th David A. Karnofsky lecture: the paradoxical actions of estrogen in breast cancer-survival or death? J Clin Oncol 2008; 26: 3073-3082.
131. Rose C, Vtoraya O, Pluzanska A. et al. An open randomised trial of second-line endocrine therapy in advanced breast cancer: comparison of the aromatase inhibitors letrozole and anastrozole. Eur J Cancer 2003; 39: 2318-2327.
132. Mouridsen H, Gershanovich M, Sun Y. et al. Superior efficacy of letrozole versus tamoxifen as first-line therapy for postmenopausal women with advanced breast cancer: results of a phase III study of the International Letrozole Breast Cancer Group. J Clin Oncol 2001; 19: 2596-2606.
133. Nabholtz JM, Buzdar A, Pollak M. et al. Anastrozole is superior to tamoxifen as firstline therapy for advanced breast cancer in postmenopausal women: results of a North American multicenter randomized trial. J Clin Oncol 2000; 18: 3758-3767.
134. Bonneterre J, Thurlimann B, Robertson JFR. et al. Anastrozole versus tamoxifen as first-line therapy for advanced breast cancer in 668 postmenopausal women: results of the tamoxifen or arimidex randomized group efficacy and tolerability study. J Clin Oncol 2000; 18: 3748-3757.
135. Milla-Santos A, Milla L, Portella J. et al. Anastrozole versus tamoxifen as firstline therapy in postmenopausal patients with hormone-dependent advanced breast cancer-a prospective, randomized, phase III study. Am J Clin Oncol 2003; 26: 317-322.
136. Lønning PE. Lack of complete cross-resistance between different aromatase inhibitors; a real finding in search for an explanation? Eur J Cancer 2009; 45: 527-535.
137. Chia S, Gradishar W, Mauriac L. et al. Double-blind, randomized placebo controlled trial of fulvestrant compared with exemestane after prior nonsteroidal aromatase inhibitor therapy in postmenopausal women with hormone receptorpositive, advanced breast cancer: results from EFECT. J Clin Oncol 2008; 26: 1664-1670.