The what, why and how of aromatase inhibitors: Hormonal agents for treatment and prevention of breast cancer

International Journal of Clinical Practice

Volumn 61, Issue 12, 2007, Pages 2051-2063

  Fabian, C J ^a,b  

^a UNIVERSITY OF KANSAS SCHOOL OF MEDICINE   (United States)

^b UNIVERSITY OF KANSAS MEDICAL CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AMINOGLUTETHIMIDE; ANASTROZOLE; AROMATASE INHIBITOR; BISPHOSPHONIC ACID DERIVATIVE; CELECOXIB; CLONIDINE; COLECALCIFEROL; ESTRADIOL; ESTRIOL; ESTROGEN; EXEMESTANE; FADROZOLE; FLUOXETINE; FULVESTRANT; GABAPENTIN; GESTAGEN; GONADORELIN DERIVATIVE; GOSERELIN; HORMONE RECEPTOR; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; LETROZOLE; PLACEBO; RALOXIFENE; SEROTONIN UPTAKE INHIBITOR; TAMOXIFEN; TESTOSTERONE; UNINDEXED DRUG; VENLAFAXINE; VOROZOLE; ZOLEDRONIC ACID;

ALOPECIA; ARTHRALGIA; ATAXIA; BONE ATROPHY; BREAST CANCER; CANCER ADJUVANT THERAPY; CANCER COMBINATION CHEMOTHERAPY; CANCER HORMONE THERAPY; CANCER PATIENT; CANCER PREVENTION; CANCER RISK; CARDIOVASCULAR DISEASE; CHEMOTHERAPY INDUCED EMESIS; CLINICAL TRIAL; COMBINATION CHEMOTHERAPY; DEEP VEIN THROMBOSIS; DIZZINESS; DROWSINESS; DRUG ACTIVITY; DRUG APPROVAL; DRUG ERUPTION; DRUG FATALITY; DRUG MECHANISM; DRUG SUBSTITUTION; DRUG USE; DYSPAREUNIA; DYSPEPSIA; ENDOMETRIUM CANCER; FATIGUE; FRACTURE; HEART DEATH; HEART MUSCLE ISCHEMIA; HIGH RISK PATIENT; HOT FLUSH; HUMAN; ISCHEMIC HEART DISEASE; JOINT STIFFNESS; LIBIDO DISORDER; LUNG EMBOLISM; MENOPAUSAL SYNDROME; METASTASIS; MONOTHERAPY; MYALGIA; NAUSEA; NONHUMAN; OSTEOLYSIS; OSTEOPOROSIS; PAIN; PHYSICIAN; POSTMENOPAUSE; PREMENOPAUSE; PRIMARY PREVENTION; PRIORITY JOURNAL; REVIEW; SIDE EFFECT; THROMBOEMBOLISM; UNSPECIFIED SIDE EFFECT; UTERUS CANCER; VAGINA BLEEDING; VAGINAL DRYNESS; VASOMOTOR DISORDER; VITAMIN SUPPLEMENTATION; XEROSTOMIA;

ANDROSTADIENES; AROMATASE INHIBITORS; BREAST NEOPLASMS; CARDIOVASCULAR DISEASES; CHEMOTHERAPY, ADJUVANT; DRUG RESISTANCE; FEMALE; HUMANS; MUSCULOSKELETAL DISEASES; NITRILES; POSTMENOPAUSE; PREMENOPAUSE; TAMOXIFEN; THROMBOEMBOLISM; TRIAZOLES;

EID: 35948931718     PISSN: 13685031     EISSN: 17421241     Source Type: Journal    
DOI: 10.1111/j.1742-1241.2007.01587.x     Document Type: Review

References (104)

1. Fabian CJ, Kimler BF. Selective estrogen-receptor modulators for primary prevention of breast cancer. J Clin Oncol 2005 23 : 1644 55.
2. Simpson ER, Davis SR. Minireview: aromatase and the regulation of estrogen biosynthesis-some new perspectives. Endocrinology 2001 142 : 4589 94.
3. 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 7.
4. Dowsett M, Stein RC, Mehta A, Coombes RC. Potency and selectivity of the non-steroidal aromatase inhibitor CGS 16949A in postmenopausal breast cancer patients. Clin Endocrinol (Oxf) 1990 32 : 623 34.
5. van der Wall E, Donker TH, de Frankrijker E et al. Inhibition of the in vivo conversion of androstenedione to estrone by the aromatase inhibitor vorozole in healthy postmenopausal women. Cancer Res 1993 53 : 4563 6.
6. Dowsett M, Jones A, Johnston SR et al. In vivo measurement of aromatase inhibition by letrozole (CGS 20267) in postmenopausal patients with breast cancer. Clin Cancer Res 1995 1 : 1511 5.
7. Geisler J, King N, Dowsett M et al. Influence of anastrozole (Arimidex), 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 91.
8. 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 93.
9. Winer EP. Optimizing endocrine therapy for breast cancer. J Clin Oncol 2005 23 : 1609 10.
10. Early Breast Cancer Trialists' Collaborative Group (EBCTCG). Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials. Lancet 2005 365 : 1687 717.
11. Hu JC, Mokbel K. Does c-erbB2/HER2 overexpression predict adjuvant tamoxifen failure in patients with early breast cancer? Eur J Surg Oncol 2001 27 : 335 7.
12. Osborne CK, Bardou V, Hopp TA et al. Role of the estrogen receptor coactivator AIB1 (SRC-3) and HER-2/neu in tamoxifen resistance in breast cancer. J Natl Cancer Inst 2003 95 : 353 61.
13. Fisher B, Dignam J, Bryant J, Wolmark N. Five versus more than five years of tamoxifen for lymph node-negative breast cancer: updated findings from the National Surgical Adjuvant Breast and Bowel Project B-14 randomized trial. J Natl Cancer Inst 2001 93 : 684 90.
14. Dowsett M, Martin LA, Smith I, Johnston S. Mechanisms of resistance to aromatase inhibitors. J Steroid Biochem Mol Biol 2005 95 : 167 72.
15. Ellis MJ, Coop A, Singh B et al. Letrozole inhibits tumor proliferation more effectively than tamoxifen independent of HER1/2 expression status. Cancer Res 2003 63 : 6523 31.
16. Ingle JN, Suman VJ. Aromatase inhibitors for therapy of advanced breast cancer. J Steroid Biochem Mol Biol 2005 95 : 113 9.
17. Gibson LJ, Dawson CK, Lawrence DH, Bliss JM. Aromatase inhibitors for treatment of advanced breast cancer in postmenopausal women. Cochrane Database Syst Rev 2007 CD003370.
18. Winer EP, Hudis C, Burstein HJ et al. American Society of Clinical Oncology technology assessment on the use of aromatase inhibitors as adjuvant therapy for postmenopausal women with hormone receptor-positive breast cancer: Status Report 2004. J Clin Oncol 2005 23 : 619 29.
19. Carey LA, Metzger R, Dees EC et al. American Joint Committee on Cancer tumor-node-metastasis stage after neoadjuvant chemotherapy and breast cancer outcome. J Natl Cancer Inst 2005 97 : 1137 42.
20. Eiermann W, Paepke S, Appfelstaedt J et al. Preoperative treatment of postmenopausal breast cancer patients with letrozole: a randomized double-blind multicenter trial. Ann Oncol 2001 12 : 1527 32.
21. 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 16.
22. Semiglazov VF, Semiglazov V, Ivanov V et al. The relative efficacy of neoadjuvant endocrine therapy vs chemotherapy in postmenopausal women with ER- positive breast cancer. J Clin Oncol 2004 22 : 519.
23. 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 16.
24. 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 2.
25. Buzdar AU, Guastalla JP, Nabholtz JM et al. Impact of chemotherapy regimens prior to endocrine therapy: Results from the ATAC (Anastrozole and Tamoxifen, Alone or in Combination) trial. Cancer 2006 107 : 472 80.
26. 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 57.
27. 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 92.
28. 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 802.
29. 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 NCIC CTG MA.17. J Natl Cancer Inst 2005 97 : 1262 71.
30. Whelan TJ, Goss PE, Ingle JN et al. Assessment of quality of life in MA.17: a randomized, placebo-controlled trial of letrozole after 5 years of tamoxifen in postmenopausal women. J Clin Oncol 2005 23 : 6931 40.
31. 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 92.
32. Coombes R, Kilburn L, Snowdon C 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 70.
33. Fallowfield LJ, Bliss JM, Porter LS et al. Quality of life in the Intergroup Exemestane Study: a randomized trial of exemestane versus continued tamoxifen after 2 to 3 years of tamoxifen in postmenopausal women with primary breast cancer. J Clin Oncol 2006 24 : 910 7.
34. 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 47.
35. Kaufmann M, Jonat W, Hilfrich J et al. Survival benefit of switching to anastrozole after 2 years' treatment with tamoxifen versus continued tamoxifen therapy: the ARNO 95 Study. J Clin Oncol 2006 24 : 547.
36. Forward DP, Cheung KL, Jackson L, Robertson JF. Clinical and endocrine data for goserelin plus anastrozole as second-line endocrine therapy for premenopausal advanced breast cancer. Br J Cancer 2004 90 : 590 4.
37. Carlson R. Goserelin plus anastrozole for treatment of premenopausal women with hormone receptor positive recurrent/metastatic breast cancer [Abstract]. Breast Cancer Res Treat 2004 88 : S237 8.
38. Fallowfield L, Cella D, Cuzick J et al. Quality of life of postmenopausal women in the Arimidex, Tamoxifen, Alone or in Combination (ATAC) Adjuvant Breast Cancer Trial. J Clin Oncol 2004 22 : 4261 71.
39. Howell A, Cuzick J. Vascular effects of aromatase inhibitors: data from clinical trials. J Steroid Biochem Mol Biol 2005 95 : 143 9.
40. Morales L, Neven P, Timmerman D et al. Acute effects of tamoxifen and third-generation aromatase inhibitors on menopausal symptoms of breast cancer patients. Anticancer Drugs 2004 15 : 753 60.
41. Ward RL, Morgan G, Dalley D, Kelly PJ. Tamoxifen reduces bone turnover and prevents lumbar spine and proximal femoral bone loss in early postmenopausal women. Bone Miner 1993 22 : 87 94.
42. Lonning 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 37.
43. Perez EA, Josse 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 NCIC CTG MA.17. J Clin Oncol 2006 24 : 3629 35.
44. Coleman R, Banks L, Girgis S et al. Skeletal effect of exemestane in the Intergroup Exemestane Study (IES) 2 year bone mineral density (BMD) and bone biomarker data [abstract 5076]. Breast Cancer Res Treat 2005 94 : S233.
45. Chapurlat RD, Garnero P, Breart G et al. Serum estradiol and sex hormone-binding globulin and the risk of hip fracture in elderly women: the EPIDOS study. J Bone Miner Res 2000 15 : 1835 41.
46. McCloskey E, Hannon R, Lakner G et al. The letrozole (L), exemestane (E), and anastrozole (A) pharmacodynamics (LEAP) trial: a direct comparison of bone biochemical measurements between aromatase inhibitors (AIs) in healthy postmenopausal women. J Clin Oncol 2006 24 : 555.
47. Chien AJ, Goss PE. Aromatase inhibitors and bone health in women with breast cancer. J Clin Oncol 2006 24 : 5305 12.
48. Baum M, Buzdar A, Cuzick J et al. Anastrozole alone or in combination with tamoxifen versus tamoxifen alone for adjuvant treatment of postmenopausal women with early-stage breast cancer: results of the ATAC (Arimidex, Tamoxifen Alone or in Combination) trial efficacy and safety update analyses. Cancer 2003 98 : 1802 10.
49. Gnant MF, Mlineritsch B, Luschin-Ebengreuth G et al. Zoledronic acid prevents cancer treatment-induced bone loss in premenopausal women receiving adjuvant endocrine therapy for hormone-responsive breast cancer: a report from the Austrian Breast and Colorectal Cancer Study Group. J Clin Oncol 2007 25 : 820 8.
50. Brufsky A. Management of cancer-treatment-induced bone loss in postmenopausal women undergoing adjuvant breast cancer therapy: a Z-FAST update. Semin Oncol 2006 33 : S13 7.
51. 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 75.
52. Taylor M, Rastelli A, Civitelli R, Ellis M. Incidence of 25-OH vitamin D deficiency in patients with a history of breast cancer who have musculoskeletal symptomatology [Abstract]. Breast Cancer Res Treat 2004 88 : S137.
53. Garland CF, Garland FC, Gorham ED et al. The role of vitamin D in cancer prevention. Am J Public Health 2006 96 : 252 61.
54. Heaney RP, Davies KM, Chen TC, Holick MF, Barger-Lux MJ. Human serum 25-hydroxycholecalciferol response to extended oral dosing with cholecalciferol. Am J Clin Nutr 2003 77 : 204 10.
55. Heaney RP. Vitamin D requirement in health and disease. J Steroid Biochem Mol Biol 2005 97 : 13 9.
56. Freyer G, Debled M, Geay JF et al. Celecoxib (Ce) + exemestane (Ex) versus placebo + Ex in post-menopausal (PM) metastatic breast cancer (MBC) patients (pts): a double-blind phase III GINECO study. J Clin Oncol 2006 24 : 565.
57. Atalay G, Dirix L, Biganzoli L et al. The effect of exemestane on serum lipid profile in postmenopausal women with metastatic breast cancer: a companion study to EORTC Trial 10951, 'Randomized phase II study in first line hormonal treatment for metastatic breast cancer with exemestane or tamoxifen in postmenopausal patients'. Ann Oncol 2004 15 : 211 7.
58. Bundred NJ. The effects of aromatase inhibitors on lipids and thrombosis. Br J Cancer 2005 93 : S23 7.
59. Stamatelopoulos KS, Lekakis JP, Poulakaki NA et al. Tamoxifen improves endothelial function and reduces carotid intima-media thickness in postmenopausal women. Am Heart J 2004 147 : 1093 9.
60. Braithwaite RS, Chlebowski RT, Lau J et al. Meta-analysis of vascular and neoplastic events associated with tamoxifen. J Gen Intern Med 2003 18 : 937 47.
61. Barrett-Connor E, Mosca L, Collins P et al. Effects of raloxifene on cardiovascular events and breast cancer in postmenopausal women. N Engl J Med 2006 355 : 125 37.
62. Blumenthal RS, Baranowski B, Dowsett SA. Cardiovascular effects of raloxifene: the arterial and venous systems. Am Heart J 2004 147 : 783 9.
63. Chlebowski RT, Kim JA, Col NF. Estrogen deficiency symptom management in breast cancer survivors in the changing context of menopausal hormone therapy. Semin Oncol 2003 30 : 776 88.
64. Kendall A, Dowsett M, Folkerd E, Smith I. Caution: vaginal estradiol appears to be contraindicated in postmenopausal women on adjuvant aromatase inhibitors. Ann Oncol 2006 17 : 584 7.
65. Bachmann GA, Leiblum SR. The impact of hormones on menopausal sexuality: a literature review. Menopause 2004 11 : 120 30.
66. Somboonporn W, Davis SR. Testosterone effects on the breast: implications for testosterone therapy for women. Endocr Rev 2004 25 : 374 88.
67. Fisher B, Costantino JP, Wickerham DL et al. Tamoxifen for prevention of breast cancer: report of the National Surgical Adjuvant Breast and Bowel Project P-1 Study. J Natl Cancer Inst 1998 90 : 1371 88.
68. Cuzick J, Forbes JF, Sestak I et al. Long-term results of tamoxifen prophylaxis for breast cancer - 96-month follow-up of the randomized IBIS-I trial. J Natl Cancer Inst 2007 99 : 272 82.
69. Veronesi U, Maisonneuve P, Rotmensz N et al. Tamoxifen for the prevention of breast cancer: late results of the Italian Randomized Tamoxifen Prevention Trial among women with hysterectomy. J Natl Cancer Inst 2007 99 : 727 37.
70. Powles TJ, Ashley S, Tidy A, Smith IE, Dowsett M. Twenty-year follow-up of the Royal Marsden randomized, double-blinded tamoxifen breast cancer prevention trial. J Natl Cancer Inst 2007 99 : 283 90.
71. Lonning P, Geisler J, Krag LE et al. Vitamin D deficiency: a threat to bone health in breast cancer patients during adjuvant treatment with aromatase inhibitors. J Clin Oncol 2006 24 (18S 554.
72. Lappe JM, Travers-Gustafson D, Davies KM, Recker RR, Heaney RP. Vitamin D and calcium supplementation reduces cancer risk: results of a randomized trial. Am J Clin Nutr 2007 85 : 1586 91.
73. Hillner BE, Ingle JN, Chlebowski RT et al. American Society of Clinical Oncology 2003 update on the role of bisphosphonates and bone health issues in women with breast cancer. J Clin Oncol 2003 21 : 4042 57.
74. Brufsky A, Bundred N, Coleman R et al. An integrated analysis of zoledronic acid (ZA) for prevention of aromatase inhibitor associated bone loss (AIBL) in postmenopausal women (PMW) with early breast cancer (BCa) receiving adjuvant letrozole (LET). Breast Cancer Res Treat 2006 100 (Suppl. 1 S25 (abstract 107).
75. Kendall A, Smith I, Folkerd E, Dowsett M. Aromatase inhibition and very low dose estradiol add-back: a pilot study for novel breast cancer prevention [Abstract]. J Clin Oncol 2006 24 : 1014.
76. Campbell MJ, Esserman LJ, Zhou Y et al. Breast cancer growth prevention by statins. Cancer Res 2006 66 : 8707 14.
77. Eliassen AH, Colditz GA, Rosner B et al. Serum lipids, lipid-lowering drugs, and the risk of breast cancer. Arch Intern Med 2005 165 : 2264 71.
78. Kumar AS, Esserman LJ. Statins: health-promoting agents show promise for breast cancer prevention. Clin Breast Cancer 2005 6 : 455 9.
79. Bonovas S, Filioussi K, Tsavaris N, Sitaras NM. Use of statins and breast cancer: a meta-analysis of seven randomized clinical trials and nine observational studies. J Clin Oncol 2005 23 : 8606 12.
80. National Institutes of Health. National Institutes of Health State-of-the-Science Conference statement: management of menopause-related symptoms. Ann Intern Med 2005 142 : 1003 13.
81. Nelson HD. Commonly used types of postmenopausal estrogen for treatment of hot flashes: scientific review. JAMA 2004 291 : 1610 20.
82. Rossouw JE, Anderson GL, Prentice RL et al. 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 : 321 33.
83. 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 12.
84. Rossouw JE, Prentice RL, Manson JE et al. Postmenopausal hormone therapy and risk of cardiovascular disease by age and years since menopause. JAMA 2007 297 : 1465 77.
85. Stefanick ML, Anderson GL, Margolis KL et al. Effects of conjugated equine estrogens on breast cancer and mammography screening in postmenopausal women with hysterectomy. JAMA 2006 295 : 1647 57.
86. Beral V. Breast cancer and hormone-replacement therapy in the Million Women Study. Lancet 2003 362 : 419 27.
87. Vogel VG. Reducing the risk of breast cancer with tamoxifen in women at increased risk. J Clin Oncol 2001 19 : 87S 92.
88. Tekmal RR, Liu YG, Nair HB et al. Estrogen receptor alpha is required for mammary development and the induction of mammary hyperplasia and epigenetic alterations in the aromatase transgenic mice. J Steroid Biochem Mol Biol 2005 95 : 9 15.
89. Ernster VL, Wrensch MR, Petrakis NL et al. Benign and malignant breast disease: initial study results of serum and breast fluid analyses of endogenous estrogens. J Natl Cancer Inst 1987 79 : 949 60.
90. Santen RJ, Martel J, Hoagland M et al. Demonstration of aromatase activity and its regulation in breast tumor and benign breast fibroblasts. Breast Cancer Res Treat 1998 49 (Suppl. 1 S93 9 discussion S109 19.
91. Fabian CJ, Kimler BF, Zalles CM et al. Reduction in proliferation with six months of letrozole in women on hormone replacement therapy. Breast Cancer Res Treat 2007 doi:.
92. Jordan VC. SERMs: meeting the promise of multifunctional medicines. J Natl Cancer Inst 2007 99 : 350 6.
93. Brodie A, Sabnis G, Macedo L. Xenograft models for aromatase inhibitor studies. J Steroid Biochem Mol Biol 2007 doi:.
94. Robertson JF, Osborne CK, Howell A et al. Fulvestrant versus anastrozole for the treatment of advanced breast carcinoma in postmenopausal women: a prospective combined analysis of two multicenter trials. Cancer 2003 98 : 229 38.
95. 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 : 5439 44.
96. 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 6.
97. Lewis JS, Meeke K, Osipo C et al. Intrinsic mechanism of estradiol-induced apoptosis in breast cancer cells resistant to estrogen deprivation. J Natl Cancer Inst 2005 97 : 1746 59.
98. Marcom PK, Isaacs C, Harris L et al. The combination of letrozole and trastuzumab as first or second-line biological therapy produces durable responses in a subset of HER2 positive and ER positive advanced breast cancers. Breast Cancer Res Treat 2007 102 : 43 9.
99. Lane HA, Lebwohl D. Future directions in the treatment of hormone-sensitive advanced breast cancer: the RAD001 (Everolimus)-letrozole clinical program. Semin Oncol 2006 33 (2 Suppl. 7 S18 25.
100. Brueggemeier RW, Hackett JC, Diaz-Cruz ES. Aromatase inhibitors in the treatment of breast cancer. Endocr Rev 2005 26 : 331 45.
101. FEMARA® (Letrozole Tablets). Full Prescribing Information. East Hanover, NJ : Novartis Pharmaceuticals Corporation, 2005.
102. ARIMIDEX® (Anastrozole Tablets). Full Prescribing Information. Wilmington, DE : AstraZeneca Pharmaceuticals LP, 2005.
103. Aromasin® (Exemestane Tablets). Full Prescribing Information. New York, NY : Pharmacia & Upjohn Co., Division of Pfizer Inc., 2005.
104. Brueggemeier RW. Overview of the pharmacology of the aromatase inactivator exemestane. Breast Cancer Res Treat 2002 74 : 177 85.