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Aromatase inhibitor therapy: toxicities and management strategies in the treatment of postmenopausal women with hormone-sensitive early breast cancer

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Abstract

Aromatase inhibitors (AIs) have been shown to reduce the risk of breast cancer recurrence and are widely used today as adjuvant therapy in women with early stage endocrine-responsive breast cancer. Aromatase inhibitors may be prescribed as initial hormonal therapy, sequentially following 2–3 years of tamoxifen, or as extended adjuvant therapy (following 5 years of tamoxifen). Aromatase inhibitors are generally well tolerated; however, certain side effects, particularly arthralgia/musculoskeletal symptoms and gynecologic effects, may result in poor adherence to treatment. Patients receiving adjuvant therapy with an AI should be counseled regarding possible side effects and the importance of completing treatment. Interventions to ameliorate side effects should be individualized based on symptoms, comorbid conditions, and pre-existing therapies. In addition, bone and cardiovascular health should be monitored during AI therapy. Prompt therapeutic management of common side effects associated with AIs may provide patients with the opportunity to receive the full benefit of their adjuvant hormonal treatment while minimizing toxicity.

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References

  1. Early Breast Cancer Trialists’ Collaborative Group (EBCTCG) (2005) Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials. Lancet 365:1687–1717

    Article  Google Scholar 

  2. Lin NU, Winer EP (2008) Advances in adjuvant endocrine therapy for postmenopausal women. J Clin Oncol 26:798–805

    Article  PubMed  CAS  Google Scholar 

  3. Dowsett M, Cuzick J, Ingle J et al (2010) Meta-analysis of breast cancer outcomes in adjuvant trials of aromatase inhibitors versus tamoxifen. J Clin Oncol 28:509–518

    Article  PubMed  CAS  Google Scholar 

  4. Punglia RS, Burstein HJ, Winer EP, Weeks JC (2008) Pharmacogenomic variation of CYP2D6 and the choice of optimal adjuvant endocrine therapy for postmenopausal breast cancer: a modeling analysis. J Natl Cancer Inst 100:642–648

    Article  PubMed  CAS  Google Scholar 

  5. Leyland-Jones B, Regan MM, Bouzyk M et al (2010) Outcome according to CYP2D6 genotype among postmenopausal women with endocrine-responsive early invasive breast cancer randomized in the BIG 1–98 trial (abstr S1-8). In: 33rd Annual San Antonio Breast Cancer Symposium, San Antonio, TX

  6. Seruga B, Amir E (2010) Cytochrome P450 2D6 and outcomes of adjuvant tamoxifen therapy: results of a meta-analysis. Breast Cancer Res Treat 122:609–617

    Article  PubMed  CAS  Google Scholar 

  7. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology™ v.1.2009: Breast Cancer. http://www.nccn.org/professionals/physician_gls/PDF/breast.pdf. Accessed 11 Mar 2009

  8. Goldhirsch A, Wood WC, Gelber RD et al (2007) Progress and promise: highlights of the international expert consensus on the primary therapy of early breast cancer 2007. Ann Oncol 18:1133–1144

    Article  PubMed  CAS  Google Scholar 

  9. Winer EP, Hudis C, Burstein HJ et al (2005) 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 23:619–629

    Article  PubMed  CAS  Google Scholar 

  10. Coates AS, Keshaviah A, Thurlimann B et al (2007) 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 25:486–492

    Article  PubMed  CAS  Google Scholar 

  11. Coombes RC, Kilburn LS, Snowdon CF et al (2007) Survival and safety of exemestane versus tamoxifen after 2–3 years’ tamoxifen treatment (Intergroup Exemestane Study): a randomised controlled trial. Lancet 369:559–570

    Article  PubMed  CAS  Google Scholar 

  12. Forbes JF, Cuzick J, Buzdar A et al (2008) Effect of anastrozole and tamoxifen as adjuvant treatment for early-stage breast cancer: 100-month analysis of the ATAC trial. Lancet Oncol 9:45–53

    Article  PubMed  Google Scholar 

  13. Thurlimann B, Keshaviah A, Coates AS et al (2005) A comparison of letrozole and tamoxifen in postmenopausal women with early breast cancer. N Engl J Med 353:2747–2757

    Article  PubMed  Google Scholar 

  14. Miaskowski C, Shockney L, Chlebowski RT (2008) Adherence to oral endocrine therapy for breast cancer: a nursing perspective. Clin J Oncol Nurs 12:213–221

    Article  PubMed  Google Scholar 

  15. Presant CA, Bosserman L, Young T et al (2007) Aromatase inhibitor-associated arthralgia and/or bone pain: frequency and characterization in non-clinical trial patients. Clin Breast Cancer 7:775–778

    Article  PubMed  CAS  Google Scholar 

  16. Bramwell VH, Pritchard KI, Tu D et al (2010) A randomized placebo-controlled study of tamoxifen after adjuvant chemotherapy in premenopausal women with early breast cancer (National Cancer Institute of Canada–Clinical Trials Group Trial, MA.12). Ann Oncol 21:283–290

    Article  PubMed  CAS  Google Scholar 

  17. Bertelli G, Hall E, Ireland E et al (2010) Long-term endometrial effects in postmenopausal women with early breast cancer participating in the Intergroup Exemestane Study (IES)—a randomised controlled trial of exemestane versus continued tamoxifen after 2–3 years tamoxifen. Ann Oncol 21:498–505

    Article  PubMed  CAS  Google Scholar 

  18. Buzdar A, Howell A, Cuzick J et al (2006) Comprehensive side-effect profile of anastrozole and tamoxifen as adjuvant treatment for early-stage breast cancer: long-term safety analysis of the ATAC trial. Lancet Oncol 7:633–643

    Article  PubMed  CAS  Google Scholar 

  19. Howell A, Cuzick J, Baum M et al (2005) Results of the ATAC (Arimidex, Tamoxifen, Alone or in Combination) trial after completion of 5 years’ adjuvant treatment for breast cancer. Lancet 365:60–62

    Article  PubMed  CAS  Google Scholar 

  20. Eastell R, Adams JE, Coleman RE et al (2008) Effect of anastrozole on bone mineral density: 5-year results from the anastrozole, tamoxifen, alone or in combination trial 18233230. J Clin Oncol 26:1051–1057

    Article  PubMed  CAS  Google Scholar 

  21. Jones SE, Seynaeve C, Hasenburg A et al (2008) 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 (abstr 15). In: 31st Annual San Antonio Breast Cancer Symposium, San Antonio, TX

  22. Kaufmann M, Jonat W, Hilfrich J et al (2007) Improved overall survival in postmenopausal women with early breast cancer after anastrozole initiated after treatment with tamoxifen compared with continued tamoxifen: the ARNO 95 Study. J Clin Oncol 25:2664–2670

    Article  PubMed  CAS  Google Scholar 

  23. Jakesz R, Gnant M, Griel R et al (2008) Tamoxifen and anastrozole as a sequencing strategy in postmenopausal women with hormone-responsive early breast cancer: updated data from the Austrian breast and colorectal cancer study group trial 8 (abstr 14). In: 31st Annual San Antonio Breast Cancer Symposium, San Antonio, TX

  24. Coombes RC, Bliss JM, Hall E (2005) Safety of exemestane in the Intergroup Exemestane Study [letter]. J Clin Oncol 23:3171–3172

    Article  PubMed  Google Scholar 

  25. Coombes RC, Hall E, Gibson LJ et al (2004) A randomized trial of exemestane after two to three years of tamoxifen therapy in postmenopausal women with primary breast cancer. N Engl J Med 350:1081–1092

    Article  PubMed  CAS  Google Scholar 

  26. Coleman RE, Banks LM, Girgis LM et al (2008) Reversal of skeletal effects of endocrine treatments in the Intergroup Exemestane Study (IES) (poster 1128). In: 31st Annual San Antonio Breast Cancer Symposium, San Antonio, TX

  27. Coleman RE, Banks LM, Girgis SI et al (2007) Skeletal effects of exemestane on bone-mineral 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 8:119–127

    Article  PubMed  CAS  Google Scholar 

  28. Hadji P, Ziller M, Kieback DG et al (2009) Effects of exemestane and tamoxifen on bone health within the Tamoxifen Exemestane Adjuvant Multicentre (TEAM) trial: results of a German, 12-month, prospective, randomised substudy. Ann Oncol 20:1203–1209

    Article  PubMed  CAS  Google Scholar 

  29. Hadji P, Ziller M, Kieback DG et al (2009) The effect of exemestane or tamoxifen on markers of bone turnover: results of a German sub-study of the Tamoxifen Exemestane Adjuvant Multicentre (TEAM) trial. Breast 18:159–164

    Article  PubMed  CAS  Google Scholar 

  30. Rea D, Hasenburg A, Seynaeve C et al (2009) 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 (abstr 11). In: 32nd Annual San Antonio Breast Cancer Symposium, San Antonio, TX

  31. Mouridsen H, Giobbie-Hurder A, Goldhirsch A et al (2009) Letrozole therapy alone or in sequence with tamoxifen in women with breast cancer. N Engl J Med 361:766–776

    Article  PubMed  CAS  Google Scholar 

  32. Goss PE, Ingle JN, Martino S et al (2005) 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 97:1262–1271

    Article  PubMed  CAS  Google Scholar 

  33. Goss PE, Ingle JN, Martino S et al (2009) Outcomes of women who were premenopausal at diagnosis of early breast cancer in the NCIC CTG MA17 trial (abstr 13). In: 32nd Annual San Antonio Breast Cancer Symposium, San Antonio, TX

  34. Perez EA, Josse RG, Pritchard KI et al (2006) 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 24:3629–3635

    Article  PubMed  CAS  Google Scholar 

  35. Buzdar AU (2006) Clinical features of joint symptoms observed in the ‘Arimedex’, Tamoxifen, Alone or in Combination (ATAC) trial (abstr 551). J Clin Oncol 24:15s

    Article  Google Scholar 

  36. Ribi K, Aldridge J, Phillips K et al (2010) Changes in cognitive function in postmenopausal women 1 year after completing adjuvant letrozole or tamoxifen in the Breast International Group (BIG) 1–98 trial (abstr 527). J Clin Oncol 28:74s

    Google Scholar 

  37. Coombes RC, Kilburn LS, Beare SL, Snowdon CF, Bliss JM (2009) Survival and safety post study treatment completion: an updated analysis of the Intergroup Exemestane Study (IES) (abstr O-5010). In: Joint ECCO 15–34th ESMO Multidisciplinary Congress, Berlin, Germany

  38. Hardin JG (1990) Arthralgia. In: Walker KH, Hall WD, Hurst JW (Eds) Clinical methods, 3rd edn. Butterworth Publishers, New York

  39. Felson DT, Cummings SR (2005) Aromatase inhibitors and the syndrome of arthralgias with estrogen deprivation. Arthritis Rheum 52:2594–2598

    Article  PubMed  CAS  Google Scholar 

  40. Hadji P (2008) Menopausal symptoms and adjuvant therapy-associated adverse events. Endocr Relat Cancer 15:73–90

    Article  PubMed  CAS  Google Scholar 

  41. Crew KD, Greenlee H, Capodice J et al (2007) Prevalence of joint symptoms in postmenopausal women taking aromatase inhibitors for early-stage breast cancer. J Clin Oncol 25:3877–3883

    Article  PubMed  Google Scholar 

  42. Donnellan PP, Douglas SL, Cameron DA, Leonard RCF (2001) Aromatase inhibitors and arthralgia. J Clin Oncol 19:2767

    PubMed  CAS  Google Scholar 

  43. Yamamoto Y, Kawasoe T, Ibusuki M et al (2007) Aromatase inhibitor-induced joint symptom in patients with breast cancer. J Clin Oncol 25:11070

    Google Scholar 

  44. Yardley DA, Green NB, Papish S et al (2009) Rheumatologic evaluation of adjuvant letrozole in postmenopausal breast cancer patients discontinuing anastrozole due to grade 2-3 arthralgia or myalgia (abstr 805). In: 32nd Annual San Antonio Breast Cancer Symposium, San Antonio, TX

  45. Briot K, Tubiana-Hulin M, Bastit L, Kloos I, Roux C (2010) Effect of a switch of aromatase inhibitors on musculoskeletal symptoms in postmenopausal women with hormone-receptor-positive breast cancer: the ATOLL (articular tolerance of letrozole) study. Breast Cancer Res Treat 120:127–134

    Article  PubMed  CAS  Google Scholar 

  46. Henry NL, Giles JT, Stearns V (2008) Aromatase inhibitor-associated musculoskeletal symptoms: etiology and strategies for management. Oncology (Williston Park) 22:1401–1408

    Google Scholar 

  47. Din OS, Dodwell D, Wakefield RJ, Coleman RE (2010) Aromatase inhibitor-induced arthralgia in early breast cancer: what do we know and how can we find out more? Breast Cancer Res Treat 120:525–538

    Article  PubMed  CAS  Google Scholar 

  48. Dizdar O, Ozcakar L, Malas FU et al (2009) Sonographic and electrodiagnostic evaluations in patients with aromatase inhibitor-related arthralgia. J Clin Oncol 27:4955–4960

    Article  PubMed  Google Scholar 

  49. Henry NL, Charles P, Pshezhetskiy D et al (2008) A distinct inflammatory marker pattern in patients with aromatase inhibitor (AI)-induced musculoskeletal symptoms (abstr 1129). In: 31st Annual San Antonio Breast Cancer Symposium, San Antonio, TX

  50. Morales L, Pans S, Verschueren K et al (2008) Prospective study to assess short-term intra-articular and tenosynovial changes in the aromatase inhibitor-associated arthralgia syndrome. J Clin Oncol 26:3147–3152

    Article  PubMed  Google Scholar 

  51. Robidoux A, Rich E, Bureau NJ et al (2009) A prospective pilot study investigating the nature, the onset, and the incidence of joint pain in menopausal, breast cancer patients receiving aromatase inhibitor (AI) therapy (abstr 4090). In: 32nd Annual San Antonio Breast Cancer Symposium, San Antonio, TX

  52. Sestak I, Cuzick J, Sapunar F et al (2008) Risk factors for joint symptoms in patients enrolled in the ATAC trial: a retrospective, exploratory analysis. Lancet Oncol 9:866–872

    Article  PubMed  Google Scholar 

  53. Ingle JN, Schaid DJ, Goss PE et al (2010) Genome-wide associations and functional genomic studies of musculoskeletal adverse events in women receiving aromatase inhibitors. J Clin Oncol 28:4674–4682

    Article  PubMed  CAS  Google Scholar 

  54. Chlebowski RT (2009) Aromatase inhibitor-associated arthralgias. J Clin Oncol 27:4932–4934

    Article  PubMed  Google Scholar 

  55. Coleman RE, Bolten WW, Lansdown M et al (2008) Aromatase inhibitor-induced arthralgia: clinical experience and treatment recommendations. Cancer Treat Rev 34:275–282

    Article  PubMed  CAS  Google Scholar 

  56. Younus J, Kligman L (2010) Management of aromatase inhibitor-induced arthralgia. Curr Oncol 17:87–90

    PubMed  CAS  Google Scholar 

  57. Briest S, Stearns V (2008) Adjuvant aromatase inhibitors and emerging quality-of-life considerations. Expert Rev Anticancer Ther 8:1–4

    Article  PubMed  CAS  Google Scholar 

  58. Burstein HJ (2007) Aromatase inhibitor-associated arthralgia syndrome. Breast 16:223–234

    Article  PubMed  Google Scholar 

  59. Nelson LR, Bulun SE (2001) Estrogen production and action. J Am Acad Dermatol 45:S116–S124

    Article  PubMed  CAS  Google Scholar 

  60. Thorne C (2007) Clinical management of arthralgia and bone health in women undergoing aromatase inhibitor therapy. Curr Opin Oncol 19:S19–S28

    Article  CAS  Google Scholar 

  61. Winters L, Habin K, Gallagher J (2007) Aromatase inhibitors and musculoskeletal pain in patients with breast cancer. Clin J Oncol Nurs 11:433–439

    Article  PubMed  Google Scholar 

  62. Thorne C (2007) Management of arthralgias associated with aromatase inhibitor therapy. Curr Oncol 14(1):S11–S19

    Article  PubMed  Google Scholar 

  63. Holick MF (2003) Vitamin D deficiency: what a pain it is. Mayo Clin Proc 78:1457–1459

    Article  PubMed  Google Scholar 

  64. Ott CD, Waltman NL, Twiss JJ (2007) Vitamin D insufficiency and musculoskeletal symptoms in breast cancer survivors on aromatase inhibitor therapy. Bone 40:S310

    Google Scholar 

  65. Waltman NL, Ott CD, Twiss JJ, Gross GJ, Lindsey AM (2009) Vitamin D insufficiency and musculoskeletal symptoms in breast cancer survivors on aromatase inhibitor therapy. Cancer Nurs 32:143–150

    Article  PubMed  Google Scholar 

  66. Rastelli A, Taylor M, Villareal R et al (2009) A double-blind, randomized, placebo-controlled trial of high dose Vitamin D therapy on musculoskeletal pain and bone mineral density in anastrozole-treated breast cancer patients with marginal Vitamin D status (abstr 803). In: 32nd Annual San Antonio Breast Cancer Symposium, San Antonio, TX

  67. Souberbielle JC, Body JJ, Lappe JM et al (2010) Vitamin D and musculoskeletal health, cardiovascular disease, autoimmunity and cancer: recommendations for clinical practice. Autoimmun Rev 9:709–715

    Article  PubMed  CAS  Google Scholar 

  68. Bischoff-Ferrari H (2009) Vitamin D: what is an adequate vitamin D level and how much supplementation is necessary? Best Pract Res Clin Rheumatol 23:789–795

    Article  PubMed  CAS  Google Scholar 

  69. Leitzmann MF, Moore SC, Peters TM et al (2008) Prospective study of physical activity and risk of postmenopausal breast cancer. Breast Cancer Res 10:R92

    Article  PubMed  Google Scholar 

  70. Chlebowski RT, Geller ML (2006) Adherence to endocrine therapy for breast cancer. Oncology 71:1–9

    PubMed  CAS  Google Scholar 

  71. Shapiro CL (2005) Aromatase inhibitors and bone loss: risks in perspective. J Clin Oncol 23:4847–4849

    Article  PubMed  CAS  Google Scholar 

  72. Body JJ, Bergmann P, Boonen S et al (2007) Management of cancer treatment-induced bone loss in early breast and prostate cancer—a consensus paper of the Belgian Bone Club. Osteoporos Int 18:1439–1450

    Article  PubMed  CAS  Google Scholar 

  73. Goss PE, Hadji P, Subar M et al (2007) Effects of steroidal and nonsteroidal aromatase inhibitors on markers of bone turnover in healthy postmenopausal women. Breast Cancer Res 9:R52

    Article  PubMed  Google Scholar 

  74. McCloskey EV, Hannon RA, Lakner G et al (2007) Effects of third generation aromatase inhibitors on bone health and other safety parameters: results of an open, randomised, multi-centre study of letrozole, exemestane and anastrozole in healthy postmenopausal women. Eur J Cancer 43:2523–2531

    Article  PubMed  CAS  Google Scholar 

  75. Geisler J, Lonning PE, Krag LE et al (2006) 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 42:2968–2975

    Article  PubMed  CAS  Google Scholar 

  76. Perez EA (2007) Safety profiles of tamoxifen and the aromatase inhibitors in adjuvant therapy of hormone-responsive early breast cancer. Ann Oncol 18 Suppl 8:viii26–35

    Google Scholar 

  77. van de Velde CJH (2009) Results of TEAM (Tamoxifen and Exemestane adjuvant multinational trial): a prospective, randomized, phase III trial in hormone-sensitive postmenopausal early breast cancer (oral presentation). In: Joint ECCO 15–34th ESMO Multidisciplinary Congress, Berlin, Germany

  78. Jakesz R, Jonat W, Gnant M et al (2005) 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 366:455–462

    Article  PubMed  CAS  Google Scholar 

  79. National Osteoporosis Foundation Clinician’s Guide to Prevention and Treatment of Osteoporosis. http://www.nof.org/professionals/NOF_Clinicians_Guide.pdf. Accessed 11 Mar 2009

  80. Hillner BE, Ingle JN, Chlebowski RT et al (2003) American Society of Clinical Oncology 2003 update on the role of bisphosphonates and bone health issues in women with breast cancer. J Clin Oncol 21:4042–4057

    Article  PubMed  CAS  Google Scholar 

  81. Hadji P, Body JJ, Aapro MS et al (2008) Practical guidance for the management of aromatase inhibitor-associated bone loss. Ann Oncol 19:1407–1416

    Article  PubMed  CAS  Google Scholar 

  82. Monnier A (2008) Comparison of lipid and cardiovascular safety data of aromatase inhibitors (AIs) (poster). In: 6th European Breast Cancer Conference, Berlin, Germany

  83. Pritchard KI, Abramson BL (2006) Cardiovascular health and aromatase inhibitors. Drugs 66:1727–1740

    Article  PubMed  CAS  Google Scholar 

  84. Cuppone F, Bria E, Verma S et al (2008) Do adjuvant aromatase inhibitors increase the cardiovascular risk in postmenopausal women with early breast cancer? Meta-analysis of randomized trials. Cancer 112:260–267

    Article  PubMed  CAS  Google Scholar 

  85. Ligibel JA, O’Malley A, Fisher M et al (2010) Aromatase inhibitors and risk of myocardial infarction, stroke, and fracture (abstr S2-6). In: 33rd Annual San Antonio Breast Cancer Symposium, San Antonio, TX

  86. US Food and Drug Administration (2008) Arimidex (anastrozole) Tablets December 2008. http://www.fda.gov/Safety/MedWatch/SafetyInformation/Safety-RelatedDrugLabelingChanges/ucm125179.htm. Accessed 13 Jan 2011

  87. Amir E, Ocana A, Niraula S, Carlsson L, Seruga B (2010) Toxicity of adjuvant endocrine therapy in postmenopausal breast cancer patients (Abstract S2-7). Paper presented at the 33rd annual San Antonio breast cancer symposium, San Antonio, TX

  88. Collins B, Mackenzie J, Stewart A, Bielajew C, Verma S (2009) Cognitive effects of chemotherapy in post-menopausal breast cancer patients 1 year after treatment. Psychooncology 18:134–143

    Article  PubMed  Google Scholar 

  89. Zivian MT, Salgado B (2008) Side effects revisited: women’s experiences with aromatase inhibitors. A report from Breast Cancer Action. http://bcation.org/uploads/PDF/AIReport.pdf. Accessed 22 Dec 2009

  90. Sherwin BB (2003) Estrogen and cognitive functioning in women. Endocr Rev 24:133–151

    Article  PubMed  CAS  Google Scholar 

  91. Hogervorst E, Bandelow S (2010) Sex steroids to maintain cognitive function in women after the menopause: a meta-analyses of treatment trials. Maturitas 66:56–71

    Article  PubMed  CAS  Google Scholar 

  92. Resnick SM, Espeland MA, An Y et al (2009) Effects of conjugated equine estrogens on cognition and affect in postmenopausal women with prior hysterectomy. J Clin Endocrinol Metab 94:4152–4161

    Article  PubMed  CAS  Google Scholar 

  93. Lejbak L, Vrbancic M, Crossley M (2010) Endocrine therapy is associated with low performance on some estrogen-sensitive cognitive tasks in postmenopausal women with breast cancer. J Clin Exp Neuropsychol 32:836–846

    Article  PubMed  Google Scholar 

  94. Jenkins V, Shilling V, Fallowfield L, Howell A, Hutton S (2004) Does hormone therapy for the treatment of breast cancer have a detrimental effect on memory and cognition? A pilot study. Psychooncology 13:61–66

    Article  PubMed  Google Scholar 

  95. Collins B, Mackenzie J, Stewart A, Bielajew C, Verma S (2009) Cognitive effects of hormonal therapy in early stage breast cancer patients: a prospective study. Psychooncology 18:811–821

    Article  PubMed  Google Scholar 

  96. Schilder CM, Eggens PC, Seynaeve C et al (2009) Neuropsychological functioning in postmenopausal breast cancer patients treated with tamoxifen or exemestane after AC-chemotherapy: cross-sectional findings from the neuropsychological TEAM-side study. Acta Oncol 48:76–85

    Article  PubMed  CAS  Google Scholar 

  97. Schilder CM, Seynaeve C, Beex LV et al (2010) Effects of tamoxifen and exemestane on cognitive functioning of postmenopausal patients with breast cancer: results from the neuropsychological side study of the tamoxifen and exemestane adjuvant multinational trial. J Clin Oncol 28:1294–1300

    Article  PubMed  CAS  Google Scholar 

  98. Derzko C, Elliott S, Lam W (2007) Management of sexual dysfunction in postmenopausal breast cancer patients taking adjuvant aromatase inhibitor therapy. Curr Oncol 14(1):S20–S40

    Article  PubMed  Google Scholar 

  99. Cella D, Fallowfield LJ (2008) Recognition and management of treatment-related side effects for breast cancer patients receiving adjuvant endocrine therapy. Breast Cancer Res Treat 107:167–180

    Article  PubMed  CAS  Google Scholar 

  100. Paquet L, Frechette DA, Dent SF, Song X, Verma S (2010) Sexual distress in early breast cancer (EBC) survivors (abstr e19595). J Clin Oncol 28:15s(e suppl)

  101. Asmar L, Cantrell J, Vukelja Sj et al (2005) Final analysis of a planned comparison of menopausal symptoms in 1618 patients receiving either exemestane (E) or tamoxifen (T) in a blinded adjuvant hormonal study (abstr 2039). Breast Cancer Res Treat 94:S97

    Google Scholar 

  102. American College of Obstetricians and Gynecologists Committee on Gynecologic Practice (2006) ACOG committee opinion. No. 336: Tamoxifen and uterine cancer. Obstet Gynecol 107:1475–1478

    Article  Google Scholar 

  103. Sehdev S, Martin G, Sideris L, Lam W, Brisson S (2009) Safety of adjuvant endocrine therapies in hormone receptor-positive early breast cancer. Curr Oncol 16:S14–S23

    Article  PubMed  Google Scholar 

  104. Kelly CM, Juurlink DN, Gomes T et al (2010) Selective serotonin reuptake inhibitors and breast cancer mortality in women receiving tamoxifen: a population based cohort study. BMJ 340:c693

    Article  PubMed  Google Scholar 

  105. Kendall A, Dowsett M, Folkerd E, Smith I (2006) Caution: vaginal estradiol appears to be contraindicated in postmenopausal women on adjuvant aromatase inhibitors. Ann Oncol 17:584–587

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

The authors thank Stacey Simmons, MD, Pfizer Inc., for her insights and review of the manuscript. Medical editorial support was provided by Tamalette Loh, PhD, at AccuVerus, Beachwood, OH, and was funded by Pfizer Inc. The authors are fully responsible for all content and editorial decisions and did not receive compensation for development of the manuscript.

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  1. The Ottawa Hospital Cancer Centre, The University of Ottawa, 501 Smyth Rd, Ottawa, ON, K1H 8L6, Canada

    Susan F. Dent

  2. Pfizer Canada Inc., Kirkland, QC, Canada

    Rania Gaspo

  3. Medical Information, Pfizer Inc., New York, NY, USA

    Michelle Kissner

  4. Sunnybrook Odette Cancer Centre, The University of Toronto, Toronto, ON, Canada

    Kathleen I. Pritchard

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  1. Susan F. Dent
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  2. Rania Gaspo
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Correspondence to Susan F. Dent.

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Dent, S.F., Gaspo, R., Kissner, M. et al. Aromatase inhibitor therapy: toxicities and management strategies in the treatment of postmenopausal women with hormone-sensitive early breast cancer. Breast Cancer Res Treat 126, 295–310 (2011). https://doi.org/10.1007/s10549-011-1351-3

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