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The impact of an aromatase inhibitor on body composition and gonadal hormone levels in women with breast cancer

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Abstract

Aromatase inhibitors (AIs) have become the standard adjuvant therapy of postmenopausal breast cancer survivors. AIs induce a reduction of bioavailable estrogens by inhibiting aromatase, which would be expected to induce alterations in body composition, more extensive than induced by menopause. The objectives are to examine the impact of AIs on (1) DXA-scan derived body composition and (2) gonadal hormone levels. This is a sub-analysis of a 2-year double-blind, placebo-controlled, randomized trial of 82 women with nonmetastatic breast cancer, newly menopausal following chemotherapy, who were randomized to risedronate (35 mg once weekly) versus placebo, and stratified for their usage of AI versus no AI. Outcomes included DXA-scan derived body composition and gonadal hormone levels. As a group, total body mass increased in women over 24 months. Women on AIs gained a significant amount of lean body mass compared to baseline as well as to no-AI users (P < 0.05). Women not on an AI gained total body fat compared to baseline and AI users (P < 0.05). Free testosterone significantly increased and sex hormone binding globulin (SHBG) significantly decreased in women on AIs compared to no AIs at 24 months (P < 0.01) while total estradiol and testosterone levels remained stable. Independent of AI usage, chemotherapy-induced postmenopausal breast cancer patients demonstrated an increase of total body mass. AI users demonstrated maintenance of total body fat, an increase in lean body mass and free testosterone levels, and a decrease in SHBG levels compared to no-AI users. The mechanisms and implications of these changes need to be studied further.

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References

  1. Dunnwald LK, Rossing MA, Li CI (2007) Hormone receptor status, tumor characteristics, and prognosis: a prospective cohort of breast cancer patients. Breast Cancer Res 9(1):R6

    Article  PubMed  Google Scholar 

  2. Smith IE, Dowsett M (2003) Aromatase inhibitors in breast cancer. N Engl J Med 348(24):2431–2442

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  4. Carr MC (2003) The emergence of the metabolic syndrome with menopause. J Clin Endocrinol Metab 88(6):2404–2411

    Article  CAS  PubMed  Google Scholar 

  5. Greenspan SL, Brufsky A, Lembersky BC, Bhattacharya R, Vujevich KT, Perera S, Sereika SM, Vogel VG (2008) Risedronate prevents bone loss in breast cancer survivors: a 2-year, randomized, double-blind, placebo-controlled clinical trial. J Clin Oncol 26(16):2644–2652

    Article  CAS  PubMed  Google Scholar 

  6. Fuerst T, Genant HK (1996) Evaluation of body compositlon and total bone mass with the hologic QDR 4500. Osteo Int 6(Suppl 1):203

    Google Scholar 

  7. Lee CC, Kasa-Vubu JZ, Supiano MA (2003) Differential effects of raloxifene and estrogen on insulin sensitivity in postmenopausal women. J Am Geriatr Soc 51(5):683–688

    Article  PubMed  Google Scholar 

  8. Francucci CM, Daniele P, Iori N, Camilletti A, Massi F, Boscaro M (2005) Effects of raloxifene on body fat distribution and lipid profile in healthy post-menopausal women. J Endocrinol Invest 28(7):623–631

    CAS  PubMed  Google Scholar 

  9. Tommaselli GA, Di Carlo C, Di Spiezio Sardo A, Bifulco G, Cirillo D, Guida M, Capasso R, Nappi C (2006) Serum leptin levels and body composition in postmenopausal women treated with tibolone and raloxifene. Menopause 13(4):660–668

    Article  PubMed  Google Scholar 

  10. Jacobsen DE, Samson MM, Schouw YT, Grobbee DE, Verhaar HJ (2008) Efficacy of tibolone and raloxifene for the maintenance of skeletal muscle strength, bone mineral density, balance, body composition, cognitive function, mood/depression, anxiety and quality of life/well-being in late postmenopausal women >/=70 years: study design of a randomized, double-blind, double-dummy, placebo-controlled, single-center trial. Trials 9:32

    Article  PubMed  Google Scholar 

  11. Nguyen MC, Stewart RB, Banerji MA, Gordon DH, Kral JG (2001) Relationships between tamoxifen use, liver fat and body fat distribution in women with breast cancer. Int J Obes Relat Metab Disord 25(2):296–298

    Article  CAS  PubMed  Google Scholar 

  12. Grey A, Stapleton J, Evans M, Reid I (1995) The effect of the anti-estrogen tamoxifen on cardiovascular risk factors in normal postmenopausal women. J Clin Endocrinol Metab 80(11):3191–3195

    Article  CAS  PubMed  Google Scholar 

  13. Francini G, Petrioli R, Montagnani A, Cadirni A, Campagna S, Francini E, Gonnelli S (2006) Exemestane after tamoxifen as adjuvant hormonal therapy in postmenopausal women with breast cancer: effects on body composition and lipids. Br J Cancer 95(2):153–158

    Article  CAS  PubMed  Google Scholar 

  14. Enns DL, Tiidus PM (2010) The influence of estrogen on skeletal muscle: sex matters. Sports Med 40(1):41–58

    Article  PubMed  Google Scholar 

  15. Yates RA, Dowsett M, Fisher GV, Selen A, Wyld PJ (1996) Arimidex (ZD1033): a selective, potent inhibitor of aromatase in postmenopausal female volunteers. Br J Cancer 73(4):543–548

    CAS  PubMed  Google Scholar 

  16. Bajetta E, Zilembo N, Dowsett M, Guillevin L, Di Leo A, Celio L, Martinetti A, Marchiano A, Pozzi P, Stani S et al (1999) Double-blind, randomised, multicentre endocrine trial comparing two letrozole doses, in postmenopausal breast cancer patients. Eur J Cancer 35(2):208–213

    Article  CAS  PubMed  Google Scholar 

  17. Bhasin S, Woodhouse L, Storer TW (2001) Proof of the effect of testosterone on skeletal muscle. J Endocrinol 170(1):27–38

    Article  CAS  PubMed  Google Scholar 

  18. Miller KK (2009) Androgen deficiency: effects on body composition. Pituitary 12(2):116–124

    Article  CAS  PubMed  Google Scholar 

  19. Ling S, Komesaroff PA, Sudhir K (2009) Cardiovascular physiology of androgens and androgen testosterone therapy in postmenopausal women. Endocr Metab Immune Disord Drug Targets 9(1):29–37

    Article  CAS  PubMed  Google Scholar 

  20. Torrens JI, Sutton-Tyrrell K, Zhao X, Matthews K, Brockwell S, Sowers M, Santoro N (2009) Relative androgen excess during the menopausal transition predicts incident metabolic syndrome in midlife women: study of Women’s Health Across the Nation. Menopause 16(2):257–264

    Article  PubMed  Google Scholar 

  21. Janssen I, Powell LH, Crawford S, Lasley B, Sutton-Tyrrell K (2008) Menopause and the metabolic syndrome: the Study of Women’s Health Across the Nation. Arch Intern Med 168(14):1568–1575

    Article  CAS  PubMed  Google Scholar 

  22. Ding EL, Song Y, Manson JE, Hunter DJ, Lee CC, Rifai N, Buring JE, Gaziano JM, Liu S (2009) Sex hormone-binding globulin and risk of type 2 diabetes in women and men. N Engl J Med 361(12):1152–1163

    Article  CAS  PubMed  Google Scholar 

  23. Perry JR, Weedon MN, Langenberg C, Jackson AU, Lyssenko V, Sparso T, Thorleifsson G, Grallert H, Ferrucci L, Maggio M et al (2010) Genetic evidence that raised sex hormone binding globulin (SHBG) levels reduce the risk of type 2 diabetes. Hum Mol Genet 19(3):535–544

    Article  CAS  PubMed  Google Scholar 

  24. Abdulhaq H, Geyer C (2008) Safety of adjuvant endocrine therapy in postmenopausal women with breast cancer. Am J Clin Oncol 31(6):595–605

    Article  CAS  PubMed  Google Scholar 

  25. Ewer MS, Gluck S (2009) A woman’s heart: the impact of adjuvant endocrine therapy on cardiovascular health. Cancer 115(9):1813–1826

    Article  CAS  PubMed  Google Scholar 

  26. Gandhi S, Verma S (2007) Aromatase inhibitors and cardiac toxicity: getting to the heart of the matter. Breast Cancer Res Treat 106(1):1–9

    Article  CAS  PubMed  Google Scholar 

  27. Lewis S (2007) Do endocrine treatments for breast cancer have a negative impact on lipid profiles and cardiovascular risk in postmenopausal women? Am Heart J 153(2):182–188

    Article  CAS  PubMed  Google Scholar 

  28. Seruga B, Tannock IF (2009) Up-front use of aromatase inhibitors as adjuvant therapy for breast cancer: the emperor has no clothes. J Clin Oncol 27(6):840–842

    Article  PubMed  Google Scholar 

  29. Janssen I, Powell LH, Kazlauskaite R, Dugan SA (2009) Testosterone and visceral fat in midlife women: the Study of Women’s Health Across the Nation (SWAN) fat patterning study. Obesity 18(3):604–610

    Article  PubMed  Google Scholar 

  30. Jacobsen D, Samson M, Emmelot M, Verhaar H (2009) Raloxifene and body composition and muscle strength in postmenopausal women: a randomized, double-blind, placebo-controlled trial. Eur J Endocrinol 162:371–376

    Article  PubMed  Google Scholar 

  31. Santen RJ, Brodie H, Simpson ER, Siiteri PK, Brodie A (2010) History of aromatase: saga of an important biological mediator and therapeutic target. Endocr Rev 30(4):343–375

    Article  Google Scholar 

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Acknowledgments

All funding sources supporting publication of a work or study are as follows. NIH/NIDDKD (K24: DK062895-05): awarded to Dr. Greenspan. A Procter and Gamble and Sanofi-Aventis noncompany-sponsored trial grant: awarded to Dr. Greenspan. NIH/NCRR (M01-RR00056): awarded to the University of Pittsburgh. NIH/NCRR (RR024154): awarded to Dr. Steven E. Reis. John A. Hartford foundation (2004-0485): provided support for assays. None of these funding agencies were involved in the design and conduct of the study; collection, management, analysis, and interpretation of the data; or preparation, review, and approval of the manuscript. Risedronate, matching placebo, calcium, and vitamin D supplements were provided by Procter and Gamble, Inc. We are indebted to the nursing, professional, laboratory, dietary, administrative, and study staff of the Clinical Translational Research Center of Montefiore University Hospital and Osteoporosis Prevention and Treatment Center at the University of Pittsburgh. We acknowledge the members of the Data and Safety Monitoring Board for their oversight of the study.

Conflict of interest

Dr Greenspan has received grant-support from Procter and Gamble, Inc., Sanofi-Aventis, Amgen, and Lilly. Dr Greenspan also serves as a consultant for Merck. Dr. Perera has received funding in the past from Eli Lilly and Co., Ortho Biotech, LLC, Teva Neuroscience for observational research. All other authors have no conflict of interest.

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Authors and Affiliations

  1. Medicine, University of Pittsburgh, 3471 Fifth Ave, Suite 500 Kaufmann Medical Bldg, Pittsburgh, PA, 15213, USA

    G. J. van Londen, S. Perera, K. Vujevich, P. Rastogi, B. Lembersky, A. Brufsky & S. L. Greenspan

  2. Cancer Institute, Geisinger Medical Center, Danville, PA, USA

    V. Vogel

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  1. G. J. van Londen
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  2. S. Perera
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  3. K. Vujevich
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  4. P. Rastogi
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  5. B. Lembersky
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  6. A. Brufsky
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  7. V. Vogel
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  8. S. L. Greenspan
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Correspondence to G. J. van Londen.

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van Londen, G.J., Perera, S., Vujevich, K. et al. The impact of an aromatase inhibitor on body composition and gonadal hormone levels in women with breast cancer. Breast Cancer Res Treat 125, 441–446 (2011). https://doi.org/10.1007/s10549-010-1223-2

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  • DOI: https://doi.org/10.1007/s10549-010-1223-2

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