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01-11-2012 | Epidemiology

Aromatase inhibitors in obese breast cancer patients are not associated with increased plasma estradiol levels

Authors: Caroline Diorio, Julie Lemieux, Louise Provencher, Jean-Charles Hogue, Éric Vachon

Published in: Breast Cancer Research and Treatment | Issue 2/2012

Abstract

Obesity, in postmenopausal women, has been associated to a higher breast cancer incidence and worst prognosis. Some studies suggested a decrease in aromatase inhibitors (AI) efficacy in obese postmenopausal breast cancer patients, although estradiol levels were not measured. The purpose of the present study was to verify if estradiol levels are measurable in postmenopausal women under AI. If achievable, the goal is to compare the estradiol levels in lean versus obese postmenopausal women under AI treatment for non-metastatic breast cancer. Postmenopausal women were recruited in accordance to one of these four groups: lean [body mass index (BMI) of 18–25 kg/m²] under AI (n = 30), obese (BMI ≥30 kg/m²) under AI (n = 30), lean AI-naïve (n = 10), and obese AI-naïve (n = 10). Lean and obese women were matched according to their age. Estradiol levels were measured in plasma using an ELISA. The Wilcoxon signed-rank test was used to assess the significance of the differences between the groups. Estradiol levels in postmenopausal women under AI varied from 0 to 94.65 pg/ml with a median value of 0.98 pg/ml. Obese AI-naïve women had higher estradiol levels than lean AI-naïve women (p = 0.03). There was no difference in estradiol levels between lean and obese women under AI (p = 0.76). Despite very low plasma levels, it is possible to measure the estradiol levels in postmenopausal women under AI treatment. Our results suggest that the known impact of obesity on recurrence risk in women under AI treatment may not be due to incomplete aromatase inhibition. Further works are needed to examine closely the aromatase-independent pathways that are linking obesity to breast cancer risk and recurrence.

Siegel R, Ward E, Brawley O, Jemal A (2011) Cancer statistics, 2011: the impact of eliminating socioeconomic and racial disparities on premature cancer deaths. CA Cancer J Clin 61(4):212–236. doi:10.3322/caac.20121 PubMedCrossRef

Anderson WF, Katki HA, Rosenberg PS (2011) Incidence of breast cancer in the United States: current and future trends. J Natl Cancer Inst 103(18):1397–1402. doi:10.1093/jnci/djr257 PubMedCrossRef

Carlson RW, Allred DC, Anderson BO, Burstein HJ, Carter WB, Edge SB, Erban JK, Farrar WB, Forero A, Giordano SH, Goldstein LJ, Gradishar WJ, Hayes DF, Hudis CA, Ljung BM, Mankoff DA, Marcom PK, Mayer IA, McCormick B, Pierce LJ, Reed EC, Sachdev J, Smith ML, Somlo G, Ward JH, Wolff AC, Zellars R (2011) NCCN clinical practice guidelines in oncology: breast cancer, V.2.2011 edn. National Comprehensive Cancer Network (NCCN), Fort Washington

Miller WR (2006) Aromatase and the breast: regulation and clinical aspects. Maturitas 54(4):335–341. doi:10.1016/j.maturitas.2006.04.020 PubMedCrossRef

International Association for the Study of Obesity (2012) http://www.iaso.org/. Accessed 28 June 2012

Renehan AG, Tyson M, Egger M, Heller RF, Zwahlen M (2008) Body-mass index and incidence of cancer: a systematic review and meta-analysis of prospective observational studies. Lancet 371(9612):569–578. doi:10.1016/S0140-6736(08)60269-X PubMedCrossRef

Montazeri A, Sadighi J, Farzadi F, Maftoon F, Vahdaninia M, Ansari M, Sajadian A, Ebrahimi M, Haghighat S, Harirchi I (2008) Weight, height, body mass index and risk of breast cancer in postmenopausal women: a case-control study. BMC Cancer 8:278. doi:10.1186/1471-2407-8-278 PubMedCrossRef

Brown KA, Simpson ER (2010) Obesity and breast cancer: progress to understanding the relationship. Cancer Res 70(1):4–7. doi:10.1158/0008-5472.CAN-09-2257 PubMedCrossRef

Enger SM, Greif JM, Polikoff J, Press M (2004) Body weight correlates with mortality in early-stage breast cancer. Arch Surg 139(9):954–958. doi:10.1001/archsurg.139.9.954 (discussion 958–960)

10.

Maccio A, Madeddu C, Mantovani G (2009) Adipose tissue as target organ in the treatment of hormone-dependent breast cancer: new therapeutic perspectives. Obes Rev 10(6):660–670. doi:10.1111/j.1467-789X.2009.00592.x PubMedCrossRef

11.

Geisler J, Haynes B, Ekse D, Dowsett M, Lonning PE (2007) Total body aromatization in postmenopausal breast cancer patients is strongly correlated to plasma leptin levels. J Steroid Biochem Mol Biol 104(1–2):27–34. doi:10.1016/j.jsbmb.2006.09.040 PubMedCrossRef

12.

Miller WR, Anderson TJ, Evans DB, Krause A, Hampton G, Dixon JM (2003) An integrated view of aromatase and its inhibition. J Steroid Biochem Mol Biol 86(3–5):413–421PubMedCrossRef

13.

Sestak I, Distler W, Forbes JF, Dowsett M, Howell A, Cuzick J (2010) Effect of body mass index on recurrences in tamoxifen and anastrozole treated women: an exploratory analysis from the ATAC trial. J Clin Oncol 28(21):3411–3415. doi:10.1200/JCO.2009.27.2021 PubMedCrossRef

14.

Ware JE, Jr. SF-36^® Health Survey Update. http://www.sf-36.org/tools/sf36.shtml. Accessed 27 Aug 2012

15.

Ware JE Jr, Sherbourne CD (1992) The MOS 36-item short-form health survey (SF-36). I. Conceptual framework and item selection. Med Care 30(6):473–483PubMedCrossRef

16.

Hilditch JR, Lewis J, Peter A, van Maris B, Ross A, Franssen E, Guyatt GH, Norton PG, Dunn E (1996) A menopause-specific quality of life questionnaire: development and psychometric properties. Maturitas 24(3):161–175PubMedCrossRef

17.

Radtke JV, Terhorst L, Cohen SM (2011) The menopause-specific quality of Life Questionnaire: psychometric evaluation among breast cancer survivors. Menopause 18(3):289–295. doi:10.1097/gme.0b013e3181ef975a PubMedCrossRef

18.

Park MH, Falconer C, Viner RM, Kinra S (2012) The impact of childhood obesity on morbidity and mortality in adulthood: a systematic review. Obes Rev. doi:10.1111/j.1467-789X.2012.01015.x

19.

Morimoto LM, White E, Chen Z, Chlebowski RT, Hays J, Kuller L, Lopez AM, Manson J, Margolis KL, Muti PC, Stefanick ML, McTiernan A (2002) Obesity, body size, and risk of postmenopausal breast cancer: the women’s health initiative (United States). Cancer Causes Control 13(8):741–751PubMedCrossRef

20.

Reeves GK, Pirie K, Beral V, Green J, Spencer E, Bull D (2007) Cancer incidence and mortality in relation to body mass index in the million women study: cohort study. BMJ 335(7630):1134. doi:10.1136/bmj.39367.495995.AE PubMedCrossRef

21.

Loi S, Milne RL, Friedlander ML, McCredie MR, Giles GG, Hopper JL, Phillips KA (2005) Obesity and outcomes in premenopausal and postmenopausal breast cancer. Cancer Epidemiol Biomarkers Prev 14(7):1686–1691. doi:10.1158/1055-9965.EPI-05-0042 PubMedCrossRef

22.

Protani M, Coory M, Martin JH (2010) Effect of obesity on survival of women with breast cancer: systematic review and meta-analysis. Breast Cancer Res Treat 123(3):627–635. doi:10.1007/s10549-010-0990-0 PubMedCrossRef

23.

Dignam JJ, Wieand K, Johnson KA, Fisher B, Xu L, Mamounas EP (2003) Obesity, tamoxifen use, and outcomes in women with estrogen receptor-positive early-stage breast cancer. J Natl Cancer Inst 95(19):1467–1476PubMedCrossRef

24.

Calle EE, Rodriguez C, Walker-Thurmond K, Thun MJ (2003) Overweight, obesity, and mortality from cancer in a prospectively studied cohort of U.S. adults. N Engl J Med 348(17):1625–1638. doi:10.1056/NEJMoa021423 PubMedCrossRef

25.

Whiteman MK, Hillis SD, Curtis KM, McDonald JA, Wingo PA, Marchbanks PA (2005) Body mass and mortality after breast cancer diagnosis. Cancer Epidemiol Biomarkers Prev 14(8):2009–2014. doi:10.1158/1055-9965.EPI-05-0106 PubMedCrossRef

26.

Majed B, Moreau T, Senouci K, Salmon RJ, Fourquet A, Asselain B (2008) Is obesity an independent prognosis factor in woman breast cancer? Breast Cancer Res Treat 111(2):329–342. doi:10.1007/s10549-007-9785-3 PubMedCrossRef

27.

Petrelli JM, Calle EE, Rodriguez C, Thun MJ (2002) Body mass index, height, and postmenopausal breast cancer mortality in a prospective cohort of US women. Cancer Causes Control 13(4):325–332PubMedCrossRef

28.

Ewertz M, Jensen MB, Gunnarsdottir KA, Hojris I, Jakobsen EH, Nielsen D, Stenbygaard LE, Tange UB, Cold S (2011) Effect of obesity on prognosis after early-stage breast cancer. J Clin Oncol 29(1):25–31. doi:10.1200/JCO.2010.29.7614 PubMedCrossRef

29.

Lorincz AM, Sukumar S (2006) Molecular links between obesity and breast cancer. Endocr Relat Cancer 13(2):279–292. doi:10.1677/erc.1.00729 PubMedCrossRef

30.

Hursting SD, Berger NA (2010) Energy balance, host-related factors, and cancer progression. J Clin Oncol 28(26):4058–4065. doi:10.1200/JCO.2010.27.9935 PubMedCrossRef

31.

Formica V, Tesauro M, Cardillo C, Roselli M (2012) Insulinemia and the risk of breast cancer and its relapse. Diabetes Obes Metab. doi:10.1111/j.1463-1326.2012.01614.x

32.

Milazzo G, Giorgino F, Damante G, Sung C, Stampfer MR, Vigneri R, Goldfine ID, Belfiore A (1992) Insulin receptor expression and function in human breast cancer cell lines. Cancer Res 52(14):3924–3930PubMed

33.

Subbaramaiah K, Morris PG, Zhou XK, Morrow M, Du B, Giri D, Kopelovich L, Hudis CA, Dannenberg AJ (2012) Increased levels of COX-2 and prostaglandin E2 contribute to elevated aromatase expression in inflamed breast tissue of obese women. Cancer Discov 2(4):356–365. doi:10.1158/2159-8290.CD-11-0241 PubMedCrossRef

34.

Terry MB, Gammon MD, Zhang FF, Tawfik H, Teitelbaum SL, Britton JA, Subbaramaiah K, Dannenberg AJ, Neugut AI (2004) Association of frequency and duration of aspirin use and hormone receptor status with breast cancer risk. JAMA 291(20):2433–2440. doi:10.1001/jama.291.20.2433 PubMedCrossRef

35.

Rose DP, Gilhooly EM, Nixon DW (2002) Adverse effects of obesity on breast cancer prognosis, and the biological actions of leptin (review). Int J Oncol 21(6):1285–1292PubMed

36.

Revillion F, Charlier M, Lhotellier V, Hornez L, Giard S, Baranzelli MC, Djiane J, Peyrat JP (2006) Messenger RNA expression of leptin and leptin receptors and their prognostic value in 322 human primary breast cancers. Clin Cancer Res 12(7 Pt 1):2088–2094. doi:10.1158/1078-0432.CCR-05-1904 PubMedCrossRef

37.

Bulun SE, Chen D, Moy I, Brooks DC, Zhao H (2011) Aromatase, breast cancer and obesity: a complex interaction. Trends Endocrinol Metab 23(2):83–89. doi:10.1016/j.tem.2011.10.003 PubMed

38.

Schmid P, Possinger K, Bohm R, Chaudri H, Verbeek A, Grosse Y, Luftner D, Petrides PE, Sezer O, Wischnewsky M (2000) Body mass index as predictive parameter for response and time to progression (TTP) in advanced breast cancer patients treated with letrozole or megestrol acetate. Proc Am Soc Clin Oncol 19:103a (abstr 398)

39.

Pfeiler G, Konigsberg R, Fesl C, Mlineritsch B, Stoeger H, Singer CF, Postlberger S, Steger GG, Seifert M, Dubsky P, Taucher S, Samonigg H, Bjelic-Radisic V, Greil R, Marth C, Gnant M (2011) Impact of body mass index on the efficacy of endocrine therapy in premenopausal patients with breast cancer: an analysis of the prospective ABCSG-12 trial. J Clin Oncol 29(19):2653–2659. doi:10.1200/JCO.2010.33.2585 PubMedCrossRef

40.

Michaud L, Buzdar A, Rubin S, Steinberg M, Yin H, Aaronson L, Nabholtz J (2002) The efficacy of anastrozole is not dependent upon body mass index (BMI) in postmenopausal women with advanced breast cancer (BC). Proc Am Soc Clin Oncol 21:55a (abstr 219)

41.

Pfeiler G, Stöger H, Singer C, Seifert M, Jakesz R, Dubsky P, Samonigg H, Greil R, Menzel C, Heck D, Gnant M (2010) Impact of body mass index (BMI) on the efficacy of endocrine therapy in postmenopausal breast cancer patients—an analysis of the ABCSG 6 and 6a Trial. San Antonio Breast Cancer Conf abstract PD-09-05

42.

Folkerd EJ, Dixon JM, Renshaw L, A’Hern RP, Dowsett M (2012) Suppression of plasma estrogen levels by letrozole and anastrozole is related to body mass index in patients with breast cancer. J Clin Oncol 30(24):2977–2980. doi:10.1200/JCO.2012.42.0273 PubMedCrossRef

43.

Lonning PE, Geisler J (2008) Aromatase inhibitors: assessment of biochemical efficacy measured by total body aromatase inhibition and tissue estrogen suppression. J Steroid Biochem Mol Biol 108(3–5):196–202. doi:10.1016/j.jsbmb.2007.09.017 PubMedCrossRef

44.

Geisler J, Detre S, Berntsen H, Ottestad L, Lindtjorn B, Dowsett M, Einstein Lonning P (2001) Influence of neoadjuvant anastrozole (Arimidex) on intratumoral estrogen levels and proliferation markers in patients with locally advanced breast cancer. Clin Cancer Res 7(5):1230–1236PubMed

45.

Santen RJ, Song RX, Zhang Z, Kumar R, Jeng MH, Masamura A, Lawrence J Jr, Berstein L, Yue W (2005) Long-term estradiol deprivation in breast cancer cells up-regulates growth factor signaling and enhances estrogen sensitivity. Endocr Relat Cancer 12(Suppl 1):S61–S73. doi:10.1677/erc.1.01018 PubMedCrossRef

Title: Aromatase inhibitors in obese breast cancer patients are not associated with increased plasma estradiol levels
Authors: Caroline Diorio
Julie Lemieux
Louise Provencher
Jean-Charles Hogue
Éric Vachon
Publication date: 01-11-2012
Publisher: Springer US
Published in: Breast Cancer Research and Treatment / Issue 2/2012
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI: https://doi.org/10.1007/s10549-012-2278-z

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