Aromatase inhibitors in obese breast cancer patients are not associated with increased plasma estradiol levels
- 406 Downloads
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.
KeywordsBreast cancer Aromatase inhibitor Estradiol Obesity
C.D. is a Junior Investigator of the Canadian Research Society (2011-700657). J.L. is a Clinical Research Scholar from the Fonds de Recherche du Québec—Santé (FRQS). This study was supported by an unrestricted grant from Pfizer Canada.
Conflict of Interest
Authors have no conflict of interest to declare.
- 3.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 WashingtonGoogle Scholar
- 5.International Association for the Study of Obesity (2012) http://www.iaso.org/. Accessed 28 June 2012
- 7.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 PubMedCrossRefGoogle Scholar
- 14.Ware JE, Jr. SF-36® Health Survey Update. http://www.sf-36.org/tools/sf36.shtml. Accessed 27 Aug 2012
- 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):741–751PubMedCrossRefGoogle Scholar
- 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
- 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 PubMedCrossRefGoogle Scholar
- 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 PubMedCrossRefGoogle Scholar
- 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 PubMedCrossRefGoogle Scholar
- 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)Google Scholar
- 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 PubMedCrossRefGoogle Scholar
- 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)Google Scholar
- 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-09-05Google Scholar
- 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 PubMedCrossRefGoogle Scholar