Maturitas 81 (2015) 327
Contents lists available at ScienceDirect
Maturitas journal homepage: www.elsevier.com/locate/maturitas
Letter to the Editor Normal breast tissue estrogen levels Dear Editor, The recent paper by Depypere et al. (doi.org/10.1016/ j.maturitas.2015.01.014) evaluating normal breast tissue estradiol origin addresses an important topic. Some additional details may add to the interpretation of their findings. The authors state that data on breast normal tissue estradiol levels are lacking. However, we recently reported normal tissue levels of estradiol, estrone and estrone sulphate across breast quadrants in pre- as well as postmenopausal women [1]. Regarding estrogen measurements in the low concentration range, non-specific interactions constitute a significant problem [2]. In contrast to Depypere and colleagues, we purified tissue samples by HPLC prior to radioimmunoassay analysis [3]; we found postmenopausal tissue estrogen levels significantly lower compared to earlier reports and mean estradiol of about half the level reported by Depypere et al. Patients on treatment with aromatase inhibitors experience >98% enzyme inhibition [4], reflected in profound suppression of tissue as well as plasma estrogen levels [5]. This contrasts the moderate drop in plasma as well as tissue estrogen levels recorded in patient treated with aromatase inhibitors in Depypere’s report. I concur with their statement that normal breast estrogens mainly have a circulating origin as outlined and discussed in detail elsewhere [6]. But contrasting the arguments by Depypere and colleagues, evidence suggests local breast aromatization to be of little importance; rather, elevated levels of tumor estradiol as compared to normal tissue seems due to estrogen receptor binding and disturbed dehydrogenase activity [7].
http://dx.doi.org/10.1016/j.maturitas.2015.03.005 0378-5122/© 2015 Elsevier Ireland Ltd. All rights reserved.
References [1] Lønning PE, Helle H, Duong NK, Ekse D, Aas T, Geisler J. Tissue estradiol is selectively elevated in receptor positive breast cancers while tumour estrone is reduced independent of receptor status. J Steroid Biochem Mol Biol 2009;117(1–3):31–41. [2] Geisler J, Ekse D, Helle H, Duong N, Lønning P. An optimised, highly sensitive radioimmunoassay for the simultaneous measurement of estrone, estradiol and estrone sulfate in the ultra-low range in human plasma samples. J Steroid Biochem Mol Biol 2008;109:90–5. [3] Geisler J, Berntsen H, Lønning P. A novel HPLC-RIA method for the simultaneous detection of estrone, estradiol and estrone sulphate levels in breast cancer tissue. J Steroid Biochem Mol Biol 2000;72:259–64. [4] Lønning PE. Aromatase inhibitors in breast cancer. End-Rel Cancer 2004;11:179–89. [5] Geisler J, Helle H, Ekse D, Duong NK, Evans DB, Nordbo Y, et al. Letrozole is superior to anastrozole in suppressing breast cancer tissue and plasma estrogen levels. Clin Cancer Res 2008;14(19):6330–5. [6] Lønning PE, Haynes BP, Straume AH, Dunbier A, Helle H, Knappskog S, et al. Exploring breast cancer estrogen disposition: the basis for endocrine manipulation. Clin Cancer Res 2011;17(15):4948–58. [7] Haynes BP, Straume AH, Geisler J, A’Hern R, Helle H, Smith IE, et al. Intratumoral estrogen disposition in breast cancer. Clin Cancer Res 2010;16(6):1790–801.
a
Per Eystein Lønning a,b,∗ Department of Clinical Science, Faculty of Medicine and Odontology, University of Bergen, Norway b Department of Clinical Oncology, Haukeland University Hospital, Bergen, Norway
∗ Correspondence to: Department of Clinical Science, Faculty of Medicine and Odontology, University of Bergen, Norway. Tel.: +47 55972027; fax: +47 55972046. E-mail address: [email protected]
5 March 2015
Contents lists available at ScienceDirect
Maturitas journal homepage: www.elsevier.com/locate/maturitas
Letter to the Editor Normal breast tissue estrogen levels Dear Editor, The recent paper by Depypere et al. (doi.org/10.1016/ j.maturitas.2015.01.014) evaluating normal breast tissue estradiol origin addresses an important topic. Some additional details may add to the interpretation of their findings. The authors state that data on breast normal tissue estradiol levels are lacking. However, we recently reported normal tissue levels of estradiol, estrone and estrone sulphate across breast quadrants in pre- as well as postmenopausal women [1]. Regarding estrogen measurements in the low concentration range, non-specific interactions constitute a significant problem [2]. In contrast to Depypere and colleagues, we purified tissue samples by HPLC prior to radioimmunoassay analysis [3]; we found postmenopausal tissue estrogen levels significantly lower compared to earlier reports and mean estradiol of about half the level reported by Depypere et al. Patients on treatment with aromatase inhibitors experience >98% enzyme inhibition [4], reflected in profound suppression of tissue as well as plasma estrogen levels [5]. This contrasts the moderate drop in plasma as well as tissue estrogen levels recorded in patient treated with aromatase inhibitors in Depypere’s report. I concur with their statement that normal breast estrogens mainly have a circulating origin as outlined and discussed in detail elsewhere [6]. But contrasting the arguments by Depypere and colleagues, evidence suggests local breast aromatization to be of little importance; rather, elevated levels of tumor estradiol as compared to normal tissue seems due to estrogen receptor binding and disturbed dehydrogenase activity [7].
http://dx.doi.org/10.1016/j.maturitas.2015.03.005 0378-5122/© 2015 Elsevier Ireland Ltd. All rights reserved.
References [1] Lønning PE, Helle H, Duong NK, Ekse D, Aas T, Geisler J. Tissue estradiol is selectively elevated in receptor positive breast cancers while tumour estrone is reduced independent of receptor status. J Steroid Biochem Mol Biol 2009;117(1–3):31–41. [2] Geisler J, Ekse D, Helle H, Duong N, Lønning P. An optimised, highly sensitive radioimmunoassay for the simultaneous measurement of estrone, estradiol and estrone sulfate in the ultra-low range in human plasma samples. J Steroid Biochem Mol Biol 2008;109:90–5. [3] Geisler J, Berntsen H, Lønning P. A novel HPLC-RIA method for the simultaneous detection of estrone, estradiol and estrone sulphate levels in breast cancer tissue. J Steroid Biochem Mol Biol 2000;72:259–64. [4] Lønning PE. Aromatase inhibitors in breast cancer. End-Rel Cancer 2004;11:179–89. [5] Geisler J, Helle H, Ekse D, Duong NK, Evans DB, Nordbo Y, et al. Letrozole is superior to anastrozole in suppressing breast cancer tissue and plasma estrogen levels. Clin Cancer Res 2008;14(19):6330–5. [6] Lønning PE, Haynes BP, Straume AH, Dunbier A, Helle H, Knappskog S, et al. Exploring breast cancer estrogen disposition: the basis for endocrine manipulation. Clin Cancer Res 2011;17(15):4948–58. [7] Haynes BP, Straume AH, Geisler J, A’Hern R, Helle H, Smith IE, et al. Intratumoral estrogen disposition in breast cancer. Clin Cancer Res 2010;16(6):1790–801.
a
Per Eystein Lønning a,b,∗ Department of Clinical Science, Faculty of Medicine and Odontology, University of Bergen, Norway b Department of Clinical Oncology, Haukeland University Hospital, Bergen, Norway
∗ Correspondence to: Department of Clinical Science, Faculty of Medicine and Odontology, University of Bergen, Norway. Tel.: +47 55972027; fax: +47 55972046. E-mail address: [email protected]
5 March 2015
