Letrozole is Superior to Anastrozole in Suppressing Breast Cancer Tissue and Plasma Estrogen Levels

Purpose: To evaluate the influence of the third-generation aromatase inhibitor letrozole (Femara) on breast cancer tissue levels of estrone (E 1 ), estradiol (E 2 ), and estrone sulfate (E 1 S) in postmenopausal women undergoing primary treatment for locally advanced estrogen receptor/progesterone r...

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Veröffentlicht in:Clinical cancer research 2008-10, Vol.14 (19), p.6330-6335
Hauptverfasser: GEISLER, Jürgen, HELLE, Hilgegunn, EKSE, Dagfinn, DUONG, Nhat K, EVANS, Dean B, NORDBØ, Yngve, AAS, Turid, LØNNING, Per E
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Sprache:eng
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Zusammenfassung:Purpose: To evaluate the influence of the third-generation aromatase inhibitor letrozole (Femara) on breast cancer tissue levels of estrone (E 1 ), estradiol (E 2 ), and estrone sulfate (E 1 S) in postmenopausal women undergoing primary treatment for locally advanced estrogen receptor/progesterone receptor–positive breast cancers. Experimental Design: Breast cancer tissue samples were collected before and following 4 months of neoadjuvant therapy with letrozole (2.5 mg o.d.), and tissue estrogen levels measured using a highly sensitive RIA after high-pressure liquid chromatography purification. Results: Letrozole suppressed pretreatment tumor levels of E 2 , E 1 , and E 1 S by 97.6%, 90.7%, and 90.1%, respectively. These data reveal that letrozole suppresses tissue estrogen levels significantly below what has previously been recorded with anastrozole (89.0%, 83.4%, and 72.9% suppression, respectively) using the same methods. To confirm the differential effect of letrozole and anastrozole on each plasma estrogen fraction, we re-analyzed plasma samples obtained from a previous intrapatient cross-over study comparing letrozole and anastrozole using an improved RIA (detection limits of 0.67, 1.14, and 0.55 pmol/L for E 2 , E 1 , and E 1 S, respectively). Letrozole consistently suppressed each plasma estrogen fraction below the levels recorded for anastrozole: E 2 (average suppression by 95.2% versus 92.8%; P = 0.018), E 1 (98.8% suppression versus 96.3%; P = 0.003), and E 1 S (98.9% suppression versus 95.3%; P = 0.003). Conclusion: Our data reveals that letrozole (2.5 mg o.d.) is more effective compared with anastrozole (1.0 mg o.d.) with respect to tissue as well as plasma estrogen suppression in patients with postmenopausal breast cancer.
ISSN:1078-0432
1557-3265
DOI:10.1158/1078-0432.CCR-07-5221