This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Geisler, J. Articles by Lønning, P. E. PubMed PubMed Citation Articles by Geisler, J. Articles by Lønning, P. E.

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

Authors' Affiliations: ¹ Faculty Division at the Akershus University Hospital, University of Oslo, Oslo, Norway, and Akershus University Hospital, Lørenskog, Norway; ² Institute of Medicine, University of Bergen, Norway, and Haukeland University Hospital, Department of Oncology, Bergen, Norway; ³ Oncology Research, Novartis Institutes for Biomedical Research, Novartis Pharma Ag, Basel, Switzerland; and ⁴ Haukeland University Hospital, Department of Surgery

Requests for reprints: Jürgen Geisler, Department of Oncology, Akershus University Hospital, 1478 Lørenskog, Norway. Phone: 47-6798-4658; Fax: 47-6798-4293; E-mail: jurgen.geisler{at}medisin.uio.no.

Purpose: To evaluate the influence of the third-generation aromatase inhibitor letrozole (Femara) on breast cancer tissue levels of estrone (E₁), estradiol (E₂), and estrone sulfate (E₁S) 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 E₂, E₁, and E₁S 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 E₂, E₁, and E₁S, respectively). Letrozole consistently suppressed each plasma estrogen fraction below the levels recorded for anastrozole: E₂ (average suppression by 95.2% versus 92.8%; P = 0.018), E₁ (98.8% suppression versus 96.3%; P = 0.003), and E₁S (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.