Letrozole was significantly superior to tamoxifen in TTP, TTF, ORR, and clinical benefit rate. Our results support its use as first-line endocrine therapy in postmenopausal women with advanced breast cancer.

This study shows that letrozole is more effective than tamoxifen as preoperative therapy in postmenopausal patients with ER and/or PgR positive primary untreated breast cancer and is at least as well tolerated.

This study documents the superiority of letrozole over tamoxifen in first-line endocrine therapy in postmenopausal women with advanced breast cancer.

Patients with normal serum HER-2/neu receiving letrozole demonstrated a significantly greater ORR and CB and longer TTP and TTF than patients receiving tamoxifen. Although in patients with elevated serum HER-2/neu there was no significant difference between letrozole and tamoxifen in ORR or CB, there was a strong trend favoring longer TTP and significantly longer TTF with letrozole.

BACKGROUND.Epidermal growth factor receptor (EGFR, HER‐1, and erbB1) is overexpressed in primary breast cancer and had been identified as a poor prognostic factor.METHODS.Pretreatment serum EGFR levels were quantified by using an enzyme‐linked immunoadsorbent assay in a Phase III first‐line trial of letrozole and tamoxifen and were correlated with patient outcomes.RESULTS.Serum EGFR levels in a control group of 117 healthy, postmenopausal women measured 64.1 ± 13.3 ng/mL (mean ± standard deviation). Using a cutoff EGFR level of 44.1 ng/mL from the control group (5% nonparametric method), 53 of 535 patients (10%) had decreased serum levels of EGFR. Patients with decreased serum EGFR had no significant difference in objective response rate (ORR), clinical benefit rate (CBR), time to progression (TTP), or time to treatment failure (TTF); however, they did have significantly reduced survival compared with patients who had normal serum EGFR levels (median survival, 23.3 months vs. 30.9 months; P = .007). A combined analysis of pretreatment serum EGFR and HER‐2 yielded no additional predictive information for ORR, CBR, TTP, or TTF compared to serum HER‐2 alone. However, in the current analysis, a subgroup of patients who had decreased serum EGFR and normal serum HER‐2 was identified (n = 39 of 535 patients; 7.3%) that had significantly reduced survival compared with patients who had normal serum levels of both EGFR and HER‐2 (median survival, 23.5 months vs. 37.1 months; P = .005). In multivariate analysis, a decreased serum EGFR level remained a significant independent prognostic factor for decreased survival (hazards ratio, 1.58; P = .007).CONCLUSIONS.In patients who had metastatic breast cancer, decreased serum EGFR/normal serum HER‐2 predicted shorter survival compared with patients who had normal levels of serum EGFR/HER‐2. This patient subgroup deserves further study to assess their response to and selection for anti‐EGFR‐directed therapies. Cancer 2006. © 2006 American Cancer Society.

Patients with elevated pretreatment serum TIMP-1 had a significantly reduced response and survival. Serum TIMP-1 was an independent predictive and prognostic factor. Blockade of TIMP-1 and HER-2/neu activity may be beneficial in a subset of patients with breast cancer.

Purpose. The letrozole study 025 is a large (n = 907), international, double-blind, randomized, phase III trial in postmenopausal women with advanced breast cancer. This subanalysis compares the efficacies of letrozole and tamoxifen as first-line therapy in postmenopausual women with advanced breast cancer according to site of metastatic lesions and Karnofsky Performance Status (KPS).Materials and Methods. Nine hundred seven patients with advanced breast cancer were randomly assigned to once-daily oral letrozole (2.5 mg; Femara ® ; Novartis Pharma AG; Basel, Switzerland) or tamoxifen (20 mg; Tamofen ® ; Leiras OY; Turku, Finland). Time to progression (TTP) was estimated using the KaplanMeier product-limit method. Treatments were compared by Cox proportional hazards regression models.Results. Letrozole treatment significantly prolonged TTP in all subsets of patients: those with nonvisceral metastases, those with visceral metastases without liver involvement, and those with liver metastases. The reduction in risk of progression ranged from 25%, for patients with nonvisceral metastases, to 36%, for patients with liver metastases. The distributions of baseline KPS scores for both treatment groupsThe Oncologist 2004;9:489-496 www.TheOncologist.com Correspondence: Hilary A. Chaudri-Ross, M.A., DEP, Novartis Pharma AG, WKL-490.1.04, CH-4057 Basel, Switzerland. Telephone: 41-61-696-1758; Fax: 41-61-696-1820; e-mail: hilary_anne.chaudri@pharma.novartis.com Received November 26, 2002; accepted for publication March 23, 2004. ©AlphaMed Press 1083-7159/2004 The Oncologist ® Breast Cancer LEARNING OBJECTIVESAfter completing this course, the reader will be able to:1. Identify which advanced breast cancer patients in the three subsets studied (with nonvisceral metastases, with visceral metastases without liver involvement, and with liver metastases) responded most favorably to first-line therapy.2. Describe the limitations of first-line treatment in the three subsets of patients with advanced breast cancer.3. Explain how KPS assessment correlates with overall survival in patients with advanced breast cancer with different sites of metastatic lesions.Access and take the CME test online and receive 1 hour of AMA PRA category 1 credit at CME.TheOncologist.com CME CME by guest on April 27, 2019http://theoncologist.alphamedpress.org/ Downloaded fromThis material is protected by U.S. Copyright law. Unauthorized reproduction is prohibited. For reprints contact: Reprints@AlphaMedPress.com Mouridsen, Sun, Gershanovich et al. 490 were similar (57% had KPS scores ≥90). Time to worsening of 20 points or more in KPS score was significantly longer with letrozole than with tamoxifen, but modest numbers of patients experienced such deterioration (letrozole, 20%, tamoxifen, 22%, in patients without visceral metastases; 23%-24% in patients with liver metastases; and letrozole, 14%, tamoxifen, 30%, in patients with visceral metastases without liver involvement).Conclusion. These data demonstrate the consistent superiority of letro...

Materials and Methods. Nine hundred seven patients with advanced breast cancer were randomly assigned to receive 2.5 mg letrozole (n = 453) or 20 mg tamoxifen (n = 454) once daily in a double-blind, multicenter, international trial. Among the prospectively planned analyses were analyses of TTP and ORR by age (<70 and ≥70 years). The results of these prospectively planned analyses are reported here.Results. Letrozole was as effective in older postmenopausal women (≥70 years of age) as it was in younger postmenopausal women (<70 years of age). The overall ORR in the older subgroup was significantly higher in patients treated with letrozole (38%) than in patients treated with tamoxifen (18%). In the younger subgroup of postmenopausal patients, the ORRs were not significantly different (letrozole, 26%; tamoxifen, 22%). TTP was significantly longer for letrozole than for tamoxifen in both age groups (younger: letrozole median TTP, 8.8 months; tamoxifen, 6.0 months; older: letrozole median TTP, 12.2 months; tamoxifen, 5.8 months). Although age was independently prognostic of TTP, there was no significant effect of age on ORR in the presence of other factors.Conclusion. The data show that letrozole, 2.5 mg once daily, is as effective in older, postmenopausal women as it is in younger postmenopausal women with advanced breast cancer. In addition, letrozole was more effective than tamoxifen in both younger and older patients. The Oncologist 2004;9:497-506