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Serum Soluble Epidermal Growth Factor Receptor Concentrations Decrease in Postmenopausal Metastatic Breast Cancer Patients Treated with Letrozole

¹ Tumor Biology Program, Cancer Center Statistics Unit, Departments of ² Health Sciences Research and ³ Medical Oncology, Mayo Clinic College of Medicine, Rochester, Minnesota; ⁴ Department of Internal Medicine, Division of Hematology/Oncology, Kentucky College of Public Health, Markey Cancer Center, University of Kentucky, Lexington, Kentucky; ⁵ Department of Biochemistry and Nutrition, School of Medicine, Medical Sciences Campus, University of Puerto Rico, San Juan, Puerto Rico; ⁶ Department of Hematology/Oncology, Mayo Clinic College of Medicine, Jacksonville, Florida; and ⁷ Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale University School of Medicine, New Haven, Connecticut

Requests for reprints: Nita J. Maihle, Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, 300 George Street, Suite 8100, New Haven, CT 06511. Phone: 203-785-5212; Fax: 203-737-2914; E-mail: nita.maihle{at}yale.edu.

Previous studies have implicated estrogen as a regulator of epidermal growth factor receptor (EGFR) expression in breast tumors. We therefore speculated that estrogen might modulate serologic soluble EGFR (sEGFR) concentrations in breast cancer patients. Accordingly, we measured serum sEGFR concentrations in postmenopausal women with metastatic breast cancer (MBC) treated with letrozole, an aromatase inhibitor that blocks estrogen synthesis. Serum specimens were obtained prior to and following 1 and 3 months of letrozole therapy. We report that sEGFR concentrations do not differ between MBC patients prior to letrozole treatment and age- and postmenopause-matched healthy women (P = 0.468). In contrast, however, sEGFR concentrations decreased significantly in 76% of MBC patients after both 1 month (P = 0.006) and 3 months (P = 0.003) of letrozole therapy versus pretreatment concentrations. Within the limitations of this study, we found no evidence for an association between pretreatment sEGFR concentrations or decreased treatment sEGFR concentrations and either progression-free or overall survival. Nonetheless, we conclude that future prospective studies are warranted to determine if baseline and/or longitudinal serum sEGFR concentrations may be useful for predicting disease progression and survival, and/or for monitoring responsiveness to aromatase inhibitors or other endocrine therapies in breast cancer patients.