HER-2 Amplification, HER-1 Expression, and Tamoxifen Response in Estrogen Receptor-Positive Metastatic Breast Cancer

• DOI: 10.1158/1078-0432.ccr-04-0110
• Publication Date: 2005-09-21T23:58:40Z
• Authors: Grazia Arpino; Stephanie J. Green; D. Craig Allred; Dannika Lew; Silvana Martino; C. Kent Osborne; Richard M. Elledge
• Keywords: Neoplasms, Hormone-Dependent; Time Factors; Antineoplastic Agents, Hormonal; Receptor, ErbB-2; Gene Amplification; Breast Neoplasms; 3. Good health; ErbB Receptors; Gene Expression Regulation, Neoplastic; Immunoenzyme Techniques; Survival Rate; Tamoxifen; 03 medical and health sciences; Treatment Outcome; 0302 clinical medicine; Premenopause; Receptors, Estrogen; Humans; Female; In Situ Hybridization, Fluorescence; Aged

Abstract Purpose: Preclinical data indicate that expression of the ErbB family receptors, such as HER-2 and HER-1 (EGFR) may be involved in endocrine resistance. Evidence resistance from clinical studies has been inconsistent. The present study examined whether gene amplification or predicted response to tamoxifen. Patients Methods: Three hundred forty nine patients had estrogen receptor (ER)-positive breast cancer received daily tamoxifen initial therapy for advanced disease. amplification, detected by fluorescence situ hybridization, expression, evaluated immunohistochemistry, was determined on 136 204 patients, respectively. Results: correlated with lower ER (P = 0.02), positivity 0.004), protein overexpression < 0.00001). rate 56% non-amplified versus 47% amplified tumors 0.38), 58% HER-1–negative 36% HER-1–positive 0.05). Time treatment failure (TTF) 7 months 5 0.007) tumors, there a trend toward better overall survival (OS) (median 31 25 months, respectively, P 0.07). For positive negative TTF 4 8 0.08) median 24 0.41). Combining status, both longer 0.001) OS 0.03) than if either were positive. In multivariate analysis, not an independent factor OS, although significant only ≤ 0.001). Conclusion: levels modestly less responsive tamoxifen, suggesting molecular events addition those involving receptors are important determining endocrine-resistant phenotype.