A Meta-Analysis on the Interaction between HER-2 Expression and Response to Endocrine Treatment in Advanced Breast Cancer

• Published in: Clinical cancer research 2005-07, Vol.11 (13), p.4741-4748
• Main Authors: De Laurentiis, Michele, Arpino, Grazia, Massarelli, Erminia, Ruggiero, Angela, Carlomagno, Chiara, Ciardiello, Fortunato, Tortora, Giampaolo, D'Agostino, Diego, Caputo, Francesca, Cancello, Giuseppe, Montagna, Emilia, Malorni, Luca, Zinno, Luigia, Lauria, Rossella, Bianco, Angelo Raffaele, De Placido, Sabino
• Format: Article
• Language: English
• Subjects: Antineoplastic Agents, Hormonal - therapeutic use; Breast Neoplasms - drug therapy; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Female; Growth factors; Humans; Metastatic breast cancer; Predictive factors; Receptor, ErbB-2 - metabolism; Receptors, Estrogen - analysis; Receptors, Progesterone - analysis; Tamoxifen - therapeutic use; Treatment Outcome
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1078-0432.CCR-04-2569

Purpose: Experimental data suggest a complex cross-talk between HER-2 and estrogen receptor, and it has been hypothesized that HER-2-positive tumors may be less responsive to certain endocrine treatments. Clinical data, however, have been conflicting. We have conducted a meta-analysis on the interaction between the response to endocrine treatment and the overexpression of HER-2 in metastatic breast cancer. Experimental Design: Studies have been identified by searching the Medline, Embase, and American Society of Clinical Oncology abstract databases. Selection criteria were ( a ) metastatic breast cancer, ( b ) endocrine therapy (any line of treatment), and ( c ) evaluation of HER-2 expression (any method). For each study, the relative risk for treatment failure for HER-2-positive over HER-2-negative patients with 95% confidence interval was calculated as an estimate of the predictive effect of HER-2. Pooled estimates of the relative risk were computed by the Mantel-Haenszel method. Results: Twelve studies ( n = 2,379 patients) were included in the meta-analysis. The overall relative risk was 1.42 (95% confidence interval, 1.32-1.52; P < 0.00001; test for heterogeneity = 0.380). For studies involving tamoxifen, the pooled relative risk was 1.33 (95% confidence interval, 1.20-1.48; P < 0.00001; test for heterogeneity = 0.97); for studies involving other hormonal drugs, a pooled relative risk of 1.49 (95% confidence interval, 1.36-1.64; P < 0.00001; test for heterogeneity = 0.08) was estimated. A second meta-analysis limited to tumors that were either estrogen receptor positive, estrogen receptor unknown, or estrogen receptor negative/progesterone receptor positive yielded comparable results. Conclusions: HER-2-positive metastatic breast cancer is less responsive to any type of endocrine treatment. This effect holds in the subgroup of patients with positive or unknown steroid receptors.