A meta-analysis on the interaction between HER-2 expression and response to endocrine treatment in advanced breast cancer

Michele De Laurentiis, Grazia Arpino, Erminia Massarelli, Angela Ruggiero, Chiara Carlomagno, Fortunato Ciardiello, Giampaolo Tortora, Diego D'Agostino, Francesca Caputo, Giuseppe Cancello, Emilia Montagna, Luca Malorni, Luigia Zinno, Rossella Lauria, Angelo Raffaele Bianco, Sabino De Placido

Research output: Contribution to journalArticlepeer-review


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, 1.36-164; 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.

Original languageEnglish
Pages (from-to)4741-4748
Number of pages8
JournalClinical Cancer Research
Issue number13
Publication statusPublished - Jul 1 2005

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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