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A meta-analysis on the interaction between HER-2 expression and response to endocrine treatment in advanced breast
Michele De Laurentiis1, Grazia Arpino, Erminia Massarelli
1Dipartimento di Endocrinologia ed Oncologia Molecolare e Clinica, Università Federico II, Napoli, Italy. michele.delaurentiis@unina.it
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.
Insights
HER-2-positive metastatic breast cancer shows reduced response to endocrine treatments. This finding applies to patients with positive or unknown steroid receptors, impacting treatment strategies.
Area of Science:
- Oncology
- Molecular Biology
- Clinical Research
Background:
- Cross-talk between HER-2 and estrogen receptor suggests HER-2-positive tumors may resist endocrine therapy.
- Clinical data on HER-2 status and endocrine treatment response in metastatic breast cancer are conflicting.
Purpose of the Study:
- To conduct a meta-analysis investigating the interaction between HER-2 overexpression and response to endocrine treatment in metastatic breast cancer.
Main Methods:
- Systematic literature search of Medline, Embase, and ASCO databases.
- Inclusion criteria: metastatic breast cancer, any endocrine therapy, HER-2 expression evaluation.
- Calculated pooled relative risk for treatment failure in HER-2-positive vs. HER-2-negative patients using Mantel-Haenszel method.
Main Results:
- Included 12 studies with 2,379 patients.
- Overall relative risk of treatment failure for HER-2-positive tumors was 1.42 (95% CI, 1.32-1.52).
- Pooled relative risks for tamoxifen (1.33) and other hormonal drugs (1.49) were significant; heterogeneity was low.
Conclusions:
- HER-2-positive metastatic breast cancer exhibits diminished responsiveness to all types of endocrine treatment.
- This reduced responsiveness is consistent in patients with positive or unknown steroid receptors.