A Metanalysis on the Interaction between HER2 Expression and Response to Endocrine Treatment in Advanced Breast Cancer

Purpose: Experimental data suggest a complex cross-talk between the HER2 and the estrogen receptor (ER) and it has been hypothesized that HER2+ tumors may be less responsive to certain endocrine treatments. Clinical data, however, have been conflicting. We have conducted a metanalysis on the interaction between the response to endocrine treatment and the overexpression of HER2 in metastatic breast cancer (MBC). Experimental Design: Studies have been identified by searching the Medline, Embase and ASCO abstracts databases. Selection criteria were: a) MBC; b) endocrine therapy (any line of treatment); c) evaluation of HER2 expression (any method). For each study the Relative Risk (RR) for treatment failure for HER2+ over HER2- patients with 95% confidence interval (95%CI) was calculated as an estimate of the predictive effect of HER2. Pooled estimates of the RR were computed by the Mantell-Haenszel method. Results: Twelve studies (n=2,371 patients) were included in the metanalysis: 7 involved tamoxifen (TAM group) and while 5 regarded other endocrine agents (NO TAM group). The overall RR was 1.41 (95%CI=1.32-1.51; P<0.00001; test for heterogeneity: P=0.360) for HER2+ tumors. The RR was 1.36 (95%CI: 1.24-1.50; P<0.00001; test for heterogeneity =0.93) and 1.48 (95%CI: 1.33-1.64; P<0.00001; test for heterogeneity =0.049) in the TAM group and in the NO TAM group, respectively. A second metanalysis limited to tumors that were either ER-positive, ER-unknown or ER-negative/PgR-positive yielded comparable results. Conclusions. HER2+ MBC is less responsive to any type of endocrine treatment. This effect holds in the subgroup of patients with positive or unknown steroid receptors.