Referee 2's review:

This paper suggested the functional interaction between alpha6-beta4 and ErbB-3 to Tam resistance in the absence of ER-beta1 in breast cancers. Activation of AKT by phosphorylation was caused by alpha6-beta4 through ErbB-3 protein regulation. Inhibition of ErbB3 activition abrogated AKT phosphorylation, induce apoptosis and inhibits in vitro invasion favoring Tam responsiveness. Proper statistical methods were applied and described in detail. ErbB3, p-AKT, and ER-beta1 were found significantly associated with disease free survival. Analysis on other clinical parameters was also addressed. Their findings can be further developed and used for future therapeutic management on breast cancers.

Comments:
Authors claimed that they have used a "large panel" of human breast cancer cell lines in their study, but there were five cell lines. This will mislead the readers.

It seems that there are two systems for quantification analysis on PR, ERa and ER-beta1 immunohistochemistry (cutoff: 10% for both PR and ERa, and 20% for ER-beta1). What is the reasoning? Why use 20% as a cut-off for ER-beta1?

Control tissue section has not been included in immunohistochemistry to control staining intensity on each antibody. Staining varies significantly if there is no control tissue section in each batch of experiment.

How specific of the primers is to the transcript of ER-beta1? Splicing variants of ER-beta have been demonstrated to have different effect to the cancer cells (Treeck O et al Breast Cancer Res Treat. 2007 and others). The elevated expression of other ER-beta variants should be examined as well.

Gene expression analysis was examined by different assays in this study, what are the correlations of the results between these assays? Are they consistent?

Explanation of some notations and abbreviations are missing in the text and figures, such as LM5, scr, B3si, etc.

Result of invasion experiments was summarized in Figure 3. Authors should also display an illustration of the stained cells in the wells and chambers so that one can assess their experimental results.

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N.B. These are the comments made by the referee when reviewing an earlier version of this paper. Prior to publication the manuscript has been revised in light of these comments and to address other editorial requirements.