Abstract

The cDNA microarray technology allows the simultaneous analysis of all genes expressed in a tumor. This approach has already permitted to propose a molecular classification of breast cancers. Gene expression profiling is now expected to define prognosis signatures claiming the disease outcome as well as signatures predicting response to therapy. The over-expression of a cluster of genes that are implicated in cell cycle and mitosis control has been shown to discriminate a subgroup of ER+ breast cancers exhibiting a poor prognosis. This "proliferation cluster" is shown to be also present in signatures predicting relapse of ER+ breast cancers treated by the anti-estrogen tamoxifen, including the 36-gene classifier that we have recently identified. Consequently, it seems legitimate to wonder if this part of such predictive signature is really specific to the insensitivity to tamoxifen or rather indicates a poor disease outcome whatever the therapy applied. On the other hand, low expression of ER+ related genes and high expression of genes associated to ER- status or low ERalpha levels have been shown to sign a poor prognosis. Whether the estrogen-related genes that are present in our 36-gene classifier specify the clinical disease outcome or are really specific to the response to tamoxifen, remains to be determined. In any case, the specificity of our 36-gene classifier as those predicting the recurrence of ER+ breast cancer under one treatment or another should be demonstrated. In the same way, future studies should define molecular signatures that will be really predictive of the response to the treatment in order to define which one is the most suitable to decrease the risk of relapse of ER+ breast cancers. These studies should be based on neoadjuvant clinical trials that permit to evaluate the response to treatment in an objective manner.