Conclusion
With the approval of everolimus for metastatic breast cancer patients with acquired endocrine therapy resistance, the first non-ERα-targeted drug that can overcome endocrine therapy resistance has become clinically available. Whether or not inhibitors of the PI3K/Akt/mTOR pathway may overcome endocrine therapy resistance in the adjuvant setting is currently under investigation. A biomarker of an activated PI3K and/or MAPK pathway with clinical validity to predict endocrine therapy resistance in the adjuvant setting has not been identified,
[10] but such a biomarker could potentially be used as a companion diagnostic for these non-ERα-targeted drugs. In our series of ERα-positive postmenopausal breast cancer patients, p-p70S6K is significantly associated with intrinsic tamoxifen resistance. Patients whose tumor expresses p-p70S6K, as a marker of downstream PI3K and/or MAPK pathway activation, have a favorable prognosis but do not benefit from adjuvant tamoxifen. It would be of great importance to validate these findings in other randomized series with endocrine therapy and to further explore this marker as a potential companion diagnostic.
http://www.medscape.com/viewarticle/822167_1