Filippo Montemurro, M.D.
Biomarkers of resitance to endocrine therapy in hormone-receptor positive breast cancer
The efficacy of endocrine therapy, which represents a pivotal treatment for those 70% of women whose breast cancers express hormone-receptors, is limited by primary and acquired resistance mechanisms. Therefore, newer biomarkers that can predict endocrine-responsiveness are eagerly awaited. Our group has recently found that a microRNA (a short sequence of non-coding RNA acting as a post-transcriptional regulator of gene expression) may be implicated in the acquisition of an endocrine-sensitive phenotype in hormone-receptor positive breast cancer cells. Goal: 1) to provide clinical evidence that miR-100 levels predict response to endocrine therapy; 2) to study the prognostic value of miR-100 in patients undergoing surgery for early, hormone-receptor positive breast cancer by comparing levels between patients relapsing and non relapsing within 5 years from diagnosis 3) to identify potential druggable targets for combined treatments in this patient population by studying genes that are regulated by miR-100 and that may be relevant to its role in sustaining and endocrine-sensitive phenotype.
We observed that ectopic expression if miR-100 in breast cancer stem cells derived from hormone-receptor and HER2 negative tumors (basal like) induced loss of stemness features. Furthermore, miR-100 expression induced hormone-receptor expression and sensitivity to endocrine therapy. Finally, low levels of tumor miR-100 were found to predict worse prognosis in four small, independent clinical series of hormone-receptor positive early breast cancer patients (Petrelli A et al. Oncotarget 2015). A phase II pre-surgical study is ongoing and has enrolled 90 of the 180 planned patients. In this study, pre and post-treatment tumor samples will be studied and levels of miR-100 will be correlated with proliferative response. Furthermore, primary tumors from a historical series of 184 patients have been tested for miR-100. Levels of miR-100 will be correlated with prognosis. Extensive gene expression analyses will be carried out to establish signatures of highly endocrine responsive turmors.
Danilo Galizia, M.D.
Elena Geuna, M.D.
Elena Geuna, M.D.