352P - mTOR expression in basal-like breast cancer and the ability of everolimus to inhibit the invasion cancer cell capacity

Date 29 September 2012
Event ESMO Congress 2012
Session Poster presentation I
Topics Breast Cancer, Locally Advanced
Translational Research
Presenter Diana Martins
Authors D.F. Martins, B. Sousa, J. Paredes, F. Schmitt
  • Cancer Genetics- Breast Pathology, Institute of Molecular Pathology and Immunology of the University of Porto, IPATIMUP, University of Porto, 4200-465 - Porto/PT

Abstract

The introduction of high-throughput technologies in breast cancer enabled the recognition of groups with prognostic value, in which target-therapies can be applied. However, a relevant percentage of patients show no clinical benefit or incur in the development of acquired resistance. A possible solution could be the inhibition of pathways that are common in all tumor subtypes that have a proven role in carcinogenesis. Alterations of the serine-threonine kinase mammalian target of rapamycin (mTOR) signaling pathway are common in cancer and thus mTOR is being pursued as a therapeutic agent. Everolimus, a rapamycin analog, has already an established activity in the treatment of renal cell carcinoma. In this study, we proposed to evaluate the expression of activated mTOR in a large series of invasive carcinoma samples and cell lines, and its association with the four main molecular subtypes (Luminal A, Luminal B, HER2-overexpressing and Basal-like). We also aimed to evaluate the ability of Everolimus to inhibit mTOR expression and function in breast cancer cells. p-mTOR expression was found in 66.7% (231/348) of the invasive breast carcinoma cases analysed. Considering the molecular subtypes of breast carcinomas, p-mTOR was more frequently observed in basal-like breast carcinomas (80.6%). All breast cancer cell lines, representative of distinct molecular subtypes, showed expression of total and activated mTOR. These cells have been treated with RAD001, in order to assess their sensitivity to this drug, and all cell lines showed a decrease of p-mTOR expression after everolimus treatment. Due to the higher prevalence of p-mTOR in basal-like tumors, we treated three basal-like cell lines with Everolimus to assess the effects on cell invasion and aggregation. Cell invasion was significantly inhibited in response to Everolimus. The results revealed that there is a significant higher frequency of p-mTOR in basal-like tumors, compared with the other subtypes. In addition, Everolimus is able to significantly decrease mTOR expression and activity, inhibiting invasion capacity of basal-like breast cancer cells emphasizing the antitumour activity of mTOR inhibitors in breast cancer models.

Disclosure

All authors have declared no conflicts of interest.