RT Dissertation/Thesis T1 El fenotipo "basal-her2" en el cáncer de mama: caracterización clínico-molecular e implicaciones terapéuticas A1 Martín Castillo, María Begoña AB Clinically HER2+ (cHER2+) breast cancer (BC), as exclusively determined by immunohistochemistry of HER2 protein overexpression and/or fluorescence in situ hybridization of HER2 gene amplification, has been largely considered a single disease entity in terms of clinical outcome and in the susceptibility to the anti-HER2 monoclonal antibody trastuzumab (Herceptin). However, although the adjuvant/neoadjuvant use of the trastuzumab has been shown to significantly reduce recurrence risk when added to standard chemotherapy in women with early-stage cHER2+ BC, not all cases derive similar benefit from trastuzumab because a significant number of cHER2+ BC patients develop disease recurrence. Unfortunately, the identification of a robust clinical predictor of trastuzumab benefit, including HER2 itself, has proven challenging in the adjuvant/neoadjuvant setting. Thus, we suggest that a new generation of research needs to refine the prognostic taxonomy of cHER2+ BC and develop easy-to-use, clinicbased prediction algorithms to distinguish between good- and poor- responders to trastuzumab-based therapy ab initio. This study offered two hypotheses: 1.) HER2 overexpression can unexpectedly take place in a molecular background owned by basal-like BC (a commonly HER2-negative BC subtype which possesses many epithelial-mesenchymal transition (EMT) characteristics and exhibits robust cancer stem cell [CSC]-like features), thus generating a so-called basal/cHER2+ BC subtype; 2.) the basal/cHER2+ phenotype confers poor prognosis and delineates a subgroup of intrinsically aggressive cHER2+ BC with primary resistance to trastuzumab... PB Universidad Complutense de Madrid YR 2016 FD 2016-11-18 LK https://hdl.handle.net/20.500.14352/21415 UL https://hdl.handle.net/20.500.14352/21415 LA spa NO Tesis inédita de la Universidad Complutense de Madrid, Facultad de Farmacia, Departamento de Bioquímica y Biología Molecular II, leída el 03-02-2016 DS Docta Complutense RD 15 may 2024