000			nab a22 7a 4500
999			_c16646 _d16646
003			PC16646
005			20211105124216.0
008			211105b xxu||||| |||| 00| 0 eng d
040			_cH12O
041			_aeng
100			_9432 _aManso Sánchez, Luis _eOncología Médica
100			_91804 _aMendiola Fernández, César _eOncología Médica
100			_91082 _aCiruelos Gil, Eva María _eOncología Médica
245	0	4	_aThe Long-HER study: clinical and molecular analysis of patients with HER2+ advanced breast cancer who become long-term survivors with trastuzumab-based therapy. _h[artículo]
260			_bPLoS One, _c2014
300			_a9(10):e109611.
500			_aFormato Vancouver: Gámez Pozo A, Pérez Carrión RM, Manso L, Crespo C, Mendiola C, López Vacas R et al. The Long-HER study: clinical and molecular analysis of patients with HER2+ advanced breast cancer who become long-term survivors with trastuzumab-based therapy. PLoS One. 2014 Oct 20;9(10):e109611.
501			_aPMID: 25330188 PMC4203741
504			_aContiene 48 referencias
520			_aTrastuzumab improves survival outcomes in patients with HER2+ metastatic breast cancer. The Long-Her study was designed to identify clinical and molecular markers that could differentiate long-term survivors from patients having early progression after trastuzumab treatment. Methods: Data were collected from women with HER2-positive metastatic breast cancer treated with trastuzumab that experienced a response or stable disease during at least 3 years. Patients having a progression in the first year of therapy with trastuzumab were used as a control. Genes related with trastuzumab resistance were identified and investigated for network and gene functional interrelation. Models predicting poor response to trastuzumab were constructed and evaluated. Finally, a mutational status analysis of selected genes was performed in HER2 positive breast cancer samples. Results: 103 patients were registered in the Long-HER study, of whom 71 had obtained a durable complete response. Median age was 58 years. Metastatic disease was diagnosed after a median of 24.7 months since primary diagnosis. Metastases were present in the liver (25%), lungs (25%), bones (23%) and soft tissues (23%), with 20% of patients having multiple locations of metastases. Median duration of response was 55 months. The molecular analysis included 35 patients from the group with complete response and 18 patients in a control poor-response group. Absence of trastuzumab as part of adjuvant therapy was the only clinical factor associated with long-term survival. Gene ontology analysis demonstrated that PI3K pathway was associated with poor response to trastuzumab-based therapy: tumours in the control group usually had four or five alterations in this pathway, whereas tumours in the Long-HER group had two alterations at most. Conclusions Trastuzumab may provide a substantial long-term survival benefit in a selected group of patients. Whole genome expression analysis comparing long-term survivors vs. a control group predicted early progression after trastuzumab-based therapy. Multiple alterations in genes related to the PI3K-mTOR pathway seem to be required to confer resistance to this therapy.
710			_9303 _aServicio de Oncología Médica
856			_uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4203741/ _yAcceso libre
942			_2ddc _cART _n0